Yarmohammadi-Samani Et Al

NEUROSCIENCE
RESEARCH ARTICLE
P. Yarmohammadi-Samani et al. / Neuroscience 480 (2022) 79–96
Long-lasting Postnatal Sensory Deprivation Alters Dendritic

Morphology of Pyramidal Neurons in the Rat Hippocampus: Behavioral
Correlates
Parisa Yarmohammadi-Samani, Hamid Taghipourbibalan y and Jafar Vatanparast *
Department of Biology, School of Science, Shiraz University, Iran
Abstract—The role of normal sensory inputs in the development of sensory cortices is well known, however, their
impacts on the hippocampus, an integrator of sensory modalities with important roles in cognitive functions, has
received much less attention. Here, we applied a long-term sensory deprivation paradigm by trimming the rats’
whiskers bilaterally, from postnatal day 3 to 59. Female sensory-deprived (SD) rats showed more on-wall rearing
and visits to the center of the open-field box, shorter periods of grooming, less defecation and less anxiety-like
behaviors in the elevated plus-maze compared to controls, who had their intact whiskers brushed. Passive avoid-
ance memory retention was sex-dependently impaired in the female SD rats. In the radial arm maze, however, ref-
erence spatial memory was impaired only in the male SD rats. Nonetheless, working memory errors increased in
both sexes of SD rats. Besides depletion of CA1 and CA3 pyramidal neurons in SD rats, Sholl analysis of Golgi-
Cox stained neurons revealed that prolonged sensory deprivation has retracted the arborization of CA1 basal
dendrites in SD group, while solely female SD rats had diminished CA1 apical dendrites. Sholl analysis of CA3
neurons in SD animals also disclosed significantly more branched apical dendrites in males and basal dendrites
in females. Sensory deprivation also led to a considerable spine loss and variation of different spine types in a
sex-dependent manner. Our findings suggest that experience-dependent structural plasticity is capable of
spreading far beyond the manipulated sensory zones and the inevitable functional alterations can be expressed
in a multifactorial sex-dependent manner. Ó 2021 IBRO. Published by Elsevier Ltd. All rights reserved.
Key words: barrel-cortex sensory deprivation, hippocampus, pyramidal neurons, dendritic morphology, memory, anxiety.
INTRODUCTION tional deficits. These alterations are not restricted to the

deprived cerebral cortex but have also been traced in
An essential and basic feature of the neural system is its the non-deprived cortical areas involved in other senses,
plasticity, the ability to change the structure and/or a phenomenon called cross-modal neuroplasticity. A
function of neurons in response to experience and compensatory increase in the performance of cortical
learning. Early life sensory experiences are especially regions processing the remaining intact senses and the
necessary for the normal development of the brain due recruitment of the deprived region for other spared
to their crucial role in the structural and functional senses through rewiring of the brain connections are con-
plasticity of neurons that determine the proper formation sidered as the best-known features of cross-modal plas-
of neuronal circuitries and activity (Wiesel and Hubel, ticity (Rauschecker, 1995; Merabet and Pascual-Leone,
1963; Breton and Stuart, 2009; Chen et al., 2015; Ueno 2010). In spite of numerous reports on the effects of sen-
et al., 2015; Zhang et al., 2016). Sensory deprivation dur- sory deprivation on the structure and function of neurons
ing early life can induce lasting behavioral impairments. within sensory regions, either deprived or non-deprived,
Alterations in the structure and function of cortical neu- very little is known about the effects on the neurons
rons have been implicated in such cognitive and emo- beyond the sensory regions. If sensory deprivation could
have indirect effects on non-deprived cortical regions,
*Corresponding author. Address: Department of Biology, School of brain areas beyond sensory cortices that indirectly
Science, University of Shiraz, Shiraz, Iran. receive sensory information can be affected by sensory
E-mail addresses: [email protected], jvatanparast@gmail. deprivation. The fact that sensory deprivation induces
com (J. Vatanparast).
y various cognitive and emotional changes, also support
Present address: Behavioral and Translational Neuroscience
Group, Department of Psychology, Faculty of Health Sciences, UiT the assumption that the structural and functional alter-
The Arctic University of Norway, Tromsø, Norway. ations induced by sensory deprivation may extend to
Abbreviations: ANOVA, analysis of variance; fSTL, first step-through non-sensory areas of the brain.
latency; PND, postnatal day; SD, sensory-deprived.
https://doi.org/10.1016/j.neuroscience.2021.11.011
0306-4522/Ó 2021 IBRO. Published by Elsevier Ltd. All rights reserved.
79
80 P. Yarmohammadi-Samani et al. / Neuroscience 480 (2022) 79–96
Hippocampus is an allocortical structure with crucial for morphological experiments. Only one data point per
roles in spatial representation and consolidation of animal was obtained in each experiment and used for
declarative memories (Eichenbaum and Cohen, 2014). statistical analysis.
It indirectly receives inputs from different sensory cortices,
including the somatosensory cortex, mainly through its Behavioral tests
tight connections to the entorhinal cortex (Liu et al.,
2018). The fact that hippocampal place cells fire only From PND 67 rats were subjected to a battery of
when animal receives multi-modal sensory cues of a par- behavioral tests including open field, elevated plus
ticular place is a well-known example that shows sensory maze, eight arms radial maze and passive avoidance
inputs are critical for the function of hippocampus (Fig. 1). The equipment used for behavioral tests were
(O’Keefe, 1976). Environmental enrichment also cleaned with a damp paper towel after each trial to
increases the dendritic complexity and spine density in remove residual odors. All behavioral tests were
hippocampal neurons (Rampon et al., 2000; Van Praag conducted during the light phase between 10:00–14:00.
et al., 2000; Faherty et al., 2003). CA1 and CA3 pyramidal The rats were moved to the adjacent test room 30 min
neurons are the main principal neurons of the hippocam- before the experiment starts. To reduce the behaviors
pus and also the source of major hippocampal outputs driven by olfactory cues, the floor and the walls of the
(Graves et al., 2012). In many studies strong correlation testing devices were cleaned by mild detergent between
between structural alterations in CA1 and CA3 subfields trials for rats from the same homecage and wiped with
and behavioral deficits have been reported (Soetanto 70% ethanol for rats of different sex.
et al., 2010; Morales-Medina et al., 2013; Bencsik et al.,
2019). Despite several reports on the influences of Open field
enhanced sensory inputs on the structure of neurons in
the hippocampus, surprisingly, there is no comprehen- The Open-Field chamber was a custom-made
sively decisive report about the effects of sensory depriva- 40 40 40 cm opaque plexiglas box evenly
tion on neuronal structures in the hippocampus, and their illuminated from the top and a camera was installed
potential correlations with behavioral outcomes. These above the chamber on a tripod to record the animal’s
issues are the main focus of the current study. activity for subsequent manual analysis. The floor of the
chamber was divided into four equal squares by distinct
marker lines. The center of the arena was determined
EXPERIMENTAL PROCEDURES as the ¼ inner part of the floor also marked with dashes
Animals representing a smaller square. Rat were individually
placed at a designated corner of the box and their
All procedures were performed in accordance with the activity was recoded for 5 min.
National Institute of Health Guide for the Care and Use The total number of line crossings (square crossing)
of Laboratory Animals and were approved by the local was considered as the locomotor activity. Each time all
animal ethics committee at Shiraz University. All efforts four paws of the animal crossed the lines as the animal
were made to minimize the number of animals used and entered the adjacent square either horizontally or
their suffering. Male and female Wistar rats from our diagonally, one movement was registered. A rearing
breeding colony were kept in a well-ventilated room at gesture was scored whenever the rat took a fully upright
22 ± 2 °C with a 12 h light–dark cycle and free access posture by standing on its hind limbs. This behavioral
to food and water, unless otherwise mentioned. On the activity was further featured by on-wall rearing in which
day after birth (postnatal day1, PND1), litters were the rat stood fully upright with taking the aid of the walls,
culled to seven or eight pups with an equal number of and off-wall rearing in which the rat took an upright
males and females, whenever possible. Litters were positon in the open air without any wall support. Time
randomly allocated into the treatment and control spent in the central square, either by standing still or
groups. In the treatment group, the whiskers were passing through, and the total time spent on grooming
trimmed bilaterally to less than 1 mm every other day were registered by a stopwatch. The animal was
from PND 3 to PND 59. Animals in the control group considered in a grooming state if stood still showing
were similarly handled and their whiskers were gently stereotypical behaviors such as licking paws or body
brushed with scissors to mimic the stimulation that rats and stroking face and ears. The number of fecal boli
in the treatment group received during whisker trimming. was counted at the end of each trial.
Animals were weaned on PND 23, separated by sex on
PND 40 and maintained three to four per cage until the
Elevated plus maze
day of experiment. All animals within a litter were
assigned to the same group but no more than one male The elevated plus maze consisted of two opposite closed
and one female rat from each litter were used per arms (50 cm long 10 cm wide 40 cm height)
experimental group. Other animals in each litter were alternating at right angles with two open arms (50 cm
used for other experiments (for either this or other long 10 cm wide) made of gray PVC and was kept
projects). The number of animals for each experiment 60 cm above the floor by a metal pedestal (Borj Sanat
was determined according to the estimate of the Co., Tehran, Iran). Illumination was provided by a red-
standard deviation of the results. Therefore, the sample tinted bulb lamp positioned about 1.5 m above and
size is generally larger for behavioral experiments than oblique to the maze to provide a dim light not directly
P. Yarmohammadi-Samani et al. / Neuroscience 480 (2022) 79–96 81
illuminating the closed arms and not exposing the open were recorded by a video camera from the side of the
arms with high lux intensity. Each rat was placed in the maze for subsequent analysis. An arm entry was
central platform facing an open arm and allowed to recorded when all paws entered an arm. The first entry
freely explore the maze for 5 min. The trial was into an unbaited arm was recorded as a reference mem-
recorded by an overhead camera and the number of ory error. Secondary efforts to an unbaited arm and sub-
entrances and the time spent in the closed and open sequent entries into already visited baited arms during a
arms were scored off-line. training session were defined as working memory error.
Radial arm maze Passive avoidance test

The radial maze consisted of eight arms (65 cm The passive avoidance apparatus consisted of an
long 10 cm wide with 17 cm side walls) extending illuminated and a dark compartment of the same size
radially from an octagonal central hub (32 cm in (20 cm 20 cm 30 cm) adjoining each other through
diameter). The apparatus floor was made of opaque a guillotine door. Floors were constructed of 3 mm
gray PVC and the side walls were made of transparent stainless steel rods spaced 1 cm apart. The floor of the
plexiglas. The maze was supported by a metal frame dark chamber was connected to a stimulator so that
40 cm above the floor in a quiet room containing several could be electrified by intermittent electric pulses.
visual cues external to the maze. A food cup Illumination inside the lighted chamber was provided by
(5 cm 5 cm and 2.5 cm deep) was placed near the a 60 W lamp 40 cm above the chamber.
distal end of each arm and peanut halves were used as The passive avoidance test was conducted as
food reward. The task was performed as described described earlier (Vatanparast et al., 2013). In brief, rats
earlier (Alipour et al., 2019). In brief, the diet of rats was were given two trials to habituate to the apparatus. Each
reduced for a week to keep their body weight at approxi- animal was gently placed in the illuminated compartment
mately 90% of free-feeding level. The test was performed facing away from the dark compartment. After 10 s the
in shaping and training phases. Two sessions of social guillotine door was raised and the animal was allowed
shaping and two sessions of individual shaping were con- to enter the dark compartment. Entrance latency into
ducted in four consecutive days to familiarize rats with the the dark compartment (first step-through latency, fSTL)
apparatus and the food reward. During social shaping, was recorded when the animal had placed all four paws
three rats were placed in the maze and gained access into the dark compartment. If the animal waited for more
to arms and peanut halves, which were scattered than100s to enter the dark compartment, it was excluded
throughout all arms. Animals were removed as soon as from the experiment. Upon entering the dark compart-
peanuts were eaten or 10 min had elapsed. In individual ment, the door was closed and 30 s later the rats were
shaping sessions, each rat was allowed 5 min to explore taken from the dark compartment into their home cage.
the maze with all eight arms baited. In each day of shap- The trial was repeated after 30 min and followed after
ing, peanuts were placed further distal into each arm until the same interval by the acquisition trial during which a
they were finally placed at food cups. Rats were then 0.6 mA, 50 Hz unavoidable foot-shock was applied for
trained for 12 sessions, once per day. At the beginning 2.5 s when the rat entered into the dark compartment after
of each training session four arms were baited and the the animal had entered the dark compartment and the
other four arms were left unbaited. The pattern of baited guillotine door was closed. After 30 s the animal was
and unbaited arms was consistent among rats and removed from the apparatus and placed into the home
throughout testing and no more than two consecutive cage. Two minutes later, the animal was placed again
arms were left unbaited. Each trial began by placing the inside the illuminated compartment, and if the animal
rat in the opaque cylinder on the central platform for refrained entering the dark compartment during the
10 s. The cylinder was then removed and the rat was 120 s of the session it was considered to reach the learn-
allowed to explore the maze and to eat peanuts. The trial ing criterion. Otherwise, by entering the dark compart-
was terminated and the animal was removed as soon as ment (before120s), the door was closed and the animal
all peanut halves were eaten or 5 min had elapsed. Con- received the same shock again. The acquisition of PA
sidering the involvement of the cholinergic system in sen- was tested again after 2 min and animal received a foot-
sory processing (Eggermann et al., 2014), learning/ shock each time entered the dark compartment. The
memory and attention (Teles-Grilo Ruivo and Mellor, training was terminated when the rat remained in the light
2013), and previous reports addressing the interactions compartment for 120 consecutive seconds. The number
of sensory deprivation and cholinergic modulation on the of trials (entries into the dark chamber) was recorded as
structural plasticity on neurons (Schliebs et al., 1982; an index of task acquisition and short-term memory.
Maurer and Williams, 2017), following the 12 sessions The retention test was performed twenty-four hours
of radial maze training, rats were trained for four more after the training session. Each animal was placed in
days in which they were challenged with two doses of the light chamber for 10 s, the guillotine door was
muscarinic acetylcholine receptor antagonist, scopo- raised, and the STL and the time spent in the dark
lamine. Rats received i.p. injections of scopolamine (0.1 compartment (TDC) were recorded up to 300 s. If the
and 0.2 mg/kg) or 0.9% saline as vehicle (1 ml/kg) rat did not enter the dark compartment within 300 s, the
30 min before the start of each radial arm maze session. retention test was terminated and a ceiling score of
Two non-drugged (vehicle) days were inserted between 300 s was assigned to STL. During the retention
drugged sessions for drug washout. The training sessions sessions, no electric shock was applied.
Golgi-cox staining (http://research.ssm.edu/cnic/tools-ns.html), and spines

were classified as mushroom, stubby and thin,
Golgi-Cox staining was performed according to the
according to (Peters and Kaiserman-Abramof, 1970)
protocol suggested by (Das et al., 2013) and (Ranjan
and were manually corrected.
et al., 2014) with slight modifications. Deeply anesthetized
rats were perfused with normal saline and the brains were
removed and each brain was cut into 5–8 mm coronal Cresyl Violet staining
blocks containing the dorsal hippocampus. Brain blocks Rats were deeply anesthetized and perfused with normal
were placed in dark colored bottles containing freshly pre- saline followed by 4% paraformaldehyde in phosphate-
pared Golgi-Cox (5% potassium dichromate solution, 5% buffered saline. The brain tissue was post-fixed at 4 °C
mercuric chloride, 5% potassium chromate and distilled in the same fixative. Paraffin-embedded blocks of brain
water in the ratio 5:5:4:10) and stored in dark at 37 °C were serially sectioned in coronal plane (5-mm-thick)
for 24 h. The blocks were then transferred to 30% sucrose using a microtome. The sections were deparaffinized,
solution at 4 °C for 8 h, and then placed in fresh 30 % stained with Cresyl Violet, dehydrated, cleaned and
sucrose solution at 4 °C for 3–7 days. 120 lm thick coro- mounted on slides. The stained pyramidal neurons were
nal sections were cut using vibratome, collected in 6% counted in hippocampal CA1 and CA3 subfields by
sucrose solution and transferred to gelatin-coated slides. using a ruled graticule eyepiece in a total area of
Slides were then washed in distilled water, immersed in 0.063 mm2. Digitized images of hippocampal neurons in
75% ammonium hydroxide for 10 min, washed and then CA1 and CA3 regions were captured using a Nikon light
immersed in 1% sodium thiosulfate for 10 min in dark. microscope.
Slides were washed and dehydrated with serial dilutions
of alcohol and finally kept in a solution of chloroform, Statistical analysis
xylene and 100% alcohol (ratio 1:1:1) for 4 min. The sec-
tions were cleaned for 4 min with xylene and left in fresh The Shapiro–Wilk normality test was used to assess the
xylene for 1 h in the dark. Slides were then mounted in normal distribution of data. Homogeneity of variances
Entellan, and visualized under a bright field microscope was confirmed by Leven test. Two-way fixed effect
at 10x/0.25 and 100x/1.25 oil-immersion objective (Nikon analysis of variance (ANOVA) followed by Tukey’s post
Eclipse 80i microscope connected to a Nikon DS-Fi1 dig- hoc test was used to compare groups with normally
ital camera) for studying dendrite branching and dendritic- distributed variables. When data were not normally
spine morphology, respectively. distributed, Kruskal-Wallis test followed by Dunn’s test
was used. Following Tukey or Dunn tests, p values
were adjusted for multiple comparisons. To detect the
Imaging, Sholl and spine analysis possible interactions between treatment and sex, an
Pyramidal neurons of the dorsal CA1 and CA3 initial ANOVA was run. When a significant interaction
hippocampal subregions (plates 57–60 of Paxinos and was found between treatment and sex, the data set was
Watson, 2006) were selected for this study. The following divided by sex and the analysis was done separately on
criteria were used to select pyramidal neurons in the hip- the subdivisions. Otherwise, the data for males and
pocampus: (1) their triangle-shaped soma, (2) complete females were combined and comparisons between
dendrites without apparent truncation, (3) the presence control and SD groups were done using unpaired t-test
of at least one apical and two primary basilar dendrites or Mann-Whitney U test depending on the normality of
that branched at least once, (4) the cell soma location the distribution.
must be in the dorsal CA3 and CA1 hippocampal subre- The accepted level of significance for main treatment
gions. Estimates of total dendritic length, branch order effects was p < 0.05 and for interactions was p < 0.1.
and soma area were obtained from a total of 271 (137
CA1 and 134 CA3) neurons in the dorsal hippocampus RESULTS
(6–8 animals per sex in each group and 7–10 neurons
Open field test
per animal). Images of the neurons were captured using
a Nikon Eclipse 80i microscope connected to a Nikon Whisker trimming during PND 3-PND 59 significantly
DS-Fi1 digital camera. Analysis of the images was per- increased the time spent in the center zone of the maze
formed using the NeuronJ plugin in ImageJ software (unpaired t-test; t94 = 2.74, p < 0.01), but did not affect
(Rasband, W.S., ImageJ, US National Institutes of Health, line crossing score and off-wall rearing. These
Bethesda, Maryland, USA, http://imagej.nih.gov/ij/, 1997– parameters did not show significant interactions with
2012), NeuronStudio, and Bonfire scripts in MATLAB soft- sex, so data from male and female rats were pooled
ware (Kutzing et al., 2010; Langhammer et al., 2010). within each group. Kruskal-Wallis test revealed
For spine analysis, 3–5 neuron and 3 apical and 3 significant difference between groups in on-wall rearing
basal second- or third-order segments per rat (with 3–5 (H3 = 21.8, p < 0.001), time spent in self-grooming
rat from every sex per group) that were 20 lm in length (H3 = 26.9, p < 0.001) and number of fecal boli
and originated at least 40 lm from the soma were (H3 = 8.5, p < 0.05). Post hoc pairwise comparisons
traced in bright-field images. We used the ImageJ showed more frequent on-wall rearing (Dunn’s test;
software for obtaining a detailed morphometric profile of Z = 2.76, p < 0.05), reduced fecal boli counts (Dunn’s
spines. Then, analysis of images was performed using test; Z = 2.7, p < 0.05) and the time spent on self-
the semi-automated Spine Classifier of NeuronStudio grooming (Dunn’s test; Z = 2.65, p < 0.05) in SD
male and female rats in the reference memory that

normally expected in the radial arm maze test. Sensory
deprivation also increased working memory errors in
both male and female rats, but this effect was more
pronounced in female rats and, as a result, exaggerated
the difference in the working memory between male and
female rats (Fig. 6).
Fig. 1. Schematic of the experimental timeline. At the end of these
experiments, the remaining animals were used for other studies (not Analysis of data obtained on the drug challenge
presented here). experiments using Kruskal-Wallis tests showed
significant difference between groups in reference
memory errors (H11 = 68.2, p < 0.001) and working
female rats compared to control female rats but not in the memory errors (H11 = 102.4, p < 0.001). Post hoc
male rats. While the time spent on self-grooming was not pairwise comparisons showed that higher dose of
different between male and female control rats, this time scopolamine (0.2 mg/kg) significantly increased the
was dramatically longer in SD females compared to SD number of reference memory errors in male (Dunn’s
male rats (Dunn’s test; Z = 5.11, p < 0.001) (Fig. 2). test; Z = 3.5, p < 0.05) and female (Dunn’s test;
Z = 4.32, p < 0.01) control rats. In sensory-deprived
Elevated plus maze rats, the lower dose also significantly increased
reference memory errors in male rats compared to their
Analysis of data obtained on the elevated plus maze using
sex matched controls that received the same dose of
ANOVA and Kruskal-Wallis tests showed significant
scopolamine (Dunn’s test; Z = 3.4, p < 0.05).
difference between groups in percentage of open arm
Following the injection of the higher dose of
entries (H3 = 12.3, p < 0.01), percentage of time spent
scopolamine, the number of reference memory errors in
in the open arms (H3 = 11.9, p < 0.01), number of
the sensory-deprived female rats was significantly lower
closed arm returns (H3 = 16.2, p < 0.01) and the time
than control female rats that received the same drug
spent in the center square (F3,87 = 3.4, p < 0.05). Post
(Dunn’s test; Z = 3.38, p < 0.05). The lower dose of
hoc multiple comparisons showed that postnatal whisker
scopolamine significantly increased working memory
deprivation did not significantly affect the performance of
errors only in the control male rats (Dunn’s test;
male rats in the elevated plus maze. On the other hand,
Z = 3.38, p < 0.05), while the dose of scopolamine
female rats in the SD group showed higher percentage
increased working memory errors in both male (Dunn’s
of open arm entries (Dunn’s test; Z = 2.65, p < 0.05),
test; Z = 3.64, p < 0.05) and female control rats, with
percentage of time spent in the open arms (Dunn’s test;
a more pronounced effect in female rats (Dunn’s test;
Z = 2.74, p < 0.05), number of closed arm returns
Z = 4.7, p < 0.001). Both doses of scopolamine
(Dunn’s test; Z = 3.25, p < 0.01) and the time spent in
increased working memory errors in a dose dependent
the center square (Tukey’s post hoc test; q = 4.44,
manner in male SD rats, but in female SD rats only the
p < 0.05) compared to the sex-matched controls (Fig. 3).
higher dose showed a significant effect. The effects of
scopolamine on the number of working memory errors
Passive avoidance test
were not significantly different between control and SD
During the acquisition trial, the number of shocks required rats in either males or females (Fig. 7).
for learning the task was not significantly different
between sensory deprived and control rats (Mann- Neuronal morphology, dendritic spine properties and
Whitney U test; U44,48 = 582, p = 0.45). On the other density of pyramidal neurons in CA1 and CA3
hand, Kruskal-Wallis test revealed significant difference hippocampal subfields
between groups in STL (H3 = 22.8, p < 0.001). Post
hoc pairwise comparisons showed that female rats in Golgi staining was used to visualize individual pyramidal
the SD group represent significantly shorter STLs neurons in the CA1 and CA3 subfields of the
compared to control females (Dunn’s test; Z = 2.76, hippocampus. The dendritic morphology of the neurons
p < 0.05). In control rats, the mean STL was not of adult rats (PND 60) from control and sensory
significantly different between male and female rats, but deprived groups were quantified using Sholl analysis.
SD female rats showed significantly shorter STLs Whisker deprivation did not affect apical dendrites of
compared to SD male rats (Dunn’s test; Z = 4.59, CA1 neurons in male rats but significantly reduced total
p < 0.001) (Fig. 4). dendritic length, number of branch points and terminal
points of basal dendrites. Statistical analysis also
revealed a significant decrease of Sholl intersections in
Spatial memory in the radial arm maze
proximal (<60 lm from the soma periphery),
Control animals showed sex differences in the radial intermediate (60–120 lm from the soma periphery) and
maze task, with males committing fewer reference and distal (>120 lm from the soma periphery) segments of
working memory errors (Figs. 5C, 6D). Sensory the basal dendrites of CA1 neurons in male SD rats
deprivation did not significantly affect the number of compared to naive male rats (Fig. 8). In female rats, the
reference memory errors in female rats, but increased total length of apical dendrites of CA1 neurons was
reference memory errors in males. Prolonged postnatal shorter than males in both control and SD groups, but
sensory deprivation eliminated the difference between there was not a significant difference between control
A D 100 Sholl intersections was detected

50 in the proximal (<120 lm from
the soma periphery) apical
###
40 dendrites of CA1 neurons in SD
Line crossings
Grooming (s)
female rats, but intermediate
(120–240 lm from the soma
30 periphery) and distal (>240 lm
50 from the soma periphery) apical
20 dendrites were not significantly
affected by sensory deprivation
10 * (Fig. 8C). Significant reduction of

Sholl intersections was observed
in proximal and intermediate basal
0 0 dendrites of CA1 neurons of SD
Control SD Male Female female rats, but this effect did not
B E reach significance level for the
80 6 majority of distal portions of basal
Control dendrites. Male control rats had
Time in the center (s)
** SD more Sholl intersections in the

distal segment of apical and
60
Fecal boli
4 intermediate segment of basal

dendrites of CA1 neurons
40 compared to female control rats.
In the SD group, the lower
2 dendritic arborization of female
rats compared to males was
20
* mainly in the intermediate range.
The difference between male and
female rats in the number of Sholl
0 0 intersections was reduced in the
Control SD Male Female
SD compared to the control
C F group, which was more evident in
##
30 40 the intermediate segment
(Fig. 8C, D).
* Representative Golgi-stained
Off-wall rearing
On-wall rearing
30 CA3 neurons of male and female

rats from control and SD rats
20
have been shown in Fig. 9A.
Apical dendrites of CA3 neurons
20
in female control rats showed
* significantly more branch points
10 compared to control males, while
10 total dendritic length and number
of branch points in the basal
dendrite of CA3 neurons in female
0 0 control rats were significantly
Control SD Male Female
lower than those in male rats
Fig. 2. Effects of sensory deprivation on the performance in the open field test. Total line crossing (A), (Fig. 9B). Long-term postnatal
time spent in the central area (B), number of off-wall rearing (C), time spent on self-grooming (D), the whisker deprivation increased
number of fecal boli (E) and number of on-wall rearing (F). Box diagrams show interquartile range, apical dendrites of CA3 neurons
horizontal lines are median and whiskers represent 5th and 95th percentiles. Outliers are data outside in young adult male rats, but not
5th to 95th percentile. In (A–C) the interaction with sex was not significant and data were pooled for
both sexes (n = 46–50 per group of both sexes). In (D–F) significant interaction of treatment sex
in the SD female rats. Male rats
was detected and data were analyzed separately for each sex (n = 22–27 per sex in each group). from control group showed more
*p < 0.05 compared to control female rats, **p < 0.01 compared to control group. ##p < 0.01 and dendritic intersection in the
###p < 0.001 compared to male rats in the same group. SD: sensory-deprived. proximal range of CA3 apical
dendrites while female control rats
had more dendritic arborization in
and SD female rats for this variable. SD female rats also
the intermediate dendrite segments (Fig. 9C). Basal
had significantly fewer branch points and terminal points
dendrites of CA3 neurons in male SD rats showed
in the apical dendrites of CA1 neurons compared to the
reduced Sholl intersections in the proximal and
sex-matched controls (Fig. 8B). Significant decrease of
A C intermediate ranges, while in

60 Control 30 female SD rats, basal dendrites of
Time in open arms (%)
SD
Closed arm returens

CA3 neurons showed increased
Sholl intersections in all dendritic
segments, especially in distal
40 * 20 ** portion. In the control group, male
rats had CA3 neurons with more
intermediate and distal basal
dendrite arborization compared to
20 10
females, but the sex difference
was not detected between CA3
neurons of male and female rats
0 0 in the SD group (Fig. 9D).
Male Female Male Female Basal and apical dendritic
B D spine densities were measured in
Entries into open arms (%)
60 100 CA1 and CA3 pyramidal neurons

of control and sensory-deprived
80
* rats. Our results showed that
Center time (s)
40
* whisker deprivation led to a
significant decrease in spine
60
density on both apical and basal
dendrites of CA1 and CA3
40 pyramidal neurons in female rats.
20
Sensory deprivation also
20 significantly decreased the density
of dendritic spines on the apical
0 0 dendrites of CA3 pyramidal
Male Female Male Female neurons and on the basal
dendrites of CA1 pyramidal
Fig. 3. Effects of sensory deprivation on the performance in elevated plus maze test. The time spent neurons of male rats. Examining
in the open arms (A), number of entries into open arms (B), number of returns into closed arms (C) the types of dendritic spines
and time spent in the center of maze (D). Box diagrams show interquartile range, horizontal lines are
median and whiskers represent 5th and 95th percentiles. Outliers are data outside 5th to 95th revealed that in the sensory-
percentile (n = 21–25 per sex in each group). *p < 0.05, **p < 0.01 compared to control female rats. deprived male rats, the thin
SD: sensory-deprived. dendritic spines were the most
reduced type, especially on the
basal dendrites of CA1 pyramidal
neurons. In female rats,
mushroom and thin spines were
A Control B most affected in apical and basal
4 SD 400 ### dendrites of CA1 pyramidal
Trials in acquisition session
Step through latency (s)
neurons and apical dendrites of

* CA3 pyramidal neurons, while on
3 300 the basal dendrite of CA3
pyramidal neurons, only thin spine
were prominently reduced (Fig. 10).
2 200 The soma size of CA1 and CA3
neurons did not show a significant
difference between controls and
1 100 sensory deprived young adult rats
(data not presented). We did not
detect a significant difference in the
0 0 density of pyramidal neurons in the
Control SD Male Female CA1 and CA3 subfields of the
hippocampus between male and
Fig. 4. Effects of postnatal sensory deprivation of barrel cortex on passive avoidance performance. female rats in the control group.
Sensory deprivation did not affect the number of trials to acquisition during training (data were pooled Long-term postnatal whisker
for both sexes of control, n = 43, and SD animals, n = 46) (A), but sex-dependently reduced step deprivation significantly reduced
through latency of female rats in the retention test performed 24 h after the training (n = 21–24 per
sex in each group) (B). Box diagrams show interquartile range, horizontal lines are median and neuronal density in CA1 and CA3
whiskers represent 5th and 95th percentiles. Outliers are data outside 5th to 95th percentile. regions of both male and female
*p < 0.05 compared to control female rats. ###p < 0.001 compared to SD male rats. rats (Fig. 11).
A C
Male Control
6 Control 6 Male
Reference memory errors

5 SD 5 Female
4 4 *
* *
3 3
*
2 2
1 1
0 0
0 1 2 3 4 5 6 7 8 9 10 11 12 0 1 2 3 4 5 6 7 8 9 10 11 12
B D
Female SD
6 6 Male

Control
5 SD 5 Female
4 4
3 3
2 2
1 1
0 0
0 1 2 3 4 5 6 7 8 9 10 11 12 0 1 2 3 4 5 6 7 8 9 10 11 12
Days of testing Days of testing
Fig. 5. Effects of sensory deprivation on the spatial reference memory performance in the radial arm maze. Sensory deprivation increased
reference memory errors in male rats (A), but not in female rats (B). The normal difference that was observed between male and female rats in the
control group (C) was eliminated in the sensory-deprived (SD) rats (D). n = 17–23 per sex in each group. The data are presented as mean ± SEM.
Mean differences of all groups were analyzed using Kruskal-Wallis followed by Dunn’s multiple comparison post hoc test, but the results are
presented as pairwise comparisons in the line graphs. *p < 0.05.
DISCUSSION area of the open field is usually considered as an index

of reduced anxiety and increased exploratory/risk-taking
We found that chronic postnatal whisker deprivation behavior (Shieh and Yang, 2019). Given that even blind
affects behavioral responses of young adult rats, mainly rats with intact whiskers are capable of scoring well in a
in a sex dependent manner. The major finding of the gap-crossing test (Kleinfeld, 2008), it is apparent that
current study was that these enduring behavioral whiskers have a crucial role in generating a tactile map
alterations are associated with modifications of neuronal of the environment, perception of the surrounding and
morphology and density in the CA1 and CA3 navigational movements. There are papers reporting
hippocampal subfields, neural sites far away from the failed gap-crossing ability during adolescence after
deprived cerebral cortex, i.e. the barrel cortex, and neonatal whisker trimming (Lee et al., 2009; Chu et al.,
these modifications seem to contribute to the behavioral 2013), showing that whisker trimming during the critical
outcomes. neonatal period is enough to set the sensory apparatus
Long-term postnatal whisker deprivation did not alter out of order in the course of a tactile-specific challenge.
the number of line crossing and off-wall rearing, but We assume, a poor and imprecise representation of the
increased the time spent in the center area of the open surrounding tactile world shaped by the blunt receptive
field in both male and female rats. The number of line fields of neurons in the deprived cortex (Rema et al.,
crossing and rearing are mostly used as indices of 2003) has led to a pale perceptual image of the world,
horizontal and vertical motor activity, respectively, but ending up with excessive explorative behaviors for gath-
these are also indicators of exploratory activity ering enough information from the environment to make
(Zimcikova et al., 2017). The time spent in the central a proper behavioral response. Even partial sensory
A C
Male Control
3 Control 5 Male
Working memory errors

SD Female
4
2
3
* 2 ** ***
1
*
1
0 0
0 1 2 3 4 5 6 7 8 9 10 11 12 0 1 2 3 4 5 6 7 8 9 10 11 12
B Female D SD
5 5
Control Male
4
SD Working memory errors 4
Female
** *
3 * ** *
3
***
*** *
2 2 *
*
1 1
0 0
0 1 2 3 4 5 6 7 8 9 10 11 12 0 1 2 3 4 5 6 7 8 9 10 11 12
Days of testing Days of testing
Fig. 6. Effects of sensory deprivation on the spatial working memory performance in the radial arm maze. Sensory deprivation increased working
memory errors in both male (A) and female rats (B). The normal difference that was observed between male and female rats in the control group (C)
was even more intensified in the sensory-deprived (SD) rats (D). n = 17–23 per sex in each group. The data are presented as mean ± SEM. Mean
differences of all groups were analyzed using Kruskal-Wallis followed by Dunn’s multiple comparison post hoc test, but the results are presented as
pairwise comparisons in the line graphs. *p < 0.05, **p < 0.01 and ***p < 0.001.
deprivation of barrel cortex during the first postnatal week female mice for their experiments and performed the
impairs whisker-dependent exploratory behavior in mice, gap-crossing test on immature animals (PND31-33), but
which necessitates more exploratory activity in gap- reported no sex difference. In our study, however, the
crossing task, evidenced by more approaches to the increased activity against the walls was only significant
gap (Papaioannou et al., 2013). Our assumption can also in female rats (Papaioannou et al., 2013). Haridas et al.,
be verified by pondering on the explorative behaviors (2018) also reported that acute whisker desensitization
observed in our open field test, where SD rats try signifi- of adult male mice by lidocaine increases the time spent
cantly more on-wall rearing attempts but perform alike in the center of the open-field arena (Haridas et al.,
control rats while doing off-wall rearing. In contrast to 2018). Although it is difficult to compare our study with
off-wall rearing which is mainly associated with visual the aforementioned works, due to the differences in the
experience, on-wall rearing is performed against a sur- paradigm and method of sensory deprivation plus the nat-
face, and also involves active whisker-mediated explo- ural differences in behaviors of rats and mice, but they
ration. The observed increase of on-wall rearing in also interpreted this anxiolytic effect as a consequence
sensory-deprived rats could be attributed to the blunt vib- of sensory insufficiency. Meanwhile, these findings can-
rissal tactile perception of the surrounding surfaces. The not discount the possible involvement of indirect effects
impaired tactile acuity may also contribute to the aug- on areas with motor functions. The development of motor
mented visits to the central area of the open field, which cortex and the functional properties of its neurons are
can also be associated with whisker-dependent explo- highly dependent on early-life tactile experiences
ration of the surface. This should be mentioned that (Donoghue and Sanes, 1988). It has been shown that
Papaioannou et al. (2013) who had used both male and neonatal whisker deprivation reduces the size of M1 vib-
Male Female anxiety evidenced by increased

8 10 time in the exposed arms of the
Reference memory erros

Reference memory erros
†
elevated plus maze or central area
##
of the open-field box might be an
* 8 ††
6 indicative of increased risk-taking
† * and aggressive behaviors
6 (Valvassori et al., 2017) as
#
4 reported in other sensory depriva-
4 tion studies directly measured
aggressive behaviors (Soumiya
2 et al., 2016). Whisker trimming
2
has been reported to cause distur-
bances in the regulation of
0 0 amygdala-dependent functions
saline Sc 0.1 Sc 0.2 saline Sc 0.1 Sc 0.2 (Soumiya et al., 2016). Presum-
ably, an imbalance among net-
10 Control 15 works directly or indirectly
SD †† connecting barrel field in the pri-

8 ### mary somatosensory cortex
† (S1BF) and amygdala caused by
10 sensory deprivation is implicated
6 † in the aggressive or risk-taking
# behaviors registered in the ele-
4 vated plus maze and open-field
5 tests.
2 Meanwhile the data pertaining
fear-based memory in the current
0 study confirms such assumption
0 to some extent. We found that
saline Sc 0.1 Sc 0.2 saline Sc 0.1 Sc 0.2
long-term postnatal whisker
Fig. 7. The effects of two doses of scopolamine (SC), 0.1 mg/kg and 0.2 mg/kg, on the spatial deprivation also influenced the
reference and working memory of control and sensory-deprived (SD) rats in the radial arm maze. The fear-based memory of the rats.
lower dose of scopolamine induced more impairment of reference memory in SD rats than control Passive avoidance retention was
animals, while its higher concentration was less effective in SD female rats. The effect of scopolamine impaired in SD female rats, while
on working memory was not significantly different between control and SD rats. Box diagrams show
interquartile range, horizontal lines are median and whiskers represent 5th and 95th percentiles. it was not significantly affected in
Outliers are data outside 5th to 95th percentile. n = 17–23 per sex in each group. *p < 0.05 SD male rats. Amygdala not only
compared to drug-matched control rats, #p < 0.05, ##p < 0.05 and ###p < 0.001 compared to assesses fear and anxiety
saline-injected control rats, yp < 0.05 and yyp < 0.05 compared to saline-injected SD rats. attributed to stimuli but also
evaluates rewarding or aversive
consequences of a behavior,
rissa representation and alters its output, which affects
thereby strongly affecting sensory perceptions, memory
the highly integrated sensory–motor behaviors including
qualities and behavioral strategies (White and
exploratory activity (Milani et al., 1989; Huntley, 1997).
McDonald, 1993; Maren and Holmes, 2016). Several
Accordingly, the structural and functional refinements of
brain regions contribute to fear memory that include, but
motor cortices may also take part to the altered motor
are not limited to amygdala and hippocampus (Pittenger
and exploratory activity of SD rats, though the extent that
et al., 2006) that are reciprocally connected and are coor-
such possible alterations contribute to the SD-induced
dinately activated during fear learning and memory retrie-
behavioral outcomes requires further studies.
val (Pitkänen et al., 2000). Hippocampal outputs to the
The lower level of anxiety of SD rats, evidenced in
basolateral amygdala provide contextual information that
augmented visits to the central area of the open-field
are essential for fear conditioning (Maren and Fanselow,
box, was further supported by reduced defecation and
1995; Fendt and Fanselow, 1999). The activity of both
shortened time of self-grooming, particularly in female
CA1 and CA3 pyramidal neurons has been implicated in
SD rats. The behavioral performance in the open-field
the retrieval of fear memories (Hall et al., 2001; Sun
test was accordingly correlated with the observations in
et al., 2017). The retrieval of contextual memory is corre-
the elevated plus-maze; where once again, female SD
lated with selective activation of CA1 hippocampal neu-
rats spent more time in the exposed arms of the maze.
rons (Hall et al., 2001). The reactivity of CA3 neurons
Even though it is hard to interpret based on these two
during retrieval of fear memory has also been reported
tests whether the higher number of open-arm entries/
(Sun et al., 2017).
closed-arm returns as well as the increased time spent
Spatial memory performance in the radial arm maze, a
in the junction of the arms is the fated outcome of
classical hippocampus-dependent test, was also impaired
higher explorative behavior or a token of hesitant
by chronic postnatal whisker deprivation in a sex-
decision-making (Sestakova et al., 2013). The reduced
A Control SD C
Apical dendrites - Male Apical dendrites - Control
10
Number of intersections
10
8 Control 8 Male
SD Female
6 6
Male
4 4
2 2
0 0
0 100 200 300 400 0 100 200 300 400
Apical dendrites - Female Apical dendrites - SD
8 8
Control Male
Female
6 SD 6 Female
4 4
2 2
0 0
0 100 200 300 400 0 100 200 300 400
Radial distance from soma (µm) Radial distance from soma (µm)
B
Total dendritic length (103 µm)
Apical dendrites Basal dendrites

D Basal dendrites - Male Basal dendrites - Control
4 #
4
#
# ***
15 Control 15 Male
2 2 * SD Female
10 10
0 0
Male Female Male Female
5 5
Number of branch points
40
40
* 0 0
* 0 50 100 150 200 250 0 50 100 150 200 250
20 *
20 Basal dendrites - Female rats Basal dendrites - SD
15
0 0 12
Male Female Male Female Control Male
Number of terminal points
10 SD Female
Control 8
SD
40 40
* **
5 4
20 20 *
0 0
0 50 100 150 200 250 0 50 100 150 200 250
0 0 Radial distance from soma (µm) Radial distance from soma (µm)
Fig. 8. The effects of sensory deprivation on the dendritic morphology of CA1 pyramidal neurons in male and female rats. A: Representative
photomicrographs of Golgi-stained hippocampal CA1 pyramidal neurons from control and sensory-deprived male and female rats. Scale
bar = 100 mm. B: The effects of whisker deprivation on total dendritic length, branch points and terminal points in apical and basal dendrites of CA1
neurons. Box diagrams show interquartile range, horizontal lines are median and whiskers represent 5th and 95th percentiles. Outliers are data
outside 5th to 95th percentile. Sholl plots (depicted as mean ± SEM) show the number of apical (C) and basal (D) dendritic intersections at
concentric rings with increasing radii centered on the soma of CA1 neurons. The left panel represents differences between control and SD rats in
either male or female rats, the right panel shows sex differences in dendritic intersections within each group. *p < 0.05, **p < 0.01, ***p < 0.001
compared to sex-matched control, #p < 0.05, ##p < 0.01 compared to male rats in the same group.
dependent manner. Here, we reported that male SD rats memory errors in both male and female rats but this effect
had more reference memory errors compared to the sex- was more pronounced in females. Earlier studies have
matched controls. Sensory deprivation increased working reported the effects of sensory deprivation on the
A Control SD C
Apical dendrites - Male Apical dendrites - Control
10
8 Control Male
8
SD Female
6
6
Male
4 4
2 2
0 0
0 100 200 300 400 0 100 200 300 400
Apical dendrites - Female Apical dendrites - SD
10
8 Control 8 Male
Female
SD Female
6 6
4 4
2 2
0 0
0 100 200 300 400 0 100 200 300 400
Radial distance from soma (µm) Radial distance from soma (µm)
B Apical dendrites Basal dendrites
Number of branch points Total dendritic length (103 µm)
4 D
Basal dendrites - Male Basal dendrites - Control
4
#
2 12 12 Male
Control
2
SD Female
8 8
0 0
4 4
30 40 Control
# SD
0 0
20
0 50 100 150 200 250 0 50 100 150 200 250
#
20
10
*** Basal dendrites - Female rats Basal dendrites - SD
15
12
0 0 Control
Male
SD Female
Number of terminal points
10
30 8
40
20 5 4
*** $$
20
10
0 0
0 50 100 150 200 250 0 50 100 150 200 250
0 0 Radial distance from soma (µm) Radial distance from soma (µm)
Fig. 9. The effects of sensory deprivation on the dendritic morphology of CA3 pyramidal neurons in male and female rats. A: Representative photo
micrographs of Golgi-stained hippocampal CA3 pyramidal neurons from control and sensory-deprived male and female rats. Scale bar = 100 mm.
B: The effects of whisker deprivation on total dendritic length, branch points and terminal points in apical and basal dendrites of CA3 neurons.
Box diagrams show interquartile range, horizontal lines are median and whiskers represent 5th and 95th percentiles. Outliers are data outside 5th to
95th percentile. Sholl plots (depicted as mean ± SEM). Sholl plots representing the number of apical (C) and basal (D) dendritic intersections at
concentric rings with increasing radii centered on the soma of CA3 neurons. The left panel show differences between control and sensory-deprived
(SD) rats in either male or female rats, the right panel represents sex differences in dendritic intersections within each group. *p < 0.05, **p < 0.01,
***p < 0.001 compared to sex-matched control, #p < 0.05, ##p < 0.01, ###p < 0.001 compared to male rats in the same group.
learning and memory. It has been shown that whisker- (Haridas et al., 2018). Soumiya et al., (2016) reported that
related tactile information are essential for the short whisker trimming of male mice during early postnatal per-
term recognition memory in novel object recognition test iod (PND1–PND10) impairs tactile sensory performance
A CA1 apical dendrite B CA1 basal dendrite

Control
SD
30 Male Female 40
Male Female Control
SD
Spines /20 µm
Spines /20 µm
30
*
20 *
20
10
* * 10 *
*
0 0
m
m
m
m
in
in
by
by
by
l
by
in
l
in
ta
ta
ta
ta
oo
oo
oo
Th
oo
Th
Th
Th
ub
ub
ub
To
To
ub
To
To
hr
hr
hr
hr
St
St
St
St
us
us
us
us
M
M
M
C CA3 apical dendrite D CA3 basal dendrite

Control
SD
30 Male Female Male Female Control

SD
Spines /20 µm
Spines /20 µm
** 20 ***
20 *
10
10
** ** ***
0 0
m
m
in
m
by
in
by
l
l
by
in
by
l
l
in
ta
ta
ta
ta
oo
oo
oo
Th
oo
Th
Th
Th
ub
ub
To
To
ub
ub
To
To
hr
hr
hr
hr
St
St
St
St
us
us
us
us
M
M
M
M
Fig. 10. Sensory deprivation altered the density of spines on dendrites of CA1 and CA3 pyramidal neurons. Representative photomicrographs of
apical and basal dendritic segments of CA1 and CA3 neurons from control and sensory-deprived (SD) male and female rats are shown at the top of
(A–D) panels. Scale bar = 10 mm. Density of different spine types in control and sensory-deprived male and female rats are represented at the
bottom of (A–D) panels. Box diagrams show interquartile range, horizontal lines are median and whiskers represent 5th and 95th percentiles.
*p < 0.05, **p < 0.01 and ***p < 0.001 compared to control.
in gap-crossing test, 8–9 weeks after birth, while learning the hippocampal function (Morris, 1981). Zhao and col-
and memory in a whisker-cued eight-arm radial maze is leagues have reported that temporary auditory depriva-
not affected (Soumiya et al., 2016). In this type of radial tion by perforating the eardrum of male rats on PND 14
maze, what is tested is the tactile perception-based impairs spatial memory performance in Morris water
reward-driven memory, rather than visual-cued spatial maze and Y maze performed on PND 42, when the ear-
memory and animal have to memorize the relationship drum has been healed. Structural and functional studies
between a whisker cue at the entrance of the bated arms on hippocampal slices revealed decreased number of
and the food reward at the ends. This essential difference dendritic spines on CA1 neurons, reduced postsynaptic
of the maze task and the shorter period of whisker depri- densities and suppressed NMDA receptor-mediated post-
vation may underlie the different findings, compared to synaptic currents (Zhao et al., 2018). It is reasonable to
our study. The spatial memory task in a common radial interpret that the impairment of spatial memory in SD rats
maze, as the one we employed, is highly dependent on found in this study, stems from evident alteration on neu-
A CA1 region CA3 region

Control SD Control SD
Male
Female
CA1 region CA3 region

Number of neurons/0.063mm2
Number of neurons/0.063mm2
B 100 100
Control
SD
** **
50 *** 50 **
0 0
Fig. 11. Effects of whisker deprivation on the numbers of pyramidal neurons in CA1 and CA3 subfields of the hippocampus in males and females. A:
Representative images of Cresyl Violet stained neurons in CA1 and CA3 regions. B: Comparison of neuronal density in CA1 and CA3 regions
showed a significant reduction of density in both male and female sensory-deprived (SD) rats compared to control rats. n = 4–6 per sex in each
group. **p < 0.01 and ***p < 0.001 compared to control.
ronal morphology and density in the hippocampus, even sufficient training reduces the level of reference memory
though the structural and functional alteration in other errors, the effect of scopolamine on this type of memory
brain circuits contributing to the task could also potentially becomes evident (Lydon and Nakajima, 1992). Interest-
be implicated. ingly, here we found that the lower dose of scopolamine
The septohippocampal cholinergic input innervates was not able to induce significant working memory errors
CA1 and CA3 pyramidal neurons in their basal in female control rats. In support of Lydon and Nakajima’s
dendrites. This cholinergic projection is involved in assumption, the higher baseline level of working memory
learning/memory and attention (Teles-Grilo Ruivo and errors in control female rats, compared to males, might
Mellor, 2013). In the current study the lower dose have masked the potential amnestic effect of the lower
(0.1 mg/kg) of scopolamine impaired working memory in dose of scopolamine on working memory in female rats.
control and SD male rats, while the reference memory The finding that the lower dose of scopolamine impaired
was impaired by a lower dose of scopolamine only in reference memory in both male and female SD rats (while
SD rats. Many studies have reported that scopolamine it was not able to do so in control rats) could be a result of
mainly disrupts spatial working memory but spares spatial partial impairment of septal cholinergic inputs to the hip-
reference memory (Hodges Jr et al., 2009; Kay et al., pocampus, which make this system more vulnerable to
2010). Here, the higher dose of scopolamine impaired ref- even a slight disruption by a low dose of scopolamine.
erence memory in both control and SD male and female Meanwhile, the higher dose of scopolamine impaired ref-
rats. The distinctive action of scopolamine on the spatial erence memory in male and female controls, but this
working and reference memory (usually studied in male effect was much weaker in the SD rats. This finding also
animals) has been attributed to the level of training; when supports the lower contribution of cholinergic system to
the spatial memory, as a consequence of its impairment. basal dendrites were reduced. The reduction of dendritic
The septohippocampal cholinergic innervation regulates spines reached the significance level only for the total
neuronal activity and synaptic plasticity of hippocampal density of spines of all types (not for any of the three
pyramidal neurons (Dannenberg et al., 2017; Maurer types), and was not affected on the basal dendrites of
and Williams, 2017) and a potential impairment of the CA3 neuros of SD male rats. In SD female rats, apical
cholinergic system, besides the contribution to memory dendrites of CA3 neurons were not affected but the
impairment, may also be involved in the structural basal dendrites showed more arborization while the
changes of the pyramidal neurons. This assumption density of dendritic spines was reduced in both apical
requires further work to be verified. and basal dendrites of SD female rats. The effects of
The observed structural remodeling of neuronal postnatal whisker deprivation on behavioral outcomes
dendrites and density of dendritic spines in the were sex-dependent, as in the case of memory tests.
hippocampal CA1 and CA3 subregions reflects the This might be mediated by sex-dependent effects of
alterations in their connectivity with multiple input whisker deprivation on the complexity of apical dendrites
sources that in turn could affect their processing of CA1 neurons and both apical and basal dendrites of
capacity and functional outputs. Experience-dependent CA3 neurons. We also found that thin spines were
neuronal activity is required to establish and selectively reduced in basal and apical dendrites of CA1 neurons of
preserve synaptic connectivity; a key process for normal female SD rats. The reduction of mushroom spines was
wiring of neural circuits (De Roo et al., 2008; Johnson- also significant for these regions unless for basal
Venkatesh et al., 2015). Neurons in the barrel cortex dendrite of CA3 neurons in female SD rats. In male SD
show several structural adaptations to the reduced/elimi- rats, only the thin spines showed significant reduction in
nated sensory inputs started during early postnatal days. the basal dendrite of CA1 neurons. The thin spines are
Increased secondary branch points (Maravall et al., dominated by NMDA receptors and have high structural
2004), reduced dendritic spine loss (Zuo et al., 2005), flexibility, enabling them to expand and stabilize or
impaired development and reduced density of dendritic retract. Mushroom spines are more mature and stable
spine (though no longer detectable in adult animals) spines dominated by AMPA receptors. These features
(Briner et al., 2010), enlarged soma size, increased den- have suggested the thin spines as mediators of learning
dritic protrusion and expansion of basilar dendritic arbor that could be turned into the mushroom spines, as
and retraction of apical dendrites (Chen et al., 2012; memory spines (Bourne and Harris, 2007). The more pro-
Chen et al., 2015) are among the morphological alter- nounced and significant reduction of the thin and mush-
ations reported in pyramidal neurons following sensory room spines density in CA1 and CA3 pyramidal neurons
deprivation of barrel cortex. In the current study we used of SD female rats could contribute to the more severe
a very long-term tactile deprivation paradigm that was memory impairment, and possibly other behavioral alter-
almost unique in terms of the onset and duration besides ations observed in females following whisker deprivation.
the brain structure that was studied, a region far higher in The well-known mutual connections of the hippocampus
the hierarchy of processing and integrating sensory infor- with cerebral cortex and amygdala (Pikkarainen et al.,
mation. The activity of hippocampal pyramidal neurons is 1999; Pitkänen et al., 2000), the contribution of hippocam-
evidently influenced by sensory experiences through tem- pus to anxiety, spatial memory and fear based memory
poroammonic path. Sensory inputs drive the activity of (Best and Orr Jr, 1973; Bernabeu et al., 1997; Izquierdo
CA1 and CA3 neurons through direct and indirect tem- et al., 2008), together with our findings on the sex-
poroammonic connections that are important for proper dependent alterations of neuronal morphology in the
structural and functional development of hippocampal CA1 and CA3 hippocampal subregions of SD rats may
neurons (Hill and Best, 1981; Johnson-Venkatesh et al., provide further explanations for the results obtained in
2015; Milshtein-Parush et al., 2017). In behaving rats, the behavioral test. It should be noted that the differences
touch-guided behavior or electrical stimulation of the of neuronal structure between sexes do not always
infraorbital nerve, which carries sensory signals from ‘‘cause” differences in cognitive functions and behavior,
whiskers to the brain, evokes firing of CA1 neurons but may also ‘‘compensate” for differentiating effects that
(Pereira et al., 2007; Itskov et al., 2011; Vatanparast potentially could originate from other sources (De Vries,
et al., 2013). It has been shown that whisker deprivation 2004).
during early life reduces the activity of CA3 pyramidal Multiple mechanisms may contribute to the selective
neurons in mice and facilitates their synapses to CA1 neu- retraction/expansion of dendritic arbor and dendritic
rons (Milshtein-Parush et al., 2017). spine loss in SD rats. An important candidate could be
In this work, some structural alterations in the the heterogeneous source of synaptic inputs, depending
morphology and density of CA1 and CA3 neurons were on the type of neuron (CA1 or CA3 pyramidal neurons)
detected that, similar to the behavioral outcomes, as well as on the location of dendritic tree in a specific
showed sex-dependency. Whisker deprivation reduced neuronal type. The basal dendrites and proximal region
arborization and density of dendritic spines on the apical of apical dendrites of CA1 neurons mainly receive inputs
dendrites of CA1 neurons of female rats, while the basal from the Schaeffer collaterals of CA3 pyramidal neurons
dendrites of CA1 neurons showed retraction along with while the distal segments of apical dendrites receive
reduced density of dendritic spines in both male and direct innervation from the entorhinal cortex via the
female rats. CA3 pyramidal neurons showed extended performant pathway. The apical dendrites of CA3
arborization of apical dendrites in SD male rats but their neurons are innervated by the axons of granule cells
(mossy fibers) and the basal dendrites primarily receive processing hierarchy. The witnessed discrepancies in
recurrent inputs from other CA3 neurons (Spruston, the behavioral alterations and neuronal modifications of
2008). In accord with behavioral findings, the structural male and female SD rats, could arise from differential
alterations of pyramidal neurons were more pronounced interaction of sensory deprivation with internal
in female rats. The expansion of basal dendritic arbors substrates that underlie intrinsic sex differences
of CA3 neurons, which can indicate increased local recur- between male and female rats. A further progress in
rent inputs, could be explained as an adaptive response discovering the true mechanisms behind our
to compensate for the reduced indirect temporoammonic observations, require studying the molecular mediators
inputs. On the other hand, a ‘‘loss-of-function” associated governing the functional organization and architecture of
with reduced direct inputs from entorhinal cortex to CA1 neural circuits in an activity-dependent medium.
apical dendrites, might underlie the retraction of CA1 api-
cal dendrites in female SD rats. A major challenge to
DECLARATIONS OF INTEREST
these hypotheses is the lack of such effects in the male
SD rats. Several studies have reported sex differences None.
in structure and plasticity of hippocampal neurons that
underlie the basal sex-related disparities in behavioral
ACKNOWLEDGMENTS
and cognitive functions and different responses to envi-
ronmental factors (Shors et al., 2001; Scharfman and This work was supported by a grant (No. 96005769) from
MacLusky, 2017; Yagi and Galea, 2019; Brandt et al., Iran National Science Foundation (INSF) and Cognitive
2020). Such sex-based disparities of hippocampal Science and Technology Council (CSTC). We thank
responsiveness may have provided a ground for the dif- Mojgan Jouybar, Fatemeh Taghavi, Nima Rahaei and
ferent effects of SD on the neuronal morphology in CA1 Zahra Naderi for technical assistance, observing video
and CA3 hippocampal subregions of male and female tracks and extracting behavioral data.
rats, and the consequent outcomes in the vast
hippocampal-dependent behavioral paradigms. REFERENCES
At present, an important open question is the
molecular mediators that correlate the absence of Alipour V, Hoseinpour F, Vatanparast J (2019) Persistent alterations
sensory inputs to the altered morphology/density of in seizure susceptibility, drug responsiveness and comorbidities
hippocampal pyramidal neurons, and cognitive and associated with chemical kindling after neonatal exposure to an
behavioral outcomes. Altered expression of organophosphate. Neurotoxicology 73:92–99.
Bencsik N, Pusztai S, Borbély S, Fekete A, Dülk M, Kis V, Pesti S,
neurotrophins, especially brain-derived neurotrophic
Vas V, Szu }cs A, Buday L, Schlett K (2019) Dendritic spine
factor, is among the leading candidates. Different morphology and memory formation depend on postsynaptic
neurotrophins are expressed in the hippocampus, that Caskin proteins. Sci Rep 9(1). https://doi.org/10.1038/s41598-
are important for neuronal survival, maintenance of 019-53317-9.
dendritic spines and regulation of dendritic arborization Bernabeu R, Bevilaqua L, Ardenghi P, Bromberg E, Schmitz P,
that usually work selectively and in an activity- Bianchin M, Izquierdo I, Medina JH (1997) Involvement of
dependent manner (McAllister, 2000; Kellner et al., hippocampal cAMP/cAMP-dependent protein kinase signaling
pathways in a late memory consolidation phase of aversively
2014). In the cerebral cortex, sensory experience controls motivated learning in rats. Proc Natl Acad Sci 94(13):7041–7046.
the neuronal development and function through an Best PJ, Orr Jr J (1973) Effects of hippocampal lesions on passive
activity-driven expression of neurotrophins (Rocamora avoidance and taste aversion conditioning. Physol Behav 10
et al., 1996; Jiao et al., 2011). The altered excitability of (2):193–196.
hippocampal CA1 and CA3 pyramidal neurons is another Bourne J, Harris KM (2007) Do thin spines learn to be mushroom
critical factor that might be correlated to the structural spines that remember? Curr Opin Neurobiol 17(3):381–386.
Brandt N, Löffler T, Fester L, Rune GM (2020) Sex-specific features
changes and be involved in the cognitive and behavioral
of spine densities in the hippocampus. Sci Rep 10:1–12.
impairments as well. Further work to clarify this issue, Breton JD, Stuart GJ (2009) Loss of sensory input increases the
and also structural analysis of CA1 and CA3 neurons dur- intrinsic excitability of layer 5 pyramidal neurons in rat barrel
ing an earlier (PND 40) and later periods of development cortex. J Physiol 587:5107–5119.
(PND 100) are warranted. Briner A, De Roo M, Dayer A, Muller D, Kiss JZ, Vutskits L (2010)
In summary, here we reported that long-term sensory Bilateral whisker trimming during early postnatal life impairs
dendritic spine development in the mouse somatosensory barrel
deprivation of the barrel-cortex, as an axial sensory
cortex. J Comp Neurol 518(10):1711–1723.
processing unit in rodents, concludes in a severe Chen C-C, Bajnath A, Brumberg JC (2015) The impact of
alteration in the structure of hippocampal CA1 and CA3 development and sensory deprivation on dendritic protrusions in
regions and hippocampal-dependent behaviors. Our the mouse barrel cortex. Cereb Cortex 25: 1638–1653.
observations provide another line of evidence for the Chen C-C, Tam D, Brumberg JC (2012) Sensory deprivation
idea that the behavioral impairments following to differentially impacts the dendritic development of pyramidal
versus non-pyramidal neurons in layer 6 of mouse barrel cortex.
sensory deprivation are not solely underlain by
Brain Struct funct 217(2):435–446.
neuroplastic changes taking place in the sensory Chu Y-F, Yen C-T, Lee L-J (2013) Neonatal whisker clipping alters
cortices. Instead, the activity-dependent neural behavior, neuronal structure and neural activity in adult rats.
alterations could be tracked in the regions having tight Behav Brain Res 238:124–133.
structural and functional associativity with cerebral Dannenberg H, Young K, Hasselmo M (2017) Modulation of
cortex at a higher level of the sensory information hippocampal circuits by muscarinic and nicotinic receptors.
Front Neural Circuits 11:102.
Das G, Reuhl K, Zhou R, 2013. The golgi–cox method, In: Neural Kutzing MK, Langhammer CG, Luo V, Lakdawala H, Firestein BLJJ
Development. Springer, pp. 313-321. (2010) Automated Sholl analysis of digitized neuronal morphology
De Roo M, Klauser P, Garcia PM, Poglia L, Muller D (2008) Spine at multiple scales. J Vis Exp 45 e2354.
dynamics and synapse remodeling during LTP and memory Langhammer CG, Previtera ML, Sweet ES, Sran SS, Chen M,
processes. Prog Brain Res 169:199–207. Firestein BL (2010) Automated Sholl analysis of digitized neuronal
De Vries GJ (2004) Minireview: sex differences in adult and morphology at multiple scales: whole cell Sholl analysis versus
developing brains: compensation, compensation, compensation. Sholl analysis of arbor subregions. Cytometry A 77A
Endocrinology 45:1063–1068. (12):1160–1168.
Donoghue JP, Sanes JN (1988) Organization of adult motor cortex Lee LJ, Chen WJ, Chuang YW, Wang YC (2009) Neonatal whisker
representation patterns following neonatal forelimb nerve injury in trimming causes long-lasting changes in structure and function of
rats. J Neurosci 8(9):3221–3232. the somatosensory system. Exp Neurol 219(2):524–532.
Eggermann E, Kremer Y, Crochet S, Petersen CH (2014) Cholinergic Liu Yz, Wang Y, Tang W, Zhu Jy, Wang Z (2018) NMDA receptor-
signals in mouse barrel cortex during active whisker sensing. Cell gated visual responses in hippocampal CA1 neurons. J Physiol
Rep 9(5):1654–1660. 596(10):1965–1979.
Eichenbaum H, Cohen N (2014) Can we reconcile the declarative Lydon RG, Nakajima S (1992) Differential effects of scopolamine on
memory and spatial navigation views on hippocampal function? working and reference memory depend upon level of training.
Neuron 83(4):764–770. Pharmacol Biochem Be 43(2):645–650.
Faherty CJ, Kerley D, Smeyne RJ (2003) A Golgi-Cox morphological Maravall M, Koh IY, Lindquist WB, Svoboda K (2004) Experience-
analysis of neuronal changes induced by environmental dependent changes in basal dendritic branching of layer 2/3
enrichment. Dev Brain Res 141(1-2):55–61. pyramidal neurons during a critical period for developmental
Fendt M, Fanselow MS (1999) The neuroanatomical and plasticity in rat barrel cortex. Cereb Cortex 14:655–664.
neurochemical basis of conditioned fear. Neurosci Biobehav Maren S, Fanselow MS (1995) Synaptic plasticity in the basolateral
Rev 23(5):743–760. amygdala induced by hippocampal formation stimulation in vivo. J
Graves A, Moore S, Bloss E, Mensh B, Kath W, Spruston N (2012) Neurosci 15(11):7548–7564.
Hippocampal pyramidal neurons comprise two distinct cell types Maren S, Holmes A (2016) Stress and fear extinction.
that are countermodulated by metabotropic receptors. Cell Rep Neuropsychopharmacol 41(1):58–79.
76(4):776–789. Maurer SV, Williams CLJF (2017) The cholinergic system modulates
Hall J, Thomas KL, Everitt BJ (2001) Fear memory retrieval induces memory and hippocampal plasticity via its interactions with non-
CREB phosphorylation and Fos expression within the amygdala. neuronal cells. Front Immunol 8:1489.
Eur J Neurosci 13(7):1453–1458. McAllister AK (2000) Cellular and molecular mechanisms of dendrite
Haridas S, Ganapathi R, Kumar M, Manda K (2018) Whisker growth. Cereb Cortex 10:963–973.
dependent responsiveness of C57BL/6J mice to different Merabet LB, Pascual-Leone A (2010) Neural reorganization following
behavioral test paradigms. Behav Brain Res 336:51–58. sensory loss: the opportunity of change. Nat Rev Neuroscience
Hill AJ, Best PJ (1981) Effects of deafness and blindness on the 11(1):44–52.
spatial correlates of hippocampal unit activity in the rat. Exp Milani H, Steiner H, Huston JPJB (1989) Analysis of recovery from
Neurol 74:204–217. behavioral asymmetries induced by unilateral removal of vibrissae
Hodges Jr DB, Lindner MD, Hogan JB, Jones KM, Markus EJ (2009) in the rat. Behav Neurosci 103(5):1067–1074.
Scopolamine induced deficits in a battery of rat cognitive tests: Milshtein-Parush H, Frere S, Regev L, Lahav C, Benbenishty A, Ben-
comparisons of sensitivity and specificity. Behav Pharmacol Eliyahu S, Goshen I, Slutsky I (2017) Sensory deprivation triggers
20:237–251. synaptic and intrinsic plasticity in the hippocampus. Cerebr Cortex
Huntley GW (1997) Differential effects of abnormal tactile experience 27: 3457-3470.
on shaping representation patterns in developing and adult motor Morales-Medina JC, Juarez I, Venancio-Garcı́a E, Cabrera SN,
cortex. J Neurosci 17(23):9220–9232. Menard C, Yu W, Flores G, Mechawar N, Quirion R (2013)
Itskov PM, Vinnik E, Diamond ME, Arabzadeh E (2011) Hippocampal Impaired structural hippocampal plasticity is associated with
representation of touch-guided behavior in rats: persistent and emotional and memory deficits in the olfactory bulbectomized
independent traces of stimulus and reward location. Plos One 6 rat. Neuroscience 236:233–243.
(1):e16462. Morris RGM (1981) Spatial localization does not require the presence
Izquierdo I, Bevilaqua LM, Rossato JI, Da Silva WC, Bonini J, Medina of local cues. Learn Motiv 12(2):239–260.
JH, Cammarota M (2008) The molecular cascades of long-term O’Keefe J (1976) Place units in the hippocampus of the freely moving
potentiation underlie memory consolidation of one-trial avoidance rat. Exp Neurol 51(1):78–109.
in the CA1 region of the dorsal hippocampus, but not in the Papaioannou S, Brigham L, Krieger P (2013) Sensory deprivation
basolateral amygdala or the neocortex. Neurotox Res 14(2- during early development causes an increased exploratory
3):273–294. behavior in a whisker-dependent decision task. Brain Behav 3
Jiao Y, Zhang Z, Zhang C, Wang X, Sakata K, Lu B, Sun Q-Q (2011) (1):24–34.
A key mechanism underlying sensory experience-dependent Paxinos G, Watson C (2006) The rat brain in stereotaxic coordinates:
maturation of neocortical GABAergic circuits in vivo. Proc Natl hard. cover edition. Elsevier.
Acad Sci 108(29):12131–12136. Pereira A, Ribeiro S, Wiest M, Moore LC, Pantoja J, Lin SC, Nicolelis
Johnson-Venkatesh EM, Khan MN, Murphy GG, Sutton MA, MAL (2007) Processing of tactile information by the hippocampus.
Umemori H (2015) Excitability governs neural development in a Proc Natl Acad Sci 104(46):18286–18291.
hippocampal region-specific manner. Development Peters A, Kaiserman-Abramof IR (1970) The small pyramidal neuron
142:3879–3891. of the rat cerebral cortex. The perikaryon, dendrites and spines.
Kay C, Harper DN, Hunt M (2010) Differential effects of MDMA and Am J Anat 127(4):321–355.
scopolamine on working versus reference memory in the radial Pikkarainen M, Rönkkö S, Savander V, Insausti R, Pitkänen A (1999)
arm maze task. Neurobiol Learn Mem 93(2):151–156. Projections from the lateral, basal, and accessory basal nuclei of
Kellner Y, Gödecke N, Dierkes T, Thieme N, Zagrebelsky M, Korte the amygdala to the hippocampal formation in rat. J Comp Neurol
MK (2014) The BDNF effects on dendritic spines of mature 403: 229-260.
hippocampal neurons depend on neuronal activity. Front Synaptic Pitkänen A, Pikkarainen M, Nurminen N, Ylinen A (2000) Reciprocal
Neurosci 6:5. connections between the amygdala and the hippocampal
Kleinfeld D, 2008. Vibrissa movement, sensation and sensorimotor formation, perirhinal cortex, and postrhinal cortex in rat: a
control, In: The New Encyclopedia of Neuroscience. pp. 155-177. review. Ann N Y Acad Sc 911: 369–391.
Pittenger C, Fasano S, Mazzocchi-Jones D, Dunnett SB, Kandel ER, Spruston N (2008) Pyramidal neurons: dendritic structure and
Brambilla R (2006) Impaired bidirectional synaptic plasticity and synaptic integration. Nat Rev Neurosci 9(3):206–221.
procedural memory formation in striatum-specific cAMP response Sun Q, Sotayo A, Cazzulino AS, Snyder AM, Denny CA, Siegelbaum
element-binding protein-deficient mice. J Neurosci 26 SA (2017) Proximodistal heterogeneity of hippocampal CA3
(10):2808–2813. pyramidal neuron intrinsic properties, connectivity, and
Rampon C, Jiang CH, Dong H, Tang Y-P, Lockhart DJ, Schultz PG, reactivation during memory recall. Neuron 95(3):656–672.e3.
Tsien JZ, Hu Y (2000) Effects of environmental enrichment on Teles-Grilo Ruivo L, Mellor J (2013) Cholinergic modulation of
gene expression in the brain. Proc Natl Acad Sci 97 hippocampal network function. Front Synaptic Neurosci 5:2.
(23):12880–12884. Ueno H, Suemitsu S, Matsumoto Y, Okamoto M (2015) Sensory
Ranjan A, Behari J, Mallick BN (2014) Cytomorphometric changes in deprivation during early postnatal period alters the density of
hippocampal CA1 neurons exposed to simulated microgravity interneurons in the mouse prefrontal cortex. Neural plast 2015.
using rats as model. Front Neurol 5:77. Valvassori SS, Resende WR, Dal-Pont G, Sangaletti-Pereira H, Gava
Rauschecker JP (1995) Compensatory plasticity and sensory FF, Peterle BR, Carvalho AndréF, Varela RB, Dal-Pizzol F,
substitution in the cerebral cortex. Trends Neurosci 18(1):36–43. Quevedo J (2017) Lithium ameliorates sleep deprivation-induced
Rema V, Armstrong-James M, Ebner FF (2003) Experience- mania-like behavior, hypothalamic-pituitary-adrenal (HPA) axis
dependent plasticity is impaired in adult rat barrel cortex after alterations, oxidative stress and elevations of cytokine
whiskers are unused in early postnatal life. J Neurosci 23 concentrations in the brain and serum of mice. Bipolar disord 19
(1):358–366. (4):246–258.
Rocamora N, Welker E, Pascual M, Soriano E (1996) Upregulation of van Praag H, Kempermann G, Gage FH (2000) Neural
BDNF mRNA expression in the barrel cortex of adult mice after consequences of enviromental enrichment. Nat Rev Neurosci 1
sensory stimulation. J Neurosci 16(14):4411–4419. (3):191–198.
Scharfman HE, MacLusky NJ (2017) Sex differences in hippocampal Vatanparast J, Naseh M, Baniasadi M, Haghdoost-Yazdi H (2013)
area CA3 pyramidal cells. J Neurosci Res 95:563–575. Developmental exposure to chlorpyrifos and diazinon differentially
Schliebs R, Bigl V, Biesold D (1982) Development of muscarinic affect passive avoidance performance and nitric oxide synthase-
cholinergic receptor binding in the visual system of monocularly containing neurons in the basolateral complex of the amygdala.
deprived and dark reared rats. Neurochem Res 7(9):1181–1198. Brain Res 1494:17–27.
Sestakova N, Puzserova A, Kluknavsky M, Bernatova I (2013) White N, Mcdonald R (1993) Acquisition of a spatial conditioned place
Determination of motor activity and anxiety-related behaviour in preference is impaired by amygdala lesions and improved by
rodents: methodological aspects and role of nitric oxide. fornix lesions. Behav Brain Res 55(2):269–281.
Interdiscip Toxicol 6:126–135. Wiesel TN, Hubel DH (1963) Single-cell responses in striate cortex of
Shieh K-R, Yang S-C (2019) Exploratory and agile behaviors with kittens deprived of vision in one eye. J Neurophysiol 26
central dopaminergic activities in open field tests in Formosan (6):1003–1017.
wood mice (Apodemus semotus). J Exp Biol 222. Yagi S, Galea LAM (2019) Sex differences in hippocampal cognition
Shors TJ, Chua C, Falduto J (2001) Sex differences and opposite and neurogenesis. Neuropsychopharmacol 44(1):200–213.
effects of stress on dendritic spine density in the male versus Zhang J-B, Chen L, Lv Z-M, Niu X-Y, Shao C-C, Zhang C, Pruski M,
female hippocampus. J Neurosci 21(16):6292–6297. Huang Y, Qi C-C, Song N-N (2016) Oxytocin is implicated in
Soetanto A, Wilson RS, Talbot K, Un A, Schneider JA, Sobiesk M, social memory deficits induced by early sensory deprivation in
Kelly J, Leurgans S, Bennett DA, Arnold SE (2010) Association of mice. Mol Brain 9:1–13.
anxiety and depression with microtubule-associated protein 2– Zhao J, Zhou Y, Li Z, Wang W, Chang K-W (2018) Learning gender-
and synaptopodin-immunolabeled dendrite and spine densities in neutral word embeddings. arXiv preprint arXiv:1809.01496.
hippocampal CA3 of older humans. Arch Gen Psychiatry 67 Zimcikova E, Simko J, Karesova I, Kremlacek J, Malakova J (2017)
(5):448–457. Behavioral effects of antiepileptic drugs in rats: Are the effects on
Soumiya H, Godai A, Araiso H, Mori S, Furukawa S, Fukumitsu H, mood and behavior detectable in open-field test? Seizure
Homberg J (2016) Neonatal whisker trimming impairs fear/ 52:35–40.
anxiety-related emotional systems of the amygdala and social Zuo Y, Yang G, Kwon E, Gan W-B (2005) Long-term sensory
behaviors in adult mice. Plos One 11(6):e0158583. deprivation prevents dendritic spine loss in primary
somatosensory cortex. Nature 436(7048):261–265.
(Received 19 June 2021, Accepted 5 November 2021)

(Available online 14 November 2021)

Yarmohammadi-Samani Et Al

Uploaded by

Copyright:

Available Formats

Yarmohammadi-Samani Et Al

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Yarmohammadi-Samani Et Al

Uploaded by

Copyright:

Available Formats

NEUROSCIENCE

Long-lasting Postnatal Sensory Deprivation Alters Dendritic

INTRODUCTION tional deﬁcits. These alterations are not restricted to the

Radial arm maze Passive avoidance test

Golgi-cox staining (http://research.ssm.edu/cnic/tools-ns.html), and spines

male and female rats in the reference memory that

A D 100 Sholl intersections was detected

10 * (Fig. 8C). Signiﬁcant reduction of

** SD more Sholl intersections in the

4 intermediate segment of basal

30 CA3 neurons of male and female

A C intermediate ranges, while in

Closed arm returens

60 100 CA1 and CA3 pyramidal neurons

Step through latency (s)

neurons and apical dendrites of

Reference memory errors

Reference memory errors

DISCUSSION area of the open ﬁeld is usually considered as an index

Working memory errors

Male Female anxiety evidenced by increased

Reference memory erros

SD †† connecting barrel ﬁeld in the pri-

Apical dendrites - Female Apical dendrites - SD

Apical dendrites Basal dendrites

Apical dendrites - Female Apical dendrites - SD

A CA1 apical dendrite B CA1 basal dendrite

C CA3 apical dendrite D CA3 basal dendrite

30 Male Female Male Female Control

A CA1 region CA3 region

CA1 region CA3 region

(Received 19 June 2021, Accepted 5 November 2021)

You might also like