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reversal potential
also known as the nernst potential

the driving force of an ion through a channel essentially

I=G(V-E)

I is current-can be meausured using a voltage clamp

V=voltage across membrane...meausred microelectrodes

E=-60/z *log(ion in/ion out conc)
PSC
postsynaptic current
PSP
postsynaptic potential

on postsynaptic cell

graded potentials
EPP
macroscopic current resulting from the summed opening of many ion channels

end plate is always summed value of many channels
EPSP
excitatory post synaptic potential
IPSP
inhibitory post synaptic potential
What determines postsynaptic excitation and inhibition?

draw a picture
1)nernst potential
...if more positive than threshold, will be excitatory
...if less positive, will be inhibitory

glutamat channels are non-selective cation

GABA channels are chloride inhibitory
what contains graded potentials?

what contains action potentials?
graded: dendrites contain NT-gated channels

action: cell body + axon contains voltage-dependent channels
draw an example of summation
draw the summation pathway
NT gated channels also called what?

talk about these
ionotropic

NT-gated channels are also called “ionotropic” neurotransmitter receptors.

Ionotropic receptors allow a NT to very rapidly change the membrane potential of the dendrites and cell body of postsynaptic cell, altering
the frequency of a.p.’s

In addition, if the NT-gated ionotropic receptor is permeable to calcium ions, these will diffuse into the postsynaptic cell and may stimulate enzymes and alter protein function or expression, acting as messenger molecules

Ionotropic NT receptors are complex molecules – Made of several large subunits.

The “nicotinic” Ach receptor at the neuromuscular junction has a relatively simple gating function – Only Ach required.
draw ionotropic receptor
ligand gated receptors
draw acetycholine metabolism in cholinergic nerve terminals

what kind of receptor is this?
ionotropic
draw glutamate synthesis cycle
what are two examples of extremely simple receptors?
nicotinic ACh receptor
and the Glutamate AMPA receptor
talk about the NMDA receptor

p
-depolarization forces Mg ion out of the channel and unblocks it....hyperpolarization blocks channel

if the cell is not previosly depolarized, there will be no response to glutamate
N
Magnesium
Depolarized
And........glycine
draw the EPSC projection of a NMDA channel
So, even if a synapse that releases glutamate is active, NMDA receptors will only be fully open if the cell is previously depolarized and the Mg block is therefore removed.

The NMDA receptor therefore creates a glutaminergic synapse that is only effective if the postsynaptic cell has been recently activated AND IS STILL DEPOLARIZED by another synapse

– a mechanism useful for creating an association between two synaptic inputs to a neuron

Involved in learning and memory at the cellular level
what is interesting about a single NT such as glutamate?
can act on a diverse population of receptors to create postsynaptic potential with different characteristics and functions
2 inhibitory neurotransmitters
GABA and Glycine
synthesis and release of GABA
VIATT: vesicular inhibitory amino acid transporter
draw a membrane potential scheme of GABA inhibition
stimulation of presynaptic GABAergic interneuron
third of the synapses in the braine use what inhibitory neurotransmitter?
GABA
GABAa and GABAb...which one is ionotropic and which one is metabotropic?
ionotropic: GABAa
metabotropic: GABAb
Draw the GABA receptor
only gaba is needed to activate...all of the other subunits change the receptor in some manner

there are actually 2 sites for GABA to bind
Gabby did drugs
are ionotropic NT receptors complex simple or complex proteins?
complex....multiple spanning subunit and usually more than one binding site for the NT
draw the nACh membrane spanning receptor
most important receptor in brain function
glutamate
describe architecture of ligand-gated receptors

p
basics of metabotropic NT receptors
Metabotropic NT receptors

Gpro couples

Initiate production of second messengers and acrivation of remote ion channels

Act via GTP-binding proteins

Potential for enormous signal amplification

Slow response time
very basic of G pro coupled receptor and posible response
types of gtp-binding protein

p

2 types
draw amplification scheme
besides altering membrane potentials in postsynaptic cells, what else can NT's do?
In addition to altering the membrane potential of postsynaptic cells, by opening ion channels, NT’s can act to regulate the long-term activity of the postsynaptic cell.

This regulation can occur through the regulation of gene expression by a variety of possible pathways….
All of the classic second messenger pathways are available to NT’s via:
activation of metabotropic receptors

Activation of calcium-permeable ionotropic receptors leading to increased postsynaptic cellular calcium ion concentration.
Talk about CREB

p
Phosphorylation of CREB allows it to bind co-activators:not shown.

This stimulates RNA polymerase to begin synthesis of RNA
diagram and talk about long-term synaptic depression
Activation of protein kinases by second messengers can also lead to phosphorylation of target proteins in the postsynaptic cell and medium-term changes in postsynaptic cell function.

These changes in function are often targeted towards proteins that regulate the sensitivity of the synapse to further stimulation by NT’s

Thus stimulation of a synapse leads via this feedback to long term changes in the sensitivity of that synapse – a form of “learning”.

For instance prolonged activity at synapses made with cerebellar neurons leads to a long-term reduction in the sensitivity of the post-synaptic receptors to NT’s – “long-term synaptic depression”.
what does a cerebellar purkinje cell look like?
what can alter long-term strenght of pre-synaptic terminal?
Calcium influx into the presynaptic terminal during prolonged stimulation can also result in protein phosphorylation and long-term changes in synaptic strength.

E.g. stimulation of tyrosine hydroxylase – an enzyme needed for biogenic amine synthesis.

In this case, prior activity at the synapse results in an increase in long term synaptic strength – more amine NT is produced.
plasticity basics
So chemical synapses allow both direct, immediate transmission of information via changes in membrane potential…..

Regulation of postsynaptic action potential frequency

and more subtle, long-term regulation….

through intracellular messenger pathways, the synapses are rendered “plastic” – the strength of the connection depends on the amount of prior activity at a synapse.

Plasticity is the building-block of learning and memory.
draw a scheme of peptide neurotransmitter processing
Pre-propeptide occurs in RER

Propeptide occurs in Golgi
3 peptide categories with examples and types of amino acid properties
talk about opioid family of peptide NT's
Leu-Enkephalin, the dynorphins and the endorphins are members of the opioid family of peptide NT’s

They bind to the same postsynaptic receptor proteins that bind opium (morphine) and synthetic opiates (fentanyl)

Opioid peptides are widely distributed in the presynaptic terminals of neurons throughout the brain – often co-localized with small-molecule NT’s like GABA or 5H-T

When injected into the brain opioid peptide NT’s act as analgesics and depressants

Opioid peptide generally act through G-protein linked receptors, not ionotropic receptors

-amplified long term effects on postsynaptic cell metabolism and function
2 unconventional NT's
Endocannabinoids
Gases – NO (nitric oxide)
marijuana plant name
Cannabis sativa
active component of marijuana
THC

tetrahydrocannabinol
areas of the brain that marijuana affects
1)Substantia nigra
2)Caudate putamen
3)Hippocampus
4)Cerebellum
Endo-cannabinoids
Endo-cannabinoids

- bind to cannabinoid receptor proteins – the proteins that bind THC, the active ingredient of marijuana

They are fatty acids with polar head groups

Produced in the cells by enzymes that are activated by Ca2+. Diffuse through membrane onto target cell

Participate in synaptic regulation, rather than actual transmission.

E.g. retrograde inhibition of inhibitory synapses in the cerebellum and hippocampus

-one of their main functions is to regulate the release of GABA at inhibitory terminals
retrograde signalling
In neuroscience, retrograde signaling is a phenomenon in which a signal travels from a postsynaptic neuron to a presynaptic one. Endocannabinoids are known to play a role in retrograde signaling, with the molecules being synthesized postsynaptically and acting presynaptically. Retrograde signaling may also play a role in long-term potentiation, a proposed mechanism of learning and memory, although this is controversial
GABA function
In vertebrates, GABA acts at inhibitory synapses in the brain by binding to specific transmembrane receptors in the plasma membrane of both pre- and postsynaptic neuronal processes. This binding causes the opening of ion channels to allow the flow of either negatively charged chloride ions into the cell or positively charged potassium ions out of the cell. This action results in a negative change in the transmembrane potential, usually causing hyperpolarization
talk about endocannibinoid-mediated retrograde control of GABA release
-depolarization of the postsynaptic neuron causes increases in calcium levels
-increased calcium levels cause synthesis and release of endocannabinoids
-retrograded from post synaptic cell to pre synaptic cell
-Bind to CB1 receptors and inhibit the amount of GABA released when pre-synaptic cells have AP's
talk about NO and its effects
Produced by a Ca2+ - activated enzyme, NO-synthase, present in some neurons and other cells
Diffuses across to other neurons to stimulate enzymes produce the messenger cGMP in the “postsynaptic” cell
Well-known role in inducing muscle relaxation
somatosensation
Somatosensation is a sensory modality that covers

Touch and vibration

Pain , temperature (considered by some to be separate)

Proprioception - information from joint and muscle receptors – used to control muscle movement, not perceived

Mechanosensory information from receptor cells in the viscera
ganglion
collection of neuronal cell bodies outside of the CNS
medulla oblongata
The medulla oblongata is the lower portion of the brainstem. It deals with autonomic functions, such as breathing and blood pressure. The cardiac center is the part of the medulla oblongata responsible for controlling the heart rate.
dorsal root ganglion
little notches of ganglions off of spinal cord
preganglion fibers
originate in the brain or spinal cord
describe the path of mechanosensation and also to a lesser degree of pain
Machanosensation begins with a mechanosensory receptor neuron.

This neuron typically has:
Its cell body in the dorsal root ganglion of the spinal cord.
Its dendrites in layers of the skin (or viscera)
An axon that travels up the spinal cord to make excitatatory synaptic contact with “second order” neurons in the medulla

The second order mechanosensory cell, with dendrites and cell body in the cuneate or gracile nucleus of the medulla, sends an axon that terminates in the ventral posterior nuclear complex of the thalamus, making an excitatory synaptic connection with a “third order” neuron.

The third order mechanosensory cell, with dendrites and cell body in the VPN thalamus, sends an axon that terminates in the post-central gyrus of the cerebral cortex, making contact with cerebral neurons.

Thus the post central gyrus is the somosensory area of the cerebral cortex.

Pain and temperature info. travels by a slightly different pathway to the somatosensory cortex

ipsalateral side is the side that the nerve enters on....contralateral side is the oposite side
dorsal
backside of spine, top part of brain
ventral
front side of spine, lower part of brain
Rostral
toward front of brain or toward the head
caudal
toward the feet or toward the rear of the brain
superior
straight up
inferior
straight down
posterior
backwards
anterior
forward
describe mechanotransduction

10/16 pictures if needed

long explanation required
The transmission of sensory information begins with the transduction of a mechanical stimulus at the skin into an increase in the frequency of action potentials traveling through the mechanosensory neuron

The plasma membrane of the dendrites contain mechanosensitive channels, mostly permeable to sodium
ions.

Mechanotransduction begins when the dendrites of the mechanosensory neuron, under the skin, are distorted by a mechanical stimulus.

This stresses the cell membrane and opens mechanosensitive channels – which are cation non-selective.

Sodium ions flow through the channels and depolarize the dendrites of the mechanosensitive neuron

The resulting depolarization is called the “generator” or “receptor” potential. It is a graded {passive} potential which increases in amplitude with stimulus strength as more channels open). It is similar in its nature to the EPP or PSP

If the stimulus is strong enough, the generator potential will grow to exceed threshold and an action potential will be produced.

The action potential will propagate down the axon to the spinal cord and beyond.

If the stimulus is maintained, a train of action potentials will be generated in the mechanosensory neuron.

The frequency of action potentials in the train will be proportional to the stimulus strength – up to a maximum frequency, when the neuron “saturates”.

Thus information about stimulus strength is encoded in terms of the frequency of action potentials,

Between threshold and saturation lies a dynamic range – a range of stimulus strength within which the a.p. potential activity within a neuron reflects stimulus strength.

The action potential travels down the axon, the generator potential,
Being passive, does not spread far down the axon. So only the
Action potential arrives at the spinal cord
draw action potential frequency saturation curve
all neurons have spontaneeous background

spontaneous background is the flat part of the curve

Spontaneous background is random
what is an important feature that varies from one mechanosensory neuron to another?
An important feature that varies from one mechanosensory neuron to another is the degree to which the neuron’s response tracks sustained stimulation.

For some mechanosensory neurons, the a.p. frequency drops off during prolonged stimulation – the neuron “adapts”. This means that the neuron responds best to phasic, or rapidly changing stimuli and not to steady stimuli.

Other neurons respond steadily to prolonged stimulation – their response is said to be “tonic”

Adaptation represents an important early step in processing sensory information – it tunes some receptors to rapidly changing, high frequency stimuli like vibration and it reduces the impact of unchanging signals that are of less “interest”.

Something that wants to detect vibrations is said to be phasic
talk about skin mechanoreceptors
Meissner corpuscle: Touch Phasic

Pacinian Corpuscle: Vibration Phasic

Ruffini's Corpuscles: Stretching Tonic

Merkel's disks: Touch Pressure tonic

Free Nerve endings: pain, temp, crude touch tonic, hig threshold
what are 2 proprioceptrive sensory structures and describe them
muscle spindle and golgi tendon organ

muscle spindle: detects muscle length and initiates the stretch reflex

golgi tendon organ: receptor that detects tension in tendon

Axons from proprioceptive sensory structures in muscles, joints and tendons send branches via the dorsal root ganglion to the spinal cord and to the medulla (and thence to the thalamus and the somatosensory cortex)
how do mechanoreceptors from upper and lower body differ?
mechanosensory nerves from face also differ and they will be shown in another slide
mechanosensory receptor from face path
differ from mechanoreceptors from upper and lower body

enters at the midbrain
what do proprioceptors do?
provide information about the position of the limbs and other body parts in space
diagram showing the somatic sensory numbers, and big picture of secondary somatic sensory cortex
what are dermatomes....what's special about them?
A closer inspection of this crude division into pathways conveying mechanosensory information from the upper, lower bodies and the face reveals more detail

In fact, sensory neurons within each dermatome of the skin surface “projects to” to a particular area within the somatosensory cortex (S1).

Sensory neurons with dendritic fields in neighboring areas of the skin surface project to neighboring areas of the cortical surface.

Creates a “somatotopic map” of the body surface which devotes more cortical surface to areas of the skin with greater receptor density.
what makes up the brainstem?
midbrain, pons, and the medulla
draw a somatotopic map of humans
corical columns
Within each little section of the cerebral cortex – dealing with a particular part of the skin - are columns of neurons with overlapping receptive fields that are arranged perpendicular to the cortical surface

each column of neurons tends to respond to a similar kind of sensory stimulus (e,g, vibration, touch, pressure etc.)

Sometimes these columns are grouped to create a little columnar module that might, for instance, process information from an individual whisker on a rodent’s snout.

These modules sometimes stain differently from surrounding tissues and so can be visualized.
basics of pain perception and experiment that demonstrated that nociception involved specialzed neurons
Is a sensory modality that is related to, but separately perceived from mechanoreception.

The perception of pain does not simply arise from saturation of the response of mechanoreceptor or thermoreceptor neurons by intense stimuli.

Rather……
Painful stimuli are detected by specialized high-threshold sensory neurons called nociceptors.

The nociceptive pathway is a sub-division of the somatosensory pathway, involving similar, but distinct cell types

stimulus is a heat stimulus on the fingers
pain perception also called?
nociception
phases of pain?
1)rapid sharp pain to spinal cord
2)later dull burning pain

B and C represent blocking one of the axons so that the pain is not transmitted.
active ingredient of chilis

picture of receptor
A subset of the small, unmyelinated “C” fibers
have non-specific cation channels in their dendrites that can be opened by Capsaicin – the active ingredient of chile peppers
contralateral
opposite side
ipsilateral
same side
hemisection
damage to one half of the spinal cord...remember spinal cord has 2 sides of dorsal root ganglions
what would happen if a hemisection of the T10 spinal cord occured?
due to the fact that the nerves from pain and mechanoreception change sides
pain and temperature pathway in the body
pathway crosses over immediately and travels up contralateral spinal cord
referred pain...2 examples

2 weird examples also
Because information from visceral pain sensory neurons is merged with those from
the skin in the CNS, pain in the viscera is often “referred” to the skin

“Referred pain” brings up an important point concerning the functioning of somatotopic maps. Namely…… LABELED LINES OF INFORMATION FLOW IN THE CNS

Neurons in CNS pathways are “labeled” in terms of the perceptions they evoke. It doesn’t matter how they are stimulated originally – neurons in a particular pathway will evoke the perception that they are “labeled” with.

In the case of “referred pain”, when neurons in the CNS that are labeled as receiving information from the skin are instead activated via visceral sensory neurons, what is perceived is still the “label” – pain on the skin surface.

As another example, consider placing pressure on your eyeball. What you perceive is light – due to the modulation of the activity of retinal neurons by the pressure. The information from these neurons are “labeled” in the CNS as indicating changes in the intensity of light.

Labeled lines are also responsible for the referred pain known as
phantom limb syndrome – thought to be due to the continued spontaneous activity of
central neurons that would normally have received information from that limb
analgesics
compound that reduces pains intensity
peripheral sensitization of nociceptors
-creat a more painful feeling to help with healing and prevent further injury

-prostaglandins contribute to peripheral sensitization by binding to Gpro receptors that increase levels of cAMP...also reduce the threshold depolarization required for AP's

other factors are responsible for vasodilation and swelling.
pain perception overview and different pathways
There is plenty of evidence that our perception of pain can be enhanced or depressed by the CNS

Ignoring pain during sports or battle

Ability of mechanoreceptive stimuli to reduce perception of pain (acupuncture?)

A variety of neuronal pathways have been defined in the CNS that modulate the perception of pain. These converge on the second order “projection” nociceptive neurons in the dorsal horn that transmit pain information up the anterolateral system to the medulla
gate theory of pain
activation of mechanoreceptors can inhibit the transmission of ascending pain signals

if you hit your shin hard, it will feel better if you rub the overlying mechanoreceptors

C fiber is the nociceptor
A fiber is the mechanorecptor
draw a scheme of nociceptor inhibition in the dorsal horn
descending input is from Raphe nuclei
where is light focused in the eye?

anatomy of eye
back, interior surface of the eyeball....which is covered with the retina-the neural layers of the eye

The retina has many layers of cells.

Oddly, the photoreceptor cells (rods and cones) are at the back of the retina – facing towards the back of the eye - with their outer segments buried in a pigmented epithelium that absorbs scattered light.

This is not a problem, since the layers of the retina lying over the photoreceptors are largely transparent and the visual tends to ignore any stationary shadows cast by blood vessels and nerves overlying the photoreceptors

Iris: colored portion of eye

pupil: black part of eye

sclera: outermost tissue layer...the white stuff

cornea: transparent tissue that permits light rays to enter the eye

aqueous humor: fluid in the eye

Optic disk: blind spot where nerves come from

Fovea: center part of macula where acuity is the greatest
types of eye defects
emmetropia: normal vision

myopia (near sighted): too much curvature of the cornea or by the eyeball being too long. image of distant object focuses in front of, rather than on, the retina

hyperopia: farsighted, eyeball being too short or the refracting system too weak
do photoreceptor cells have action potentials?
no
how does information flow from the retina?
Light is absorbed by the photoreceptor (rod or cone) outer segments. This triggers a change in their membrane potential that is graded with light intensity (no a.p.s!)

The change in photoreceptor membrane potential is transmitted to the bipolar cell by the photoreceptor-bipolar cell synapse. As a result there is a change in bipolar cell membrane potential that is also graded with light intensity (no a.p.s!).

The change in bipolar cell membrane potential is transmitted to the ganglion cell by the bipolar - ganglion cell synapse. Unlike the bipolar and photoreceptor cells, the ganglion cells has V-dependent sodium and potassium channels and so can generate action potentials
As a result of illumination there is a change in ganglion cell membrane potential that results in a change in ganglion cell action potential frequency.

The frequency of action potentials produced by the ganglion cell is graded with light intensity.

The action potentials travel along the ganglion cell axons in the optic nerve to the brain
unaccommodated and accommodated eye picture
unaccommodated:cilliary muscles relaxed

accommodated: near objects...ciliary muscles contracted..reduces the tension in the zonule fibers allowing the lens to increase its curvature which allows for short distance..

When the cilliary is relaxed you can see long distance

Circular muscles cause less eye dilation

pupil muscles create more eye dilation
structural difference between rods and cones
Rods are much more sensitive than cones. They generate large responses to single quanta of light but their response saturates in daylight.

Rods are slower than cones (linked to higher amplification). They take longer to respond and their response lasts longer – less temporal sensitivity.

Rods are mostly found in the peripheral retina – the fovea contains only cones, packed at v. high density.

Consequently, cones are good for capturing rapidly changing detailed images under daylight conditions. Rods are better for imaging in dim light, when amplification and quantum capture is important.

Rods express only one rhodopsin (gene) which absorbs in the green part of the spectrum. A cone may express one of three different rhodopsin genes, absorbing in the red, green or blue part of the spectrum.

So comparison of output from the three cone types can be used for color vision in daylight – no color vision from rods at night.
intracellular recording from a single cone or rod stimulated with different amounts of light
response is hyperpolarization

cell in dark is depolarized to -40mV

In the light, it is hyperpolarized by decreasing permeability to calcium channels
mechanism of visual transduction....picture, but basic
light causes the channel to close so that no sodium and calcium will enter.
picture of rod photoreceptor
Absorption of light causes the retinal to go from a cis conformation to a trans conformation
photoreceptor phototransduction pathway in rods
-change in retinal structure activates transducin, which in turn activates a PDC.

This PDE hydrolyzes cGMP, reducing its concentration in the outer segment and leading to the closure of channels in the outer segment membrane
difference between rods and cones
Rods are much more sensitive than cones. They generate large responses to single quanta of light but their response saturates in daylight.

Rods are slower than cones (linked to higher amplification). They take longer to respond and their response lasts longer – less temporal sensitivity.

Rods are mostly found in the peripheral retina – the fovea contains only cones, packed at v. high density.

Consequently, cones are good for capturing rapidly changing detailed images under daylight conditions. Rods are better for imaging in dim light, when amplification and quantum capture is important.
cone/rod spectrum in light
Scotopic: only rods

Once at Photopic, only cones make a difference because rods do not respond to intensity changes and thus are maxed out.

mn: scott was a mess in his photos
distribution of rods and cones in the human retina
cones are present at a low density throughout the retina, with a sharp peak in the center of the fovea...rods a re present at high density throughout most of the retina, with a sharp decline in the fovea. rods are absent in the foveola
picture of fovea and foveola cells
how many rhodopsin genes do rods express and what do they absorb?
1 gene and green part of the spectrum
what spectrum can cones absorb in?
red
green
blue
is there any color vision output from rods at night?
no
color vision of cones and rod chart
what is special about the red an green cone pigment?
genes lie close to each other on the X chromosome

Men with only one copy of these genes are more susceptible to colorblindness due to defects in these genes than are women (XX) who have two copies
genetic alteration that causes deficiencies in color vision
if there is alterations in the green gene, two of them can cause it to appear red
what happens to photoreceptors in response to light?
they hyperpolarize and decrease their neurotransmitter release
essentially what are ganglion cells good at?
they are sensitive to differences between the level of illumination that falls on the receptive field center and the level of illumination that falls on the surround....luminance contrast
receptive fields
Responses of retinal ganglion cells (r.g.c’s) to light

All r.g.c’s display some spontaneous a.p. activity – even in darkness.

Many r.g.c’s adapt to prolonged stimuli (The change in a.p frequency decreases with time after light onset)

Each retinal ganglion cell has a “receptive field”
The area of the retina (or the equivalent section of visual space) within which light elicits a response from the cell.
r.g.c receptive fields are always circular, and cover about 1 degree of visual space.

Retinal ganglion cells fall into two types with slightly different receptive field properties:

On-center r.g..c’s
Respond to illumination of the center of the receptive field with an increase in a.p. frequency

Off-center r.g..c’s

Respond to illumination of the center of the receptive field with an decrease in a.p. frequency

Illumination of the “surround” the area surrounding the center of the receptive field has the opposite effect to that of illuminating the center

On-center r.g.c’s
Respond to illumination of the surround of the receptive field with an decrease in a.p. frequency

Off-center r.g.c’s
Respond to illumination of the surround of the receptive field with an increase in a.p. frequency

So r.g.c’s have “circular center-surround” receptive fields.

Why? – what benefit is this to vision?

It means that r.g.c’s are maximally stimulated by edges and lines, where intensity changes rapidly, and NOT by uniform illumination – they are “edge detectors”

“Edge detection” is a form of spatial image filtering – allows more “bandwidth” to be allocated to edges and lines during transmission of information along the optic nerve.


- and + indicate a sign conserving synapse or a sign-inverting synapse

Remember cones and rods are hyperpolarized in response to light and release less glutamate...bipolar cells also release glutamate...glutamate is an excitatory NT

On-center cells have a cGMP gated Na channel when bound to Glutamate...Off-center have a ionotropic receptor AMPA that causes the cell to depolarize to glutamate.
draw the scheme for stimulating the center and surrounding of on an off center ganglion cells
illumination of the surround antagonizes illumination of the center
draw a schem for the rate of discharge of an on-center ganglion to a "spot" of light....should include a curve
draw a scheme for the enhanced edge-detection by retinal ganglion cells
cells totally in light or darkhave little or no difference in response to uniform light or dark
what would AP's look like for a light spot in the center of an on and off center ganglion
what would the voltage look like for a dark spot in the center of a ganglion cell
describe the circuitry responsible for generating the receptive field surround of an on-center retinal ganglion cell
also look at picture on page 6 of 10/30 notes for a visual picture of how horizontal cellswork

Horizantal cell receives input via GAP junctions from photoreceptor terminals...When horizantal cells are depolarized they release the inhibitory nt GABA back on to retinal cells. When GABA is not released, the cone and rods become depolarized and reduce the light evoked response. Ultimately this reduces the firing rate of the on-center ganglion cells.
What creates the center of the receptive field?
the vertical information frlowing from the center cone to bi polar cells>ganglion cells

off center and on center
what creates the surrounding of the visual field?
lateral connections via horizontal cells
fovea
The fovea, also known as the fovea centralis, is a part of the eye, located in the center of the macula region of the retina. [1] [2] The fovea is responsible for sharp central vision (also called foveal vision), which is necessary in humans for reading, watching television or movies, driving, and any activity where visual detail is of primary importance.
Iris
Color part of the eye
Pupil
open black part of the eye
Cornea
clear transparent outer layer covering pupil and Iris
Sclera
White part of eye around cornea
fluid in the eye
vitreous humor
Retina
what receives light and detects an image
explain how horizontal cells work
horizontal cells receive input from photoreceptor terminals linked via GAP junctions

they influence the release of neurotransmitter directly onto photoreceptor terminals, regulating the amount of transmitter that the photoreceptors release onto bipolar cell dendrites

Glutamate release from photoreceptor cells depolarizes horizontal cells....This causes GABA to be released by horizontal cells which has an inhibitory effect on photoreceptor cells.

As a result, horizontal cells work to prevent changes in photoreceptor cells.

Horizontal cells are the reason that there is a surround field around the center visual field.
Draw the typical visual field and how it would be produces when it goes through the eye
everything is inverted

top goes to bottom...right goes to left....

Likewise nasal visual field is actually temporal on the retina surface
draw a left and right monocular visual field and how it would be produced on the retina
a
draw the visual field and how various points would be projected onto the retina....How would these lead to the brain?
nasal-contralateral....crosses

temporal....ipsalateral....does not cross
Draw the path of a signal after light is detected....trace the brain pathway
hypothalamus is involved in circadian rhythm: biological clock

Pretectum: reflex control of pupil and lens

Superior colliculus: orienting the movements of head and eyes

Major target is the Lateral geniculate nucleus

MN: hippo protected the cool gent in the cort
diencephalon
contains the thalamus and hypothalamus
the following part of the visual pathway is damaged, what would be the consequence?

right optic nerve
optic chiasm
right optic tract
top part of right optic radiation
all of right optic radiation
How is the visual field represented in the brain
The upper visual field is represented below the calcarine sulcus...lower field above.

left visual field is represented in the right striate cortex
what do neurons in the primary visual cortex respond to?

experiment
They respond selectively to oriented edges

Cat was anesthetized
what is the organization like in the striate cortex
Cells in one vertical column have the same orientation selectivity
Orientation selectivity of columns systematically shifts across v. small regions
Of the cortical surface

So each little part of the cortex (each part of the visual field) is represented by a
complete suite of orientation columns, analyzing line with angles 0 to 180 degrees

lateral geniculate axons terminate in cortical layer 4C
describe how impulses go from the eye to the geniculate nucleus to the striate cortex
Axons from monocularly-driven
neurons in the Lat. Gen. nucleus
terminate on cell bodies of
neurons in layer IV of the cortex.
The layer IV cortical neurons then
send laterally branching axons to synapse on cells in other layers of adjacent cortical areas - these neurons in adjacent areas are then driven by input from both eyes
draw the picture of the parieto-occipital sulcus and the calcarine sulcus
talk about binocular disparities
Some binocularly driven neurons in the cortex are maximally stimulated by a particular
Binocular disparity. These cells can signal the distance of an object

These cells help to complete the the picture because there are normal disparities...at very large disparities double vision can occur.
Talk about M and P cells
M ganglion cells
Transient response
Response not dependent on color
Center and surround driven by all cone types

P ganglion cells
Sustained response
Color opponent center surround receptor fields.
e.g Red ON center. green OFF surround
red light produces a maximal ON response in the center
green light produces a maximal OFF response in the surround
The center and surround must therefore be driven by different classes of cones
Detect color contrast – e,g, a red dot on a green background produces little response, but a red dot on a red background produces a larger response

besides layers in the lateral geniculate being specific from each eye...they are also specific for cell size...cells still go to layer 4c in the cortex

P ganglion cells send axons to the parvocellular layers of the LGN ...M ganglion cells to the magnocellular layers of the LGN.
what is the surround created by
lateral connections
Draw the magno and parvocellular stream
talk about extrastriate cortex in monkeys
V1 is the primary (striate visual cortex)
To which LGN neurons project

Cells in V1 columns send axons
To regions V2 etc.

Each area (V1, V2, Mt etc)
Contains a separate
map of the contralateral
Visual field

Each extrastriate area processes (“contains cells that are especially sensitive to”) a particular set of stimulus features.
e.g.
MT neurons are maximally stimulated by an edge moving in a particular direction in part of the visual field - Motion sensors.
V4 respond selectively to stimulus color without regard to its direction of movement.

Lesion, electrical recording and functional imaging studies indicate that information is transmitted between cells in each area by axonal connections along two distinct visual pathways through the extrastriate areas.
The ventral (object recognition) pathway
V1 > V2 > V4
-color sensitive

The dorsal (spatial vision) pathway
V1>V2>MT
motion sensitive
draw the two pathways from the visual cortex
what is the binding problem
But how is the independent information analyzed in these pathways combined to create a conscious perception of a unified object with color, form and motion?
how is the epithelium in the eye arranged
It is actually at the back of the eye; thus, the photoreceptors are actually covered by the neurons. The only point this doesn't occur at is at the fovea. The epithelium helps to absorb any light that passes through.
what is rhodopsin composed of?
it is composed of opsin and retinal

retinal is a vitamin A derivateve that is the light absorbing portion of the pigment.

when activated by light, the two molecules stop binding
what are sound waves
pressure waves of air generated by vibrating air molecules

Sounds are pressure waves of air generated by vibrating air molecules
A sound wave has a waveform, phase, amplitude and frequency
We can detect sounds having a frequency range of approx 20Hz to 20kHz frequency

Complex sounds can be thought of as being the sum of a large number of sine wave components, each having a different frequency amplitude and relative phase (Fourier analysis).

So the analysis of the auditory system has often proceeded by first analysing its response to sinusoidal sound stimuli.

Amplitude is the max displacement

Frequency is the number of full oscillations per second
talk about phase difference and time delay
The phase difference (q2 - q1) translates into a time delay, t2 – t1
describe the human ear (don't worry about the inner ear)
External ear boosts sound frequency 30-100 fold

Eustacian tube is normally collapsed and is attached to the pharynx....when the pressure needs to be balanced, it is opened.

oval window and round window are small membranous disks
how does the middle ear work?
The bones of the middle ear act as “impedance matching devices”. They act as a
lever with a high mechanical advantage which efficiently transfers airborne
(low impedance) vibrations in the atmosphere to fluid (high impedance) vibrations of the
inner ear.

Movements of the tympanic membrane due to airborne vibration are focused onto
Movements of the oval window and the cochlea fluids beyond
draw cross section of cochlea
vestibuli is the place where the wave enters....attached to the oval window

Sound leaves out of the scala tympani back into the middle ear.
Draw the basilar membrane and surrounding structures
fluid waves push on the flexible membrane of the cochlear duct causing it to transmit a signal

inner hair cells are involved in afferent signals

outer hair cells are involved in efferent signals
What does the basilar membrane of the cochlea contain?
sensory receptor hair cells
Draw a traveling wave in a cochlea that is uncolied
Sound sets up vibration of the oval window, setting up
Traveling waves of basilar membrane vibration
that move the down the cochlea

helicotrema: place where SV and ST contact.

wave goes in the top path first and then through the bottom path
explain vibration amplitudes in the cochlea
Each part of the cochlea
Is “tuned to a separate
Frequency sound

The amplitude of
vibration is greatest in
each region at a particular
frequency

Regions closest to the
Stapes are most sensitive
To higher frequency
Sounds

Regions farthest from the
Stapes are most sensitive
to lower frequency
sounds
draw a picture of shear force
pushing towards the tall stereocilium creates a depolarization....opposite creates a hyperpolarization

Orange points are pivot points

Moving basilar membrane causes tectorial membrane to move

movement causes stereocilium to move
draw mechanoelectrical transduction mediated by hair cells
scheme for the displacement direction of hair cells and receptor potential
Moving at the 90 degree angle does not do anything.
besides having to move in one or the other direction, what else is special about vestibular hair cell?
Response is asymmetrical – depolarizing direction
Is more effective
how does the frequency of a wave influence the depolarization of a hair cell
At low frequencies
hair cell Vm follows the
vibration of sound,
But at high frequencies
Only a smooth
depolarization
persists

Asymmetry occurs because of the fact that the response is asymmetrical and depolarizing direction is more effective
talk about the response properties of auditory nerve fibers
A random sampling
Of electrical recordings from
single auditory nerve
Axons (fibers) reveals that
Each axon is tuned (most
sensitive to) a particular
range of frequencies of
sound)

lowest peak for each curve is the characteristic frequency
response properties of auditory nerve fibers all on one page
The tuning results
from the fact that
Each axon is connected
to a hair cell at a
different place along
The basilar
Membrane of the
Cochlea.

This tuning-by-position
Is the only way that
The brain can discriminate
The frequency (pitch)
Of high-frequency sounds
(>3 kHz) An axon has to be
perceptually “labeled”
According to the position
of its origin along the
Basilar membrane
what happens above 3kHz in the auditory system?
Below 3 kHz, the hair cell membrane potential can “track” the individual peaks of
Pressure during a sound wave (phase-locking),
so that the time intervals between action potentials produced by the auditory nerve
axon can in theory be used by the brain to determine the frequency of the sound

after this the membrane potential is basically stationary
tonotopic organization
neurons are arrayed in brain nuclei and cortex in order of their most-sensitive (characteristic) frequencies
Transmission of information from the auditory nerve sensory neurons to the brain.
Parallel organization of multiple ascending pathways

Auditory nerve enters the brainstem
Branches to innervate 3 subdivisions of the cochlear nucleus
Cochlear nucleus neurons project axons to terminate in the ipsi-and contralateral superior olive in the pons and the inferior colliculus in the mid-brain.
Inferior colliculus neurons project axons to terminate in the
medial geniculae nuceus in the THALAMUS
MGN Thalamus neurons send axons to the primary auditory cortex in the temporal lobe
talk about stereocilia and nerve interaction
one nerve branches to many stereocilia, but one stereocilia is only attached to one nerve
Processing of sound information at lower brain centers:
Role of the medial and lateral superior olives (MSO and LSO) in integrating information from the two ears and localizing the source of a sound

MSO – uses interaural arrival time differences to calculate the direction from which sound is arriving

LSO uses interaural intensity differences
How does the MSO compute the location of a sound
Sound arrives first to left ear...but arrival at neuron E is delayed by a longer axon...path to E is faster from the right ear...sound arrives later though

So, due to the coincident release of NT, activity in E is greatest in response to a
sound coming from the left. Neuron A is most sensitive to sound from the right etc

The neurons A – E of the MSO act as co-incidence detectors
How does the LSO work?
Sound on left side is more intense
– inhibits input from right side -> net
Excitation from left hand side sent to higher
brain centers indicates sound coming from left

Red neuron leading to interneuron to blue neuron is an inhibitory interneuron

LSO using intensity differences
information processing in the inferior colliculus
Neurons with cell bodies in the Inferior Colliculus
are arrayed in such a way as to create an auditory space map.

neighbouring neurons are preferentially sensitive to sound coming from neighbouring directions.
This map is based on the calculated output of the LSO and MSO neurons
-Highly developed in nocturnal predators, like barn owls
information processing in the MGC thalamus
Neurons here mediate the detection of specific, complex sound patterns
E.g. echolocating neurons in bat MGC thalamus are sensitive to particular delays between the time of emission of sound and the time at which an echo is received.
info processing in the auditory cortex
Primary auditory cortex contains a precise tonotopic map – an array of neurons arranged according to their characteristic (best) sound frequencies.

...This is, in effect, a topographic map of the basilar membrane.

In addition, cortical neurons can be binaurally stimulated (by both ears) – strips of neurons excited by one ear, but not the other alternate with strips excited by both ears – similar to ocular dominance columns in the visual cortex

Cortical neurons are also often particularly sensitive to certain sound combinations that characterize the vocalizations of an animal.
special part of the auditory cortex
Wernicke's area...important in comprehending speech
organization of the human olfactory system
Cribriform plate can become damaged if punched in the nose...it is the white stuff....not the yellow stuff
structure and function of the olfactory epithelium
olfactory cilia: inward generator current leads to generator potential

mature receptor cell: generator potential leads to action potential

Axons produce the AP
How often do Olfactory Receptor Neurons renew?
every 6-8 weeks
Show a stimulation of olfactory cells and the measured current
Wholecell patch clamp recordings of generator currents

The cilia are the sensory organelles...contain the transduction machinery
what is the outer section of a rod or cone actually?
it is really a modified cilium
olfactory transduction pathway
Mucous contains odorant binding proteins that deliver odorant molecules to the cilia

Inward current flows when
Odorant is present - generator
Current > depolarizes receptor cell

Chloride flows out because mucous is low in chloride....net inward current
what is it when negative ions leave
net inward current
olfactory receptor molecules
Odorant receptor proteins
are a HUGE
Family of related
G-protein-linked
Receptor proteins

Approx 1000 distinct
Genes in humans code
For odorant receptor
proteins!
3-5% of all our genes!

(compared to only
4 for opsins.)

part of the 7 transmembrane G-pro receptor family
how many odorant receptor proteins does an olfactory receptor neuron express?
1 or at most a few
How could you tell different olfactory receptors apart?
you could use a patch-clamp and see how they responded via their generator current....a downward current is actually a positive voltage
What is an important rule about AP's
their intensity is always the same, but their frequency can change
how does increasing conc of odorant affect AP
extracellular response of aps in olfactory receptor neuron axons to selected odorants
how does each receptor neuron respond?
responds with varying sensitivity to a range of odorant molecules...not exclusively to just one
if we measure the response of only a single odorant receptor, would it be possible to determine what the receptor was responding to...a high conc odorant or a low conc odorant?
no
how does the brain compare which odorant is present?
compare the output of an array of different odorant receptor neurons and then label the specific pattern of activity in response to a given odor as indicating the presence of that odor.

Presumably stimulation with a particular odorant creates a particular pattern of activity across the olfactory epithelium which is then “mapped” onto neurons in the olfactory bulb – a form of topographical mapping

...brain can't label a given neuron to an odorant

...brain must look at pattern of electrical activity and then it can decipher
organization of the mammalian olfactory bulb
Olfactory receptor neuron (ORN) axons project to
Glomeruli, converging to make synaptic contact with Second-order “mitral cells”

In the mouse approx
25,000 ORN’s converge onto 25 mitral cells
in each glomerulus – this convergance amplifies the sensitivity for the
detection of weak
odors

Granule cells are localized interneurons that shape the response of the mitral cells

don't worry about the tufted cell
what explains how ORN's expressing a given odorant protein can be so scattered throughout a region of the olfactory epithelium
ORN’s that express a
Particular odorant receptor
Protein converge onto
a subset of glomeruli
on each side of a rat’s
Olfactory bulb.

This convergence
explains how ORNs
expressing a given odorant
peceptor protein can be
So scattered
Throughout a region
of the olfactory epithelium
how many responses from olfactory receptors can a glomerulus receive?
response from thousands of olfactory receptors, but all from the same sub-set....this is the basis of convergence
what is special about the pattern of active glomeruli
correspond to the pattern of receptor proteins activated by a given odorand....brain can detect previous patterns, it can have an image to oderant
draw a pathway of the olfactory tract
organization of the human olfactory system in the brain