Extra class this Sat

 Time: 9am-12pm
 Venue: CG04
 Purpose:
 Revise and ask questions on SP222
 NOT compulsory attendance
 If you have NO questions to ask, DON’T COME
 Questions such as “What’s coming out for finals?” do not apply
Learning and Memory
SP222
Learning and memory

 Lashley’s search for the engram (physical representation of learning in the brain)

 Theorized that if someone learns something, there has to be a part of the brain
responsible for the learning
 Trained mice on mazes, then made deep cuts in various areas of the cerebral cortex
 No knife cut significantly impacted the learning and retention of the rats
 Suggested two principles about the nervous system:
1. Equipotentiality – all parts of the cortex contribute to learning
2. Mass action – the cortex works as a whole, and more cortex is better
Modern search for the engram

 Richard F. Thompson decided to see if he could find the engram

 Suggested that the engram was found in the cerebellum instead of the cerebral cortex
 Conditioned rabbits to blink whenever they played a sound
 Suppressed the lateral interpositus nucleus (LIP), which is essential for learning
 When LIP was suppressed, the rabbit couldn’t learn the conditioned response
 Then suppressed the red nucleus (a mid-brain motor area that receives input from the
cerebellum)
 Rabbits that had their red nucleus suppressed also didn’t react to the training, but the
moment the red nucleus recovered, the rabbits immediately displayed learned
behaviour
Memory

 Several different types of memory:

1. Working memory
2. Short-term memory
3. Long-term memory
Working memory

 A special kind of memory proposed by Baddeley and Hitch (1974; 1994) that is
like a ‘temporary storage’ of information while we work on it
 A common test of working memory is the delayed response task
 Requires you to respond to something you saw or heard a short while ago
 E.g. see a red light flash on top of one of several doors, waiting a few seconds, then
going to the correct door where the light flashed
 Seems to be stored primarily in the prefrontal cortex
 Many older people have impairments of working memory, likely due to changes
in the prefrontal cortex
Short-term memory

 Differs in capacity from long-term memory

 Short-term memory typically has less capacity compared to long-term memory
 ~7 items in the average human being
 Short-term memories fade quickly unless you rehearse them
 Rehearsal leads to memories being “transferred” from STM to LTM
 Once you forget something in short-term memory, it is lost
 Almost impossible to try to remember something that you didn’t rehearse
 E.g. carplate number you saw 5 minutes ago
Long-term memory

 Exact capacity of the long-term memory is unknown

 Memories in the long-term memory can be recalled even if they have not been
thought about for years
 Memories in long-term memory can be brought back using hints
 E.g. you can only name a few of your high school teacher’s names, but if shown a
picture and given hints about their initials, you can probably remember more
 Researchers propose that all memory initially enters short-term storage, where it
stays until the brain can consolidate it into long-term memory
Hippocampus and Amnesia

 Amnesia: memory loss

 People rarely suffer complete memory loss (still remember how to eat with a knife and
fork, etc)
 Hippocampal damage and Amnesia
 In 1953, a man known as H.M. suffered ~10 minor epileptic seizures per day and a
major seizure per week
 Eventually, his neurosurgeon removed his hippocampus from both hemispheres, trying
to cure it
 While he did have less seizures (1-2 major seizures per year), he also developed
retrograde and anterograde amnesia
H.M.’s memory functions

 Aside from developing retrograde and anterograde amnesia, there were also other
developments with H.M.’s memory
 H.M.’s working memory was still intact – could still remember a number given to him
10-15 minutes ago
 Impaired storage of long-term memory – can remember certain parts of history, but not
all
 Severe impairment of episodic memory – cannot describe any experience he has had
since his brain damage
 Better implicit than explicit memory
Theories of the function of the
hippocampus
 Three hypothesis of what the hippocampus is important for:
1. Declarative memory
2. Spatial memory
3. Context
Declarative memory

 Two types of memory:

1. Declarative memory – the ability to state a memory in words
2. Procedural memory – development of motor skills and habits (linked to the basal
ganglia)
 Patients with hippocampal damage have intact procedural memory (e.g. still know
how to ride a bike), but have impaired declarative memory
 Testing for declarative memory:
 Delayed matching-to-sample task
 Delated non-matching-to-sample task
Spatial memory

 Spatial memory – memory that is related to spaces

 When people are asked to perform spatial tasks (e.g. remembering how to get to KLCC
from home), activity is recorded in the hippocampus
 PET scans on taxi drivers from London based on spatial questions found that the
hippocampus was more active compared to non-spatial memory questions
 These taxi drivers also had larger than normal posterior hippocampus, suggesting that
more spatial learning experiences result in larger growth of the hippocampus
Testing Spatial Memory

 In order to test spatial memories in animals, two common methods are used:
1. Radial maze
2. Morris water maze task
Radial Maze

 Typically has 8 or more arms, with food placed in one or more arms
 Rats placed in the centre will typically explore each arm for food once and only
once
 Some variations create “rough floors” in certain arms that never have food, and
rats learn to never enter those never-correct arms
 Rats with hippocampal damage seldom enter never-correct arms, but often enter a
correct arm twice or more times
Morris water maze task

 Rats must swim through murky water to find a rest platform that is just under the
surface (so the rat cannot see it)
 Normal rats tend to find the platform and remember its location – when they are
placed back into the water, the move straight to the platform
 Rats with hippocampal damage never seem to learn where the platform is, and
constantly have to look for it again no matter how many times they’ve been put in
the maze
Context

 The hippocampus is also hypothesized to relate to contextual memories

 Think about what you learned yesterday in class – who was with you? Where were you
seated?
 In humans, recalling a recent memory (which usually involves details and
context) activates the hippocampus
 Testing in normal rats found that they remember better if placed in similar
contexts
 Rats with hippocampal damage showed no improvement in memory even if placed in
similar contexts
Hippocampus and consolidation

 People with hippocampal damage tend to have working short-term memories, but
impaired long-term ones
 Suggests problems with memory consolidation
 Different memories consolidate differently
 You probably cannot remember the historical fact you learned in school
 You probably can remember your first girlfriend/boyfriend in school (emotional
memories consolidate easier)
 Stressful or emotional situations release cortisol and adrenaline. Small to moderate
levels of cortisol activate the amygdala and hippocampus
Other types of amnesia

 Other diseases and environmental factors can contribute to amnesia and memory
loss:
1. Korsakoff’s syndrome
2. Alzheimer’s
Korsakoff’s syndrome

 A.k.a. Wernicke-Korsakoff syndrome

 Brain damage caused by prolonged thiamine deficiency
 Occurs mostly in chronic alcoholics who go for weeks at a time on a diet consisting of
nothing but alcohol, which have no vitamins (thiamine = Vitamin B)
 Prolonged thiamine deficiency leads to shrinkage of neurons in the brain, which particularly
affects the dorsomedial thalamus, the main source of input to the prefrontal cortex
 Symptoms of Korsakoff:
1. Apathy
2. Confusion
3. Memory loss
4. Confabulation – “filling in the gaps” in their memory by guessing
Alzheimer’s

 Alzheimer’s patients have better procedural than declarative memory

 Learn new skills, then are surprised that they are so good at it because they don’t
remember learning it before
 Memory and alertness vary substantially from one day to another, and one time to
another within the day
 Gradually progresses to more serious memory loss, confusion, depression,
restlessness, hallucinations, delusions, sleeplessness, and loss of appetite
 Affects 5% of people between age 65 and 74, and almost 50% of people aged
over 85
Comparison
of a normal
brain vs one
with
Alzheimer’s
Alzheimer’s

 Chromosome 21 contains a gene linked to many cases of early-onset of

Alzheimer’s
 Genes controlling early-onset of Alzheimers cause a protein called Amyloid-B to
accumulate both inside and outside neurons, and high levels of these damage
axons and dendrites
 These damaged structures cluster into plaques, and as the plaques increase, the
cerebral cortex, hippocampus, and other areas begin to atrophy (waste away)
 Abnormal accumulation of tau proteins (part of intracellular support structure for
neurons) produces tangles (structures formed from degenerating structures within
neuronal bodies), which also contribute to Alzheimer’s symptoms
The role of other brain areas in memory

 Amygdala has been found to be particularly important for fear learning

 Parietal lobe – important for associating one piece of memory with another
 Damage to the Anterior and inferior regions of the temporal lobe – results in
semantic dementia (loss of semantic memory)
Storing information in
the Nervous System
Concept of the Hebbian synapse

 When the axon of a neuron (Neuron A) repeatedly activates another neuron

(Neuron B), the connection becomes stronger, and Neuron A can therefore
activate Neuron B easier
 Discovered by Donald O. Hebb, who gave it the name “Hebbian synapse”
Studying invertebrates to determine
learning
 Studying a human or mammal, with lots of neurons, can make it difficult to
properly determine how learning takes place and how information is stored
 As a result, scientists study invertebrates, which have far fewer cells (some are
even single-celled), but have similar neurons, principles of action potential, and
even neurotransmitters
Studies on Aplysia

 Aplysia is a marine invertebrate related to

the common slug, and is a popular animal
for studying the physiology of learning
 Has far fewer neurons, which are also large
and easy to study
Habituation in aplysia

 Habituation – a decrease in response to a stimuli that is presented repeatedly and

accompanied by no change in other stimuli
 E.g. a clock that rings every hour – you eventually respond to it less and less, and
eventually don’t even realise it’s rung
 In habituation, the sensory and muscle neurons do not change in their responses –
so it’s not about muscle or sensory neurons
 Habituation seems to depend on a change in the synapse between the sensory neuron
and motor neuron
Sensitization in Aplysia

 Sensitization – an increase in response to mild stimuli as a result of exposure to

more intense stimuli
 Experiencing an unexpected, intense pain causes you to temporarily react more
strongly to other strong, sudden stimuli
 Sensitization is traced to changes at identified synapses
 Strong stimulation excites a facilitating interneuron, which releases serotonin onto the
presynaptic terminals of many sensory neurons
 This serotonin blocks potassium channels in the membrane, delaying neurons from re-
uptake and prolonging the release of neurotransmitters, causing the post-synaptic
neuron to be more sensitive for a short period of time
Long-term potentiation in vertebrates

 Long-term potentiation: one of more axons connected to a dendrite bombard it

with a brief but rapid series of stimuli – e.g. 100 per second for 1 – 4 seconds
 This burst of intense stimulation leaves some synapses potentiated (more responsive
to new input of the same type) for minutes, days, or even weeks
LTP as the cellular basis for learning and
memory
 Importance of LTP to learning and memory:
1. Specificity – if some synapses onto a cell are highly active while others are not,
only the active one becomes strengthened. However, establishing LTP at one
synapse briefly facilitates the formation of LTP at other nearby synapses on the
same dendrite
 Cooperativity – nearly simultaneous stimulation by two or more axons produces
LTP much more strongly than repeated stimulation by just one axon
 Associativity – pairing a weak input with a strong input enhances later response to
the weak input (Hebbian synapses)
Long-term depression (LTD)

 The opposite of LTP

 A prolonged decrease in response at a synapse
 Happens when axons have been less active than others
 Required to compensate for stronger synapses – if all our synapses only grow stronger
and never weaker, our brain will require more and more fuel to function