Start: Neurobiology 302

http://courses.washington.edu/psych333/handouts/coursepack/ch10-Somatosensory_system.pdf

Somatosensory: 1) What? Catch-all term to designate senses other than vision, hearing, balance, taste, and smell.

a. Receptors distributed all across the body.

Types of Mechanoreceptors: Simple Neural Coding/Knee Jerk: Muscle spindle sensory neuron branch to motor (excite/contract

quad) and flexor (inhibit in ham)

http://www.ifc.unam.mx/Brain/reflex.htm

1) Kneejerk Reflex: Tapping the knee pulls the tendons of quadriceps.

a. When this muscle stretches, information in the form of APs goes down (1) through

the sensory neuron. This is because the stretch-sensitive receptors (spindles) are

excited. This spindle is innervated by the 1a afferent fibers, which lead to the spinal

cord.

b. Sensory neurons synapse with extensor and flexor motor neurons in the spinal

cord.

i. Extensor/Excitatory: Contracts the quadriceps, the muscle that was

stretched.

ii. Flexor/Inhibitory: Inhibits flexor muscles that would contract the

hamstring.

Frequency Coding: Linear relationship when transducing from intensity to frequency.

Concept of Receptive Field:

1) Definition: Location or sensory space in which a stimulus will elicit a response from the

neuron.

a. Example: Any part of skin that, when stimulated, will elicit a response from that

receptor.

2) Each sensory system has its own definition of receptive field.

Somatosensory Submodalities: 1) Definition: Specific sensations encoded by the somatosensory system.

a. Modality simply means stimulus type.

1) The submodalities are mediated by dorsal root ganglion cells, which are where the cell

bodies are located.

a. These dorsal root ganglion cells are composed of similar-type cells that act as the

sensory neurons for the somatosensory system.

2) These cells are bipolar:

a. One axon goes to the periphery (skin, muscle, joint capsules, etc.) with specialized

receptors for specific types of stimuli.

i. This axon is ‘dendrite-like’ in that it receives information from the outside

world, but it isn’t actually a dendrite.

ii. Note that there’s a freely branching ending at the end of the periphery

axon.

b. Second axon goes to the CNS through the dorsal root of the spinal nerve.

3) Both of these axons are myelinated for really fast conduction.

4/1: Mechanoreceptors in the Skin: Tactile sensations in the human hand arise from four kinds of mechanoreceptors: Meissner corpuscles (RA1 - low frequency/amplitude (light) skin motion – lateral hand motion across objects … makes sense because upper layer/light touch) Merkel cells (SA1 – edges and points – slowly adapting so good for detecting constant pressure), Pacinian

corpuscles (vibration – rapidly adapting good at distinguishing frequency changes – on off on off), and

Rufini endings (SA2 – stretching is a constant pressure, good for slowly adapting)

Summary:

Corpuscles/Rapidly Adapting (1 is epidermal, 2 is deeper, dermal).

Misses’ go first.

1) Hairy Skin: Nerve terminals are wrapped around the base of each hair.

a. Hair motion is encoded based on direction and intensity.

Our focus is on the Glabrous Skin (Smooth Skin):

There are several different types of mechanoreceptors (touch receptors) in the skin.

1) Unmyelinated Nerve Endings (1): Unmyelinated nerve endings can go to many different

places and are involved in chemical inputs and pain.

2) Epidermis:

a. Meissner Corpuscle (RA1): Unmyelinated nerve endings can attach to the

Meissner Corpuscle.

b. Merkel Disc Receptor (SA1): “ “ can attach to this as well.

3) Dermis:

a. Unmyelinated endings can also attach to the Ruffini Endings (SA2) or Pacinian

Corpuscle (RA2).

4) Recall that the other side of the myelinated axon goes over to the CNS (other side of the

peripheral nerve bundle).

Meissner and Merkel:

1) Recall these are the ones located in the epidermis.

2) Meissner Corpuscle (RA1): This is the receptor organ a globular, fluid-filled structure of

flattened cells with nerves between the layers.

a. Rapidly Adapting: If we record from the nerve and stimulate as a ramp function,

we see that the receptors soon stop generating APs.

3) Merkel Cell (SA1):

a. Rigid structures that transfer strain from surface to nerve ending.

b. Slowly Adapting: If we record from this cell, a constant stimulus will not lead to

adaptation. It will thus continue to respond to pressure for as long as it is sustained

(within a reasonable time frame).

c. Use: Edges/corners/points.

Pacinian Corpuscle and Ruffini: 1) These are located in the dermis, deeper layer.

2) Pacinian Corpuscle (RA2): Large, onion-like capsule.

a. Rapidly adapting, so we stop firing as soon as the indentation is stationary.

3) Ruffini Endings (SA2): Primarily excited by stretching – can tell how much stretching is

on the hand after holding an object, for example.

Concept of Best Frequency:

1) What? Idea that each receptor is most sensitive to stimulation at its natural or best

frequency.

2) Merkel Cell vs. Meissner Corpuscle:

a. When we push on the corpuscle, the structure itself moves in response, but we

adapt quickly.

b. By the frequency encoded, we can determine if something is moving or sustained.

c. Example: Bug moving around on your finger. This is encoded by the Corpuscle (RA)

as a rapidly adapting response that soon turns off. It detects change in position of

the bug.

i. On the other hand, the Merkel (SA) will detect that the bug is still there

(motionless). Remember it is slowly adapting, so it can detect deformation of

the skin (pressure).

Receptive Fields of Mechanoreceptors:

1) What? Individual mechanoreceptors convey information to a limited area of skin called

the receptive field.

2) How? Mapped by recording from median nerve and stimulating hand with different

sizes/strengths of stimuli.

Superficial vs. Deep Layers Comparison:

1) Superficial (Type 1): Relatively small receptive field consisting of small spots.

a. Graph C shows a zoomed in version of the receptive field of a single fiber/corpuscle.

2) Deeper (Type 2): Innervate deeper layers

a. Activated when you press deeper on the skin.

b. Differences: Receptive field has one hot spot whose sensitivity is greatest (located

directly above receptor) with an overall wider arc surrounding this hot spot.

i. Possibility for overlap of inputs with other nearby Pacinian corpuscles.

Rapidly Adapting Pacinian Corpuscle:

1) Corpuscle: Made of connective tissue; the unmyelinated part of the RA2 fiber is located

inside. 2) Response: when sustained input/pressure is applied, the RA2 fiber fires a burst at the

start and end of stimulation

a. Why? At the beginning, the connective tissue deforms and then quickly adapts

to the stimulus. So, the underlying nerve stops feeling the pressure and stops

firing. When we take this stimulus off, we redisturb the tissue and underlying

nerve, making it fire at the end.

i. Contrast to sinusoidal firing (vibration), which causes a continuous

firing – no adaptation because not constant (vibration-like).

Experiments on Pacinian:

1) This shows that the rapidly adaptation of the Pacinian is wholly due to the physical

surroundings of the nerve endings: the connective tissue surrounding the nerve fiber is

what causes the rapid adaptation.

a. We have a sustained receptor potential when the connective is removed (no

adaptation).

1) Y-Axis: Amplitude of the vibration.

2) Left Graph: Shows that the best frequency is around 200 Hz for the RA2 fiber.

a. We only need a small amplitude vibration for a person to notice something

happening.

b. At lower frequencies, say 10 Hz, it requires more amplitude to feel something going

on.

3) Right Graph: What a person actually perceives in a situation is exactly the same as taking

all of the mechanoreceptors and looking at the most sensitive receptor at each frequency.

The ‘real’ frequency matches the most sensitive frequency.

Two-Point Threshold:

1) What? Measures the minimum distance at which two stimuli are resolved as distinct.

a. We use two prongs to touch various parts of the body.

b. For example, we would feel two distinct prongs if we touched the fingers (smaller

threshold) vs. the back (would feel only one).

c. The fingers, lips, soles of feet are most sensitive (receptive field smallest).

i. More receptors in smaller receptive field.

ii. More receptors means better ability to discriminate two points.

2) A place on the body that is more sensitive has a smaller threshold for distinguishing two

points. At any distance above that threshold, we would distinguish two points. Anything

smaller than that we would only smush it to one point.

4/2: KCNQ4 and Somatosensory Continued

1) SA1 Merkel: Most distinct and fine. Nerve fires only when moving over the dots and is

silent in the spaces (no stimulation).

a. Receptive field smaller than the size of dots each dot stimulates a new set of

SA1 fibers.

2) RA1 Meissner Corpuscle: not as good at distinguishing because of larger receptive

fields.

a. Function: Can tell whether something is present or not present.

3) RA2/Pacinian Corpuscle: Good at detecting vibrations, although there is no

discrimination – receptive fields too large.

4) SA2/Ruffini: Receptive fields also too big.

KCNQ4: 1) There are many different types of K channels – we’re going to focus on the KCNQ4.

2) Normally, the resting K channels are important because they set resting conductances for

the neuron.

3) The KCNQ4 regulates cell excitability because it modulates membrane potential in cells

where it’s expressed.

The M Channel (blocked by Muscarine – Ach agonist)

1) Ionotropic Ach channel (fast EPSP) and then we get a slow EPSP (Ach activated a

metabotropic receptor second messenger system to close M-type K channel).

2) If we close these M-type K channels, we make the cell more excitable because we are taking

away the resting channels (threshold more negative).

a. Graph C shows this.

1) Graphs plot value of current vs. each held voltage.

a. The I-V curve is shifted extremely negative.

b. The M-current turns on at -50 mV (resting potential of most cells).

c. This M current sets excitability of the cells. It is open near rest.

1) Block M current lower resting conductance, so the cell becomes more excitable.

Recall: At hair follicle mechanoreceptor, we deform free nerve endings (unmyelinated), physically

changing membrane which opens up ion channels, depolarizing and making APs fire.

KCNQ4 Channels in Mouse: NF200 stain axons, KCNQ4 stains for itself.

1) Hair follicle: Free unmyelinated endings wrap around the follicle.

a. Coexpressed KCNQ4 and axons in the unmyelinated endings.

b. Coexpressed in the corpuscle or in the hair follicles.

1) Apply ramp of indentation to the messiner corpuscle:

2) Wild Type vs. Mutant: In mutant, we take out K channel more excitable

hyperexcitable mutant cell doesn’t adapt as well as the wild type.

1) Humans also have the KCNQ4 expressed in the hair follicle. However, some people do not

have this expressed – they are deaf.

2) In a) we apply a frequency of stimulus that continually increases. We ask when they feel the

stimulus.

3) KCNQ4 is expressed around hair follicle and Messiner – not found in Pacinian.

a. What does this do?

i. Frequencies felt by Pacinian are not changed – no KCNQ4

ii. Frequencies in hair follicle/messiner – the individuals without KCNQ4 are

better able to notice stimulus – lower amplitude threshold for a given

frequency (more sensitive and excitable/more negative threshold).

iii. More sensitive (require smaller amplitude stimulus) to low frequency

events.

Spinal Cord: Question: What happens to the signals after they hit the mechanoreceptor?

1) Conduction velocities correspond to different nerves in a bundle.

2) X-Axis is conduction velocity.

a. C fibers conduct slowly because they are unmyelinated – involved in pain.

3) In the others, we have a 6x relationship between diameter and velocity (myelinated).

a. Cold and hot temperature/pain pathway (A delta)

4) Mechnoreceptor (A beta) – 12 72 diameter/velocity. We’ve been talking about these –

the peripheral mechanoreceptors.

a. Found in cutaneous nerves.

5) A alpha: large, muscle spindle

Spinal Anatomy:

1) 31 pairs of spinal nerves

2) Throacic (trunk)

3) Lumbar, sacral (Legs)

4) Spinal nerves are paired: one on left and one right.

5) Each dorsal root innervates a segment of skin of the animal – segmented dermatome.

a. Shingles dermatome.

1) Mechanoreceptor signals come in the spinal cord at the dorsal root ganglion and diverge

in two ways:

a. Sensory Neuron Motor Neuron: Tells the muscle that sent the signal to move.

b. Brain Stem: Higher up signal processing.

4/4: Anatomy of Spinal Cord/CNS:

This figure shows how somatosensory inputs are translated up to the brain stem.

1) Axons of motor neurons are preprogrammed during development to seek out the ventral exit

point (ventral roots) periphery to target muscles.

2) Dorsal Root contains the central and periphery projections.

a. Once axons from periphery enter dorsal root branch to motor neurons (where exactly

depends on modality of stimulus) OR

b. Can branch to the ascending (labeled 2a) go up dorsal columns to the brain stem.

3) The modality of stimulus is encoded in the mechanoreceptor itself. It is then “faithfully

transmitted” from the periphery into the CNS through axons.

a. The axons are ‘passive railways’ for the signals to pass through after encoded by the

receptor.

Anatomy of Spinal Cord: 1) The Honda-shaped structure that I outlined has dark blotches that are cell bodies (grey

matter).

2) The surrounding white matter consists of axons (myelinated axons appear white).

3) The upper splotches are interneurons that receive sensory information and project the

signal to the brain stem.

1) Grey: White Matter Ratio Increases ROSTRAL CAUDALLY: There is more white matter

(axon-containing parts) in the cervical because the axons that start in the lumbosacral

(gracilus fasciulus) continue up past into the cervical, taking up space in the white matter +

the new white matter from the cunenate fasciulus (cervical).

a. Lumbosacral: Just axons from there!

b. Cervical: Axons from lumbosacral AND axons from cervical area means more white

matter (outside part) and less grey matter.

A) Receptors land in different layers of the spinal cord (I- X) – each class of DRG finds its way to a

specific portion of motor neurons.

1) Cervical/Lumbar vs. Midthoracic: There is more grey matter in the cervical portion because

that’s where the limbs (specifically, arms) are located than in the thoracic (trunk).

2) Consequently, we get more motor neurons located in the cervical more grey matter.

Dorsal Column Medial Lemniscal Pathway:

1) Move from dorsal part of the spinal cord to the medial-lemniscal.

2) Pathway: Finger with mechanoreceptor (input) dorsal root ganglion one axon

branches to the motor neurons, one axon goes to dorsal (brainstem) medulla and cross

over (decusses to the other side) to become the medial lemniscus axons go to

thalamus.

What is the Thalamus? Also called ventral posterior nucleus

1) Thalamus is the waystation nucleus for our senses.

a. Functions to deliver signals to different parts of the cortex depending on the type of

stimulus (pain, visual, mechanosensory, etc.)

b. Codes for type of sensory stimuli, where it was in our body, and what type of response is

required.

__

Next Step: Reassembly at the Cortex.

2) Sensory information relayed to the cortex by the waystation thalamus.

a. Various types of info are laid out and segregated and joined again in cortex.

b. Types of sensory information are sorted out by the thalamus and relayed/put back

together in somatosensory cortex (S1).

i. Inputs from thalamus go to S1, A1 (auditory), V1 (Visual)

Anatomy of the Brain: Four Regions 1) Occipital (visual input and processing)

2) Temporal Lobe (auditory, speech)

3) Parietal Lobe (Somatosensory inputs land here)

4) Frontal Lobe (Plan movement in front portion, execute movement as you move back).

Anatomy of the Cortex:

Three Cortexes: Primary (sensory), Motor, and Association Cortex

1) The cortex is like a cloak that lies on the very top part of the brain.

a. The cortex consists of grey matter (cell bodies).

b. Everything else is white matter (axons).

2) All the units of the cortex are linked together via axons. Axons can travel long distances

from the cortex or short distances.

1) The Cortex is Striated: This physical striation reflects the fact that sensory information is

sent by thalamus to specific part of cortex. The information lands in different

layers/striations.

2) The Cortex has Six Layers (Applies to all three types of cortex):

a. I is very small in adulthood (outer layer of the brain)

b. Primary Sensory Cortex:

i. Layer Four is the input layer. The cells in layer four are accepting input and

project to the other layers of cortex. The layer is broken up into sublayers

(A, B, C).

1. So, it is the largest layer because it takes in a lot of information.

ii. The other layers are projection neurons that send information to other

parts of the brain.

c. Primary Motor Cortex:

i. Very small IV layer, but V and VI have huge cells (Betz cells - motor

neurons) that might make a twitch in the finger if we stimulate this area of

the cortex.

1) We get lighter moving from primary sensory cortex to association cortex because

there are fewer cell bodies in that area. Recall layer four in sensory had a lot of stuff,

association has less (no stripe).

a. Notice the really dark portion in the sensory – that’s layer IV.

b. This is conserved throughout the visual, somatosensory, and auditory system.

The layer IV is always denser because that’s where the axons input.

Somatosensory in Detail:

1) Note the layers – that is where we would see the layers we talked about earlier.

2) Central sulcus divides motor and somatosensory cortex.

3) Inputs coming in from dorsal column are laid out in the cortex. They are arranged in regions (3,

1, 2) based on where it comes from in the body and its modality

a. Note 3a and 3b are wrapped around the sulcus (dips inward).

4/7: Somatosensory Details

Note: This figure shows the area of the cortex dedicated only to one middle finger (see below

figure).

1) Recall: Each mechanoreceptor detects a different modality (type of touch – vibration,

pressure, etc.)

a. We separate the inputs in the thalamus by modality and location of input and then

reassemble this information in the cortex.

2) Region 5: “Active Touching” is responsible for “actively” trying to figure out what

something is.

3) Different mechanoreceptors are sent to different regions of the cortex.

4) Convergence of Information to Area 2: Neurons within 3a, 3b, 1 send their axons to each

other through the white matter (for example, see an arrow that goes from 3a to 2).

a. All inputs from muscle spindles, sa1, ra1, ra2 all end up at area 2.

5) Figure B/Receptive Field Size: The receptive fields get larger because we’re adding more

information from more receptive fields – we are summating the receptive fields.

a. After combining the info in region 2, the cortex can identify can determine

attributes of the object.

Close-up of digit 3 AKA middle finger.

1) The inputs initially land in layer IV and are then sent to different regions. The axons in layer

IV then synapses with projection neurons, which are then sent to section 2 in the cortex

(see last figure).

2) Note that the fingers are organized right next to each other on the cortex (zoom in figure A).

a. The fingers are represented in both section 3b and section 1 – they are both input

layers.

1) Different parts of the body is partially represented in many different places.

2) Cortical Amplification: More cortex is dedicated to the fingers vs. the torso because there

are many more mechanoreceptors in the fingers vs. torso.

1) The somatosensory map represents how much cortex is dedicated to each part of the body.

2) This is composed of a cross section of the somatosensory cortex.

3) More mechanoreceptors and smaller receptive field in the larger “pieces”

a. Smaller receptive field means more densely packed axons, meaning more axons

going to the cortex.

1) Example: Playing piano. We can compare before vs. after training. The digit that got the

most training has more representation in the cortex.

a. The receptive fields are also smaller.

1) Example: Removing Limb. We get phantom responses. This is caused by rearrangement

of cortical circuits.

a. Adjacent fibers expand. Now, this place that used to be innervated by axon fibers

from the hand are innervated by other parts of the skin.

b. Brain interprets activity from face/upper arm as from the amputated limb.

Comparative Physiology:

1) Vibrissae: Nocturnal rodents use this mechanoreceptor for whisking – tells the rodents

what kind of stuff they’re walking in.

a. Each vibrissae represented on somatosensory – vibrissae highly represented in S1

b. Each hair has innervating nerve endings that go through the typical pathway

through thalamus and cortex.

2) Staining in the second figure shows where oxygen is being used. We can see the barrels of

vibrissae, all of which land in layer IV.

The Star-Nosed Mole:

1) The nose has a star on it! There are mechanoreceptors on the rays.

2) Receptive fields near the middle (1 and 11) are the most sensitive – allows mole to

determine what it has is food and if so, it will eat.

3) The other rays consist of mechanoreceptors (free nerve endings) with Merkel cells below,

then something resembling a Pacinian Corpuscle below that.

a. Myelinated nerves go through the typical pathway to the thalamus then

somatosensory cortex.

1) Fastest vertebrate eater in the world!

4/8: Pain Pathways

1) Pain is mediated by nociceptors, made of free nerve endings of primary sensory neurons.

2) Largest axons are the A alpha and A beta, followed by A delta then C fibers.

3) Result: When we experience pain, we have two types of pain.

a. The first is the sharp pain. This is transmitted by the A deltas.

i. The A alpha/beta are just detecting change in skin, no pain involvement.

b. The second is the more prolonged, burning pain.

i. Mediated by the C fibers.

1) Minor shock: A Alpha activated, fastest conduction velocity but barely perceived.

2) Medium Shock: A alpha and A beta (mechanoreceptors recruited).

3) Strong Shock:: A delta added on (sharp pain)

4) Strongest: C fibers activate later, causing the burning pain.

1) TRP (Transient receptor Potential) ion channels convert noxious stimuli energy into a

depolarizing electrical potential.

a. These are expressed by nociceptive neurons. They are located at the free nerve endings

of the C fibers.

2) There is a wide variety of TRP channels, which mediate different sensations (temperatures and

chemicals).

a. TRP1 responds to cold, TRPV2 responds to hot.

b. Some also respond to chemicals.

3) Determined by seeing the best response of the channel through whole-cell recording and

changing temperatures.

Pain Pathway:

1) Synapse onto projection neurons (substantia gelatinosa, SG). These neurons cross to the other

side of the spinal cord (desucces) and then go straight up to the brain through thalamus.

2) This pathway for pain is different and is called the spinothalamic pathway.

a. After synapsing with the SG neurons (projection neurons), the axon goes straight up to

the thalamus.

Pathway for Mechanosensory vs. Pain:

1) Mechanosensory/Dorsal Column-Medial Lemniscal: Hits receptor DRG birfurcates

one axon goes through the dorsal column lemniscal pathway after it decussates in

medulla.

2) Pain/Antereolateral: C fibers from nociceptor go through a different DRG cell and synapse

onto a projection neuron (substantia gelatinosa) in the dorsal horn. This then

decussates and goes up the antereolateral pathway.

3) Note: See that mechanosensory input decussates at the medulla. In contrast, pain inputs

decussate in the dorsal spinal cord.

Gate Theory of Pain:

+ means excitatory, - means inhibitory.

1) Two different receptors: one mediates pain, another mediates mechanostimulation.

2) C fiber (pain) synapses with the projection neuron.

3) C fibers also innervate an inhibitory neuron.

4) Follow the red pathway for C pain fibers.

a. C fibers synapse and excite the pain projection neuron (more pain).

b. But, we can also cause pain by inhibiting the inhibitory interneuron (double negative, so

it excites the pain neuron).

5) There are also inputs from the regular mechanosensory axons which synapse onto inhibitory

interneurons and projection neurons.

a. Can excite projection neuron. This happens when we stimulate the skin a lot, causing

pain.

b. “Rubbing to Decrease Pain:” Can also excite the black interneuron to inhibit the pain

projection neuron. This causes less pain.

6) The Gate Theory: Projection (pain) neurons receive mechanosensory and nociceptor

information.

a. Inhibitory neurons inverts signal, giving us the “rubbing to decrease” phenomena.

7) A high frequency of stimulation to the mechanoreceptor can cause pain. There is a greater

“factor” of stimulation to the pain projection neuron vs. the inhibitory interneuron. So, we can

cause pain if we rub something too hard.

Control of Pain:

1) There are two pathways for the control of pain.

a. Red Line: Natural opioids release and activate serotonin, inhibiting nociceptive neurons

(decrease pain).

Summary of both pathways.

This is a cross section of the SPINAL CORD before we reach the medulla.

1) Medial Lemniscus (Top): Crosses the midline in the medulla. The somatotopic

representation gets inverted.

a. Displays head medially, sacrum laterally, hands and feet ventrally.

2) Spinothalamic Pathway/Pain: Cross in spinal cord.

a. Fibers originating in lumbar and sacral are located laterally, while those from

the cervical spine (C) are positioned medially.

3) Since the somatosensory pathway doesn’t cross until the brain (medulla) and the pain

pathway crosses in the spinal cord itself, we get inversion.

4/9: Visual System Nice powerpoint follow along

http://www.ic.ucsc.edu/~bruceb/psyc123/Vision123.html.pdf

Basic Anatomy

General Anatomy of Retina:

1) Thin black layer shown is the pigmented epithelium.

a. Functions to 1) absorb light of extra light bouncing around retina 2)

regenerates/maintain photoreceptors.

2) Retina composed of a thin sheet of neurons. They and the optic nerve are part of the CNS.

3) At the fovea, neurons are shifted aside so light goes directly to the photoreceptors.

a. Many photoreceptors are packed in the fovea. These are all composed of cone

photoreceptors, designed to see things with high accuracy.

1) Light goes through layers of cells before it impinges on photoreceptors.

a. Cells are pushed aside at the fovea, though (not shown here).

2) RPE composes the outer layer and we move inwardly from there.

3) Outer nuclear layer: Contains the nuclei of the photoreceptor cells.

a. These cells transduce the signals – signals sent the opposite direction that the

light is coming in.

4) Inner Nuclear Layer: photoreceptors synapse onto bipolar cells.

a. Bipolar because they spread in two different directions.

b. This layer also contains horizontal and amacrine cells which summate

convergent signals (will talk about in detail later).

5) Not all of these cells fire action potentials.

a. The only cells that spike are the ganglion layer cells (output cells to the optic

nerve and cortex).

b. We need a spiking output at the top. The different types of lower cells merely

mediate the different types of the light that comes in.

1) Light impinges on the photoreceptive pigments at the bottom, then sensory information

goes back up.

1) Photoreceptors are on top.

2) Outer nuclear layer has the cell bodies of the photoreceptors.

3) Inner nuclear layer contains cell bodies of horizontal cells and amacrine cells.

4) Ganglion layer sends out information to the optic nerve.

5) Conduction in visual system is slow because we go through both second messenger

pathway and several synapses before even hitting the CNS.

6) The different types of bipolar cells extract specific types of information from visual field.

7) Rods and cones synapse in different locations in the retina.

1) The blind spot is located where the optic nerve comes in (NOT the place the light is

pointing right now).

2) All the axons in the retina have to go to the optic nerve to get into the CNS.

a. There are no receptors over the optic nerve, so we have a blind spot.

1) Recall the fovea, the point of sharpest focus. The density of photoreceptors, bipolar cells,

and ganglion cells is highest here.

2) Fovea/Cones: In the fovea, there is a 1:1 relationship between cone: bipolar cell, meaning

we have much higher acuity (vision is sharpest). Information about the object is

preserved or even enhanced.

3) Periphery/Rods: As we move away from the fovea, we get more convergence. If many

photoreceptors converge into one bipolar cell, we have lower acuity. This is because more

convergence means pixels get bigger, less fine.

a. Also amplifies signal as well by adding together activity from many photoreceptors.

b. See in the dark, but acuity is not as good, though.

4) Note the relative amount of cones vs. rodes in the fovea - fovea basically made of all cones.

Types of Photoreceptors:

1) Split into rods and cones.

2) The cone has a higher membrane capacitance because there’s more surface area due to

folds.

3) Outer segments contain the photoreceptors.

Biochemistry of Retinal:

1) Rhodopsin is the visual pigment in rod cells. It is made of a protein component and light-

absorbing component.

a. Protein component: Opsin.

b. Light-Absorbing Component: Retinal.

2) Opsin, the protein, wraps seven times across the membrane of the rod.

3) Retinal absorbs light changes conformation (11-cis all-trans) expanding and allowing the

protein on the membrane to uncoil. This activates second messenger system.

Detailing the Transduction Pathway

1) This stuff was worked out in rods because there is a high density of pigments there.

2) In the dark, we have cGMP gated channels open because cGMP is high, allowing Na+ and

Ca2+ to come in the cell.

a. Steady influx of Na+ maintains cell at depolarized -40 mV.

i. Result: Constant release of glutamate

3) In the light, rhodopsin is excited by absorption of photons, activating transducin

activate phosphodiesterase dropping cGMP levels closing cGMP-gated channels.

a. The alpha and beta components of transducin (T) separate. The alpha component

activates PDE. PDE breaks down cGMP into GMP. Since cGMP levels are lower, the

channels close, hyperpolarizing the cell.

b. cGMP channels are dependent on cGMP. The more cGMP we have, the more

channels open.

c. In this scenario in the light, less Ca and Na come into the cell, hyperpolarizing the

cell.

4/11: Visual System Continued

1) All of this transduction is happening in the outer segment.

2) When the cGMP channels open and we depolarize the cell, we release glutamate.

3) Dark: Since the channels are open, we are depolarized. Glutamate is released at high

concentrations.

4) Light: Channels close, hyperpolarization, less glutamate release

a. Figure C: More light intensity = more hyperpolarization because more channels

close.

In RODS!

1) Note all the amplification that occurs after one photon of light is absorbed by rhodopsin!

2) One photon thus affects membrane potential quite a bit, sending a signal to the brain that

light is in the visual field.

3) This is not a rapid response compared to mechanoreceptors because it has to go through

this long pathway!

1) This is the reason why it’s very hard seeing longer wavelengths in the dark (like red).

Rhodopsin can’t pick up those wavelengths.

2) Notice the correlation between the wavelengths for human perception vs. what rhodopsin

absorbs.

a. Proves that we’re basically using rods in the dark because no cones are involved

here.

1) Since there is processing already in the retina, unlike the mechanoreceptors, the receptive

field is defined differently.

2) There is a donut of cells surrounding the pinkish photoreceptors in the middle. These

surrounding cells are also able to change activity when they synapse to the same bipolar cell.

3) We essentially get a larger receptive field produced as we move “further down” the pathway of

transduction.

i. This is because we have convergence of rods onto bipolar/ganglion cells, “summing”

their receptive fields as we move downstream.

4) Fovea vs. periphery (top part of figure):

d. Fovea has much smaller (blue dots) receptive fields because fovea has mainly

cones, which are 1:1 ratio between cones and bipolar.

e. Convergence of photoreceptors in the periphery, little in the fovea.

Bipolar Cells:

1) Function: Receive input from photoreceptors.

2) Note that the axons/synapses land in different layers (off vs. on plexiform layers),

meaning they have different functions as well.

What do mean by off vs. on?

1) Bipolar cells are the pathway from photoreceptors to ganglion cells.

a. Sign is conserved between the bipolar and ganglion cell.

b. Ganglion cells are the ones that actually fire.

2) Divergence: Cone synapses onto many bipolar cells.

a. Function: Allows for parallel processing.

b. Note that one bipolar cell is off-center, another is on-center.

Concept of On vs. Off Center:

1) We examine the output response from these neurons.

2) Off-Center: Depolarization in the dark.

a. Dark: Opposite of what’s shown in the figure. Glutamate is released from the cone

cell and activates ionotropic AMPA receptors, causing depolarization.

i. Same thing happens in the next step to the ganglion cells. This means we

have a constitutive inward current (depolarization).

b. Light: Opposite as in the dark. We remove the constitutive inward current,

hyperpolarization meaning less glutamate is released. The ganglion fires less.

This is what we mean by off. When we shine light on these cells, they stop firing.

3) On-Center: Fires in response to light.

a. These cells express a different metabotropic glutamate receptor.

b. Dark: When glutamate is released, we actually hyperpolarize the cell by opening

K channels.

i. So, we decrease firing rates in the dark.

c. Light: Opposite. We depolarize by closing K channels. More glutamate is released

because of the depolarization, increasing firing rate of ganglion cells.

The last point shows the significance of the parallel processing.

Within the receptive field, we can distinguish between center and surround regions, where light causes

opposite responses. The surround region is antagonistic to the center region.

1) In the indirect pathway, we factor in the horizontal cells.

a. This indirect pathway is termed the center surround. It uses GABA (see next

slide).

2) We have overlapping receptive fields – we can consider each receptor as both a center

and surround.

3) Center and surround are always antagonistic to one another. The light in the surround

hyperpolarizes and thus antagonizes.

1) Horizontal cells (H) release GABA and inhibit.

2) On the left side, GABA release is constitutive from the horizontal cell.

3) When we shine light on the direct, off-center pathway cone (C), C hyperpolarizes less

glutamate is released bipolar cell (B) hyperpolarizes.

1) Light to the surround.

2) When we shine light on the surround, we have hyperpolarization less glutamate is

released from the left cell. This means less GABA is released by the horizontal cell (less

constitutive hyperpolarizing current).

a. Less inhibition means more depolarization at cell C and more glutamate released

at C, meaning depolarization in the bipolar cell (B).

3) This is antagonistic to what happened when the center itself was illuminated.

a. See last slide. It hyperpolarized vs. now it’s depolarized.

For ON-Cell, we still have antagonistic relationship:

1) Stimulus Pattern: Type of light stimulating the retina. Each column shows response for

OFF or ON cell.

2) RG Firing Rate: We record retinal ganglion cells firing rate in response to light. Notice that

some cells are sustained (tonic) vs. phasic (transient).

3) Main Takeaway: The surround is always antagonist to whatever the center is doing.

4) On Center Cell: Shine light on center increase in firing with more glutamate

released/depolarization.

a. Surround Only: decrease in firing (antagonistic).

b. Highest Rate of Firing/Best Response: Shine light in center but no light in

surround.

5) Reversed for OFF cell.

a. Best Response/Maximal Firing Rate: Excited by dark spot in center and light in

surround.

6) We have parallel processing because light is seen by both an ON and OFF cell circuit and

PHASIC and TONIC receptors.

1) Broad light (3) increase in response compared to baseline. This is because the response

in the center is always greater than the response in the surround.

2) Maximal firing rate in the bottom.

3) We also can really easily detect changes in light when we move from center to surround

because the firing pattern changes a LOT.

a. For example, the response of a given cell to light will be stronger if the light

portion of the visual field is adjacent to a dark portion. As a result, the retinal

mechanisms for contrast enhancement make our visual systems very sensitive to

edges or borders and allow us to perceive even weak contrasts

4/14: Visual System 3

1) Off cell: Center and surround illuminated,

a. Dark middle leads to increased firing.

b. All Dark: Kind of faster than nothing because center response is stronger than

surround.

1) Step Function: Moving from full light to full dark is a step function.

2) Curve Function: When we have a shadow moving across the receptive field, we are no

longer a step function.

a. B: Only cover annulus, so low rate of (antagonistic) firing.

b. C: Shadow covers middle and side leads to increased firing (center is stronger

response).

c. D: Cover all (more surround) leads to decreased firing.

3) In the curve function, we exaggerate where the edge hits, leading to an over and

undershoot.

a. Perceive huge decreases and increases as the shadow moves into the receptive field.

b. This exaggerates the edges – sharp objects (trees, shadows above you

(predator). Emphasis of contrast by the horizontal cells (center vs. surround).

Emphasis of Moving Objects

1) Bars of Light: On Cell

a. Reduce firing before white bar moves through the surround, increase a

lot, and decrease after it goes by.

b. Broader bar = broader peak because we illuminate center and surround

at the same time.

c. Shows exactly how wide the thing is that’s crossing our vision.

2) Parallel Processing: At the same time we have an OFF cell transmitting

complementary information better perception of image because both bright

and dark edges are accounted for.

3) Bright edges and dark edges are signaled by sharp changes in firing.

4) Moving objects object elicits strong firing in the ganglion cell population near

the edges of the object’s image because these are the only regions of spatial

contrast and the only regions where the light intensity changes over time.

Color Vision:

1) The L, M, and S cones are combined together gives us the spectrum of red vs. green, blue vs.

yellow.

a. Note: We don’t actually have yellow “on” blue “off” – we get it through a subtraction

process.

Subtypes of Retinal Ganglion Cells:

Output of Retina and Where it goes:

1) There are many types of ganglion cells mediating different types of light stimuli.

2) M-Type vs. P-Type:

a. M: Bigger cell bodies and axons, quick transmission.

i. Function: Movement in the visual field, transient responses.

b. P: Smaller axons, slower transmission, sustained response,

i. Function: color and texture (output of the color system). These are all in the

retina.

c. Axons of M and P type axons go to the optic nerve.

4/15: Visual Processing.

1) Temporal vs. Nasal Retinal Ganglion Cells:

a. Temporal: Side portion, like the right half of the right eye.

b. Nasal: Nearer to the nose.

1) At the optic chiasm, the retinal ganglion cells cross to the other side of the brain.

2) Binocular Vision:

a. Differs from the frog vision. In frog vision, all the information in the right eye crosses

and goes to the left side of the brain.

b. In binocular vision, each eye is represented on both halves of the brain.

3) Blue Lines: From the right eye, the left side (nasal side) of the right retina crosses the chiasm

and goes to the opposite side of the brain.

a. From the left eye, the left side of the left eye (temporal) stays on the same side of the

brain.

b. So, we can see that both the left and right eyes send their axons to the left side of the

brain (follow blue lines).

4) Opposite for the red lines.

5) We send all these inputs into the lateral geniculate nucleus (thalamus).

1) Follow the red axons. The axons from the temporal part of left eye stay on the same side of

the brain, while the nasal axons from the right eye must cross over to the left side of the

brain.

Pattern: Nasal crosses over, Temporal stays the same.

Consequences of Visual Field Deficits:

See I … I see, I see! (contra, ipslateral, ipslateral, contra, ips, contra)

1) The LGN has six layers, segregated by eye.

a. The axons from the ganglion cells in the retina must, in development, go to these

specific layers of the LGN.

b. Thus, we setup the x-y visual field by mapping this x-y visual field onto the LGN and

cortex.

2) Left Eye: The right LGN receives inputs in layers 1,4, and 6 from this contralateral left eye

through the yellow lines,

3) Right Eye: The right LGN receives inputs in layers 2,3, and 5 from the ipslateral right eye.

4) So, both eyes receive the same type of information, but inputs are segregated in the LGN by

eye.

5) Layers 1 and 2 detect motion.

a. Receive input from M-type ganglion cells (concerned with movement).

b. Land on layers 1 (contralateral) and 2 (ipslateral) viewing the same point in space.

6) Layers 3,4,5,6 very important for detecting color and texture

a. Accept input from P-type ganglion cells (smaller, for color)

LGN to Cortex (right side of diagram):

1) Layer 4 is still major input in the cortex.

2) Magnocellular channel (1,2 from LGN) serves the M cells (movement, larger) and Parvocellular

channel serves the P cells (color and texture, 3-6 from LGN).

3) All the LGN axons go to the V1 visual cortex through optic radiation (not bundled). They each go

to the cortex on their own.

4) Continual Segregation (Retinotopic Map): we saw segregation of eyes in the LGN with different

input layers. They are still separated in the cortex. For example, axons concerned with

movement (M type) versus color (P-type) land in different parts of layer IV of cortex.

a. M-Type: If we examine the two axons coding for movement (1 and 2), we see that they

represent the same point in space, but land in different places in the cortex. I.E.,

contralateral and ipslateral inputs are segregated in the cortex.

The LGN: Stain that shows cell bodies; notice that axons go to only layers 1,4, and 6 for one

eye and 2,3, and 5 for the other eye.

1) Retinotopic Map: Visual field is found on retina (x,y position), x-y mapping is maintained in LGN

(previous slide) and maintained in the visual cortex (blue and red axons land in distinct places in

the cortex).

A) Closer to fovea receptive field small compared to periphery (periphery has

lots of convergence).

B) Cortex dedicates a lot of space to the fovea. The fovea takes up a small area,

but is packed with cone photoceptors (1:1 ratio photoreceptor to bipolar cell)

and thus takes up almost 50% of the cortex.

C) By doing this, we get amplification of the parts of visual field that we want to

see.

4/16: Final Day of Visual, Start Auditory:

V1 Cortex:

1) Layers of the V1 cortex.

2) Note that the synaptic inputs from the M and P cells go primarily to layer IV (as in the

somatosensory).

1) The same point in space is seen by M cells, (Layer 4, C alpha) and P cells (Layer IV, C beta).

2) Stellate cells then transmit this information to other parts of the cortex.

3) Continual Segregation: There are still eye-specific patches in the cortex until layers 2,3. This is

where we finally get convergence of stellate cells.

Note that V1 is a lot darker/stronger because that’s where all the inputs from the LGN came in.

1) Lose x-y mapping moving from V1 and V2 parts of the cortex. Processed in the association

cortex (V2).

1) Neurons project from LGN through optic radiation to the V1 cortex – they don’t travel in tight

nerves on this pathway.

2) X-Y fields from LGN are maintained and mapped retinotopically to the V1.

a. Shown in zoom in of layer four. The grey from left eye, white from the right eye in the

cortex (V1) is maintained.

See how the colors stay in specific areas of the cortex – retinotopic map idea again.

Input from left and right eye:

- Radioactive signal – labeled eye is where white is.

- Some particular point in x-y space is represented by the unlabeled and labelled in layer 4.

- Note the convergence after layer IV – some cells get mixed inputs (start getting binocularity)

after going past layer IV.

1) In visual cortex, neurons respond selectively to bars/lines of different orientations. This comes

from alignment of many LGN center-surround receptive fields.

2) Layer IVC-Beta: Center surround responses in IVCbeta. Each cell represents a point in space.

3) Layer III (Beta): After convergence (projection neuron) in IIIbeta, we get a bar of center-

surround.

4) This “bar” of center-surround responds to specific orientations – the middle orientation.

a. There’s lots of cell nearby that responds best to different angles of light.

1) Each spot in layer 2-3 will have a cell that responds best to a specific angle of light.

1) These columns consist of cells with similar functional properties.

2) Ocular Dominance: Relative strength of input from each eye.

a. Alternating Bands: Shows the segregation of left-eye and right-eye in layer IV getting

inputs from LGN.

3) Blobs: Groups of color-selective neurons – information about surfaces.

4/16 and 4/18 - Auditory System:

1) The outside of the ear captures sound waves and transmits it down the ear canal (meatus) to

the sensory complex.

2) Inside the cochlea, there are axons that go to the cochlear nerve.

1) As sound waves come in, the stapes drives deeper into the oval window (piston-like).

2) Stapes pushes on oval window and transduces sound through pressure changes.

a. The changes in pressure are propagated through the liquid medium (scala vestibule).

1) Mechanically sensitive hair bundles protrude in the liquid inside scala media.

2) Motion in the tectorial membrane is detected by these hair cells

Organ of corti zoomed in.

1) Outer hair cells: Involved in amplification by changing length during basilar membrane

movement.

a. These hair cells are embedded in tectorial membrane.

2) Inner hair cells: Function is to sense frequency of sound waves.

a. Not embedded in tectorial; respond to fluid changes.

3) Afferent neurons go to the CNS.

4) Movement of tectorial and basilar membrane is detected by the hair cells.

1) Characteristics of the solution in the scala media.

a. Inner hair cells are in contact with the endolymph.

b. Epithelial cells generate high K concentration inside the endolymph.

2) The high K concentrations depolarize the hair cells.

1) The stereocilia attach on the top of the hair cell.

2) Hair cell is in the epithelia.

3) Cilia on top exposed to high K endolymph and the rest of cell (below) is at normal cellular

concentration of K+.

1) The cilia are structurally attached to the hair and pivot in the membrane.

2) Cell membrane actually covers the hair cells, making it possible to transduce through the hairs.

3) Takes very small amount of movement to respond to the fluid. Recall that the movement of the

two membranes (tectorial and basal) causes the fluid shift to push against the cilia. This causes

a voltage response.

1) Note that there are attachments between the longer and shorter cilia.

2) Side links cause cilia to bend together.

3) After force is applied, the cilia, linked together with tip links, mechanically stretch and open

potassium channels.

4) These channels transduce mechanical to electrical energy:

a. In a normal hair cell, there are about 15% of these resting potassium channels open.

b. Thus, we get potassium entering cell to cause depolarization. Resting channel is set by

this influx of ions.

1) Positive voltage outside pushes the K+ inward.

1) Displacement toward tall edge opens additional channels depolarization.

2) Displacement toward short edge closes channels open at rest hyperpolarization.

3) This all occurs because of the tip link. One move, they all move together.

4) Membrane potential oscillates as we push and pull.

5) I-V relationship:

a. Lot more response when you go +200 nm vs. -200 nm.

Rectifying curve: Property that causes current to flow more readily in one direction than another. In this

case, this is caused by two things:

Two Reasons for Rectifying Curve:

Mechanical: Quickly close all the 15% of channels that were open at rest, whereas we have a decent saturation curve on the right hand side. Electrical: Hard to let K+ out against its concentration/voltage gradient and hyperpolarize the cell when moving toward the short end of cilia.

b. Past 100 nm deflection all channels open, past “operating range.” Saturated.

Stretched cochlea.

1) Stapes at oval window transduce sound by changing pressure propagating through liquid of

scala vestibuli, basilar membrane moves in response.

2) Figure C: Mechanical Operation of Basilar Membrane: basal membrane moves in response to

pressure through the oval window.

3) Figure D: Shows what really happens. Basilar membrane varies in mechanical properties. We

have differential best responses based on where we are on the membrane.

a. Apex: Thin and floppy. Responds best to low frequency.

b. Base: narrow, stiff. Responds best to high frequency.

c. Between the 20 Khz and 20 Hz, the basiliar membrane can respond best at different

positions due to properties of basiliar membrane itself.

1) Differential Best Frequency: Each wave generated reaches its max amplitude at a particular

position appropriate for the frequency of the wave, then declines in size as it goes to the apex.

a. Analogy of a wave going to shore. Max at a point, then breaks and rapidly fades.

2) Tonotopic Map: Specific arrangement of frequency-position

a. Each component of the complex sound wave establishes a wave that has its own best

frequency response at a certain position on the basilar membrane.

b. Basilar membrane is thus a mechanical frequency analyzer.

3) Example - 10K Hz: Hair cells on that part of membrane respond, membrane moves and the hair

cells depolarize rapidly too.

1) Reminder: Low frequency/apex, high frequency/base.

2) Cell A: Large, slow depolarization and hyperpolarization.

a. Best Response is thus for slow frequencies (matches up).

3) Cell B: Best at high frequencies. Its depolarization and hyperpolarization is fast, so it can’t really

match with the low frequency waves too well.

a. Cell A doesn’t respond as well, though.

4) So what? This is where we start encoding stimulus frequencies and intensities!

1) Transduction of Signal: Hair cells depolarize through ion channels.

a. Depolarization through K+ V-Ca channels open, Ca comes in (continual

depolarization) Ca-K channels open (K+ outward, hyperpolarize) Ca also is

pumped out reset.

1) There are different transcripts of Ca-K channels in hair cells

a. Function: Responds to different frequencies.

2) Low Frequency Best Response:

a. Ca-K channel opens and closes very slowly.

3) High Frequency Best Response:

a. Different transcript (mRNA) of Ca-K channel – closes very rapidly.

4) Principle: Rate of going Ca-K open/closing governs how fast the cell can go through one cycle.

a. If we repolarize faster, we can accommodate new movement to generate a new cycle.

b. Differential distribution of Ca-K channels dictates whether cell can respond best to low

or high frequencies.

Antibiotics can kill hair cells! Goes through the ion channels in hair cells.

1) Outer hair cells amplify the cochlear effect.

1) Auditory system is tonotopically mapped by frequency.

2) The information from one side decussates and actually goes up both sides of the CNS

3) At second synapse we’re already getting comparison of two sides of the auditory system

(the inputs)