Medizinische

Fakultät

Department for Otolaryngology-Head and Neck Surgery

Sensory Neuroscience
André Deutschmann
Department of Otolaryngology, Head & Neck Surgery
University of Tübingen Medical Center

[email protected]
 Medizinische
Fakultät

Housekeeping
The final grades will be composed of three parts:
1. Exam: after 8 lectures, counts 50% of final grade (18.12.23)
2. Homework: max. 2 points per homework (only in first 8 lectures; 16 points total → best grade),
counts 20% of final grade
3. 3) Essay: Every student will write one essay to a topic related to the lectures given in
January/February, 1.5 to 2 pages (800 – 1100 words), counts 30% to final grade, every lecturer
suggests ~ 10 topics, which will be presented and distributed on 11th of December. Deadline
for essay submission: 5th of February.

❖ Desired topic:
Please submit suggestions for topics until 8th of January to L. Rüttiger or E. Reisinger
The decision will be made by the students on the 15th of January
 Medizinische
Fakultät

Somatic senses – General senses

•Skin •Touch/pressure
•Muscle •Temperature
•Joints •Pain
•Viscera •Proprioception
 Medizinische
Fakultät

Special Senses

• Smell Odor
• Vision Light
• Hearing Sound
• Taste Buds Taste
• Equilibrium Movement
 Medizinische
Fakultät

How Does a Stimulus Get Reported to the Brain?

Medizinische
Fakultät

Ion Channels
 Medizinische
Fakultät

Ion Channels
Hydrophilic pores across membranes
Transport of inorganic ions
Ion selectivity
Main ions are Na+, K+, Ca2+, Cl-
Up to 100 million ions/s
- 105 times faster than carriers or pumps
- Transport is always passive -> no energy needed
- Have to shed most of their associated water molecules

Ackermann et. al 1997

Chem.libretexts.org
Designua / Shutterstock
 Medizinische
Fakultät

Ion Channels
Hydrophilic pores across membranes
Transport of inorganic ions
Ion selectivity
Main ions are Na+, K+, Ca2+, Cl-
Up to 100 million ions/s
- 105 times faster than carriers or pumps
- Transport is always passive -> no energy needed
- Have to shed most of their associated water molecules

Ackermann et. al 1997

Chem.libretexts.org
Designua / Shutterstock
 Medizinische
Fakultät

Ion Channels
Most ion channels are gated
- Ligand-gated
- Nucleotide-gated
- Voltage-gated
- Mechanically-gated
Modified through posttranslational modifications
- Phosphorylation
G-protein

Chem.libretexts.org
Amos Bairoch
 Medizinische
Fakultät

Potential Gating Mechanisms for Mechanically Sensitive Ion Channels

Surface tension or bending of the lipid bilayer

Tether model

Indirect tethers

Secondary signal such as a diffusible second-messenger

 Medizinische
Fakultät

Ion Channels
Most ion channels are gated
- Ligand-gated
- Transmitter-gated
- Nucleotide-gated
- Voltage-gated
- Mechanically-gated
Modified through posttranslational modifications
- Phosphorylation
G-protein
Chem.libretexts.org
Amos Bairoch
 Medizinische
Fakultät

Membrane Potential

Differences in electrical charge (two sides of a membrane)

Generated by ion flux and pumps
K+ movement creates an electrical force-> membrane potential
Equilibrium conditions -> no net flow of ions across the membrane resting
membrane potential

Molecular Biology of the Cell. 4th edition

 Medizinische
Fakultät

How to Generate a Membrane Potential?

Typical neuron
~150 mM Na+
~5.4 mM K+
~80-140 mM K+
Na+/K+-ATPase
~ 4-12 mM Na+
K+-channel
-70 mV
equilibrium
potential

extr. Space = 0 V
 Medizinische
Fakultät

Equilibrium Potential
Potential difference that balances a concentration
gradient for a certain ion
The greater the concentration difference the greater the
potential
In most cells K+ equilibrium potential is close to the
resting membrane potential
- Resting membrane is more permeable to K+ than Na+
- Na+/K+ -ATPase maintains the concentration gradient

Blausen.com staff (2014)

 Medizinische
Fakultät

Nernst Equation

Equilibrium relation between concentration ratios and energy differences

Calculation of the theoretical resting membrane potential
-> using Nernst equation
 Medizinische
Fakultät

Nernst Equation
[C]o Ion concentration extracellular

𝑅𝑇 [𝐶]𝑜 [C]i Ion concentration intracellular

𝐸= ∗ ln
𝑧𝐹 𝐶𝑖 R= Universal gas constant (8.314 J/(K*mol))

61 [𝐶]𝑜 T= absolute Temperature (Kelvin)

𝐸= ∗ 𝑙𝑜𝑔10
𝑧 𝐶𝑖 z = ion charge (e.g.1 for K+ and 2 for Ca2+)

F= Faraday’s Constant
4
-92 mV= 61 ∗ 𝑙𝑜𝑔10
126

Nernst equation for Potassium

 Medizinische
Fakultät

Nernst Equation

Intracellular
Overall direction of Extracellular
Ion Overall impact on resting potential concentration Ratio outside/inside
movement concentration (mM)
(mM)

Potassium Extracellular Makes it more negative 4 126 0.031

Sodium Intracellular Makes it more positive 145 12 12

Makes it more negative (small

Chloride Intracellular 120 4 30
impact)

Makes it more positive

Calcium Intracellular 2 0.0001 >10,000

4
-92= 61 ∗ 𝑙𝑜𝑔10 Nernst equation for potassium
126
 Medizinische
Fakultät

Summary

Resting membrane potential is mainly driven by K+ ions

By using the Nernst equation, the theoretical equilibrium potential of ions
can be calculated
Ion channels are ubiquitously distributed throughout cells
Ion channels are crucial for cell activity
Medizinische
Fakultät

Receptor Potential
 Medizinische
Fakultät

Receptor Potential
• Depolarization of the receptor membrane
• Due to proper stimulation
• Non propagated depolarizing potential (no action potential)

https://doctorlib.info/
Medizinische
Fakultät

Action Potential
 Medizinische
Fakultät

Action potential

courses.lumenlearning.com
 Medizinische
Fakultät

Action Potential (AP)

Electrical excitation
Directly related to the properties of voltage gated ion channels
Frequency of AP depends on the strength of the depolarizing current
Threshold
Carries signals without attenuation
Speed: 100m/s

http://fblt.cz/en/skripta/regulacni-mechanismy-2-nervova-regulace/2-obecna-neurofyziologie/
 Medizinische
Fakultät

Action Potentials
 Medizinische
Fakultät

Myelination of Neurons
Interrupted by nodes of Ranvier
Nodes of Ranvier concentrate all
Na+ channels

Depolarization spreads from node to node

- Faster AP traveling and energy saving

Giuliodori et al 2004
 Medizinische
Fakultät

Structural Receptor Types

Lumenlerning.com
 Medizinische
Fakultät

Primary Sensory cells

Receptor membrane is part of a neuron

https://mammothmemory.net/
 Medizinische
Fakultät

Secondary Sensory cells

The receptor is a specialized sensory cell

 Medizinische
Fakultät

Synaptic Transmission

Depolarized Membrane

Receptor Potential and

Action Potential

Bruce et al 2018
 Medizinische
Fakultät

Sensory Receptors
• Transducer that converts different types of stimuli into voltage changes/action
potentials

• Usually only sensitive to a specific form of stimuli

 Medizinische
Fakultät

Types of Sensory Receptors

• Usually specialized
• Excitable cells
• Signal transmission to other nerves
• Special receptor protein
 Medizinische
Fakultät

Transient Receptor Potential (TRP) Channels

• Evolutionarily conserved integral membrane proteins
• Mediate a vast array of different cellular and organismic sensation
• TRP channels are a class of cationic channels that act as signal
transducers
• Involved in
✓ Mechanosensation
✓ Chemosensation
✓ Thermosensation
✓ Olfaction
✓ Taste

Christensen et al 2007
 Medizinische
Fakultät

Sensory Receptors
• Thermoreceptors
• Nociceptor
• Photoreceptors
• Chemoreceptors
• Mechanoreceptors

• Especially sensitive kind of neuron

• Detect changes of 0,01°C
• Expression of TRP-channels in the neuron membrane
defines sensitivity for cold or warmth

Channel activity
Temperature °C
 Medizinische
Fakultät

Sensory Receptors
• Thermoreceptors
• Nociceptor
• Photoreceptors
• Chemoreceptors
• Mechanoreceptors
 Medizinische
Fakultät

Sensory Receptors
• Thermoreceptors
• Nociceptor
• Photoreceptors
• Chemoreceptors
• Mechanoreceptors

Britannica.com
 Medizinische
Fakultät

Sensory Receptors
• Thermoreceptors
• Nociceptor
• Photoreceptors
• Chemoreceptors
• Mechanoreceptors

Britannica.com Biorender
 Medizinische
Fakultät

Sensory Receptors Taste buds

• Thermoreceptors
• Nociceptor
• Photoreceptors
• Chemoreceptors
• Mechanoreceptors
 Medizinische
Fakultät

Sensory Receptors Taste buds chemoreceptors

• Thermoreceptors
• Nociceptor
• Photoreceptors
• Chemoreceptors
• Mechanoreceptors
 Medizinische
Fakultät

Summary Sensory Receptors

• Receptors convert different types of energy into an electric signal

• Occur in specialized organs

• Depend on ion channels

• Direct or indirect signal transduction

• Primary or secondary sensory cells
Medizinische
Fakultät

Mechanosensation
 Medizinische
Fakultät

Touch Sensation in Nematodes

Christensen and Corey 2011

 Medizinische
Fakultät

Mechanosensory Organs in the Fruitfly

bristles and segmented antennae

 Medizinische
Fakultät

Superficial Lateral Line

• Lateral line receptors consist of the same sensory hair cells as found in the ear
• hair cells are organized into small groups called neuromasts
 Medizinische
Fakultät

Hair Cells Specific Mechanoelectric Transduction

 Medizinische
Fakultät

Hair Cells in the Auditory and Vestibular System

Blausen.com staff (2014)

 Medizinische
Fakultät

Hair Cells in the Auditory and Vestibular System

Hair cells in the cochlea:

Outer hair cells (OHC)

Inner hair cells (IHC)

Blausen.com staff (2014)

 Medizinische
Fakultät

Hair Cells in the Auditory and Vestibular System

Blausen.com staff (2014)

 Medizinische
Fakultät

Hair Cells in the Auditory and Vestibular System

Hair cells in the vestibular epithelia (VHC):

Vestibular

Typ I
Typ II

Blausen.com staff (2014)

 Medizinische
Fakultät

Hair Cells in the Auditory and Vestibular System

Hair cells in the cochlea: Hair cells in the vestibular epithelia:

Typ I

Outer hair cells TypII

Inner hair cells

 Medizinische
Fakultät

Stereocilia Hair Bundle

Outer Hair Cells Bundles Inner Hair Cells Bundles Vestibular Hair Bundles
 Medizinische
Fakultät

Stereocilia and Tip-links

• Tip link
• Connect Stereocilia
• Essential element of the mechanoelectrical transduction
• Extends from the tip of each stereocilium to the side of its tallest neighbor
 Medizinische
Fakultät

Auditory and Vestibular Hair Cells

 Medizinische
Fakultät

Pore Properties of the MET Channel

• Open or close according to the deflection

• Non-selective channel
• At the tip of stereocilia
• Opens in 40 µs

Peng et al.m nature reviews 2011

 Medizinische
Fakultät

Pore Properties of the MET Channel

• Open or close according to the deflection

• Non-selective channel
• At the tip of stereocilia
• Opens 40 µs
 Medizinische
Fakultät

Hair Bundle and Mechanosensitivity Develop Along Similar Time Frames

stereocilia (blue)

Peng et al.m nature reviews 2011

 Medizinische
Fakultät

Hair bundles and MET vary between hair bundle types

• Differences arise from the different functions of the hair

cells
• IHC

Peng et al.m nature reviews 2011

 Medizinische
Fakultät

MET channel properties in different cell types

Medizinische
Fakultät

The Vestibular System

Medizinische
Fakultät

Ruth Van Hecke et al 2021

 Medizinische
Fakultät

Vestibular System

• Linear acceleration (gravity)

• Angular acceleration
• Deceleration

• 5 receptor organs:
• Utricle: horizontal movements
• Saccule: vertical movements
• Three semicircular canals: angular shifts of
head position

Blausen.com staff (2014)

 Medizinische
Fakultät

Vestibular system
Utricle

Calretinin Sox-2

R.Arora

Jiang et al. 2021

 Medizinische
Fakultät

Vestibular System
Medizinische
Fakultät

Auditory System
 Medizinische
Fakultät

Organ of Corti Structure

 Medizinische
Fakultät

Synaptic Transmission in Inner Hair Cells

 Medizinische
Fakultät

The Effect of Hair Cell Deflection on Transmitter Release and Nerve Activity

Hair cell deflection

Receptor potential
depolarization hyperpolarization

I I I I I I I I I I IIIIIIIIIIIIIIIIIIII I I I I I I I I I I I I I I IIIIIIIIIIIII
Increased firing rate decreased firing rate
Neural spikes
 Medizinische
Fakultät

Summary
• Hair cells in the vestibular and the auditory system are involved in
mechanosensation
• The structure and organization of Stereocilia are important for
mechanotransduction in hair cells
• Tip links are associated with MET channels
• Tip link conveys tension force to the MET channel which leads
to channel opening
 Medizinische
Fakultät

Thank you for your attention

Questions:

1: What is the difference between primary and secondary sensory cells?

2: Describe the principle of mechanotransduction.

3: What is the difference between action potential and receptor potential?

Please submit by the 23rd of October, thanks!

Please don’t forget to write your name on the document.