Neuroscience Final

Individual neurons form neural circuits (PYR, PV+, SST+, VIP+)

PYR: pyramidal neuron

PV+: Paravalbumin-expressing interneuron

SST+: Somatostatin-expressing interneuron

VIP+: Vasointestinal peptide-expressing interneuron

Why study neural circuits?

The postsynaptic effect of a single action potential is small

Population coding is a common theme in neural information processing

Neural Coding

1. Action Potential Frequency (rate code)

   1. The firing rate (frequency of APs) code for the strength of a sensory signal

2. Coordinated activity (synchrony code)

   1. Precision of spikes among different neurons

3. Graded Potential

   1. The amplitude of depolarization codes for the strength of the sensory signal; the more depolarization, the more transmitter is released

Examples of Neural Systems

Visual, Somatosensory, auditory, motor, reward, learning/memory

Example study of synchrony code

EEG (Electroencephalography) recording during “moony face recognition” in human subjects

• Higher spectral power: stronger synchrony

Properties of Sensory Systems: Central Pathway

Sensory signal is transmitted from peripheral neurons to “central” neurons in the brain

Periphery → Subcortical → Cortical

Properties of Sensory Systems: Sensory Receptors (Cells)

Modality specific

Transduce energy of different forms to electrical activity so that can be passed on to other neurons

Even within a single sensory system, different populations of neurons are specialized to detect different features of the same input

Properties of Sensory Systems: Topographic Map

Nearby neruons have nearby receptive fields → orderly representation of the sensory space in the nervous system

The Visual Pathway

Retina →

1. Suprachiasmatic Nucleus (SCN)

2. Superior Colliculus (SC)

3. Lateral Geniculate Nucleus → Visual Cortex: V1 → V2→ V3, V4, V5

Light starts visual processing

Electromagnetic radiation that is visible to our (human) eyes: 400 (higher energy) to 700nm (lower energy)

Light Energy to Neural Activities is called

Phototransduction; occurs in the retina

how light energy leads to a change in membrane potential

Iris

Surrounds pupil/eye color/contains muscles that can change the size of pupil (controls amount of light reaching the eye)

Sclera

continous with the cornea/”white of the eye”; is a tough outer wall

Extraocular muscles

move the eye

Retinal Information Processing: 1 pathway

Linear Pathway (Direct):

Photoreceptor Cells (P): (only cell type directly affected by light) → Bipolar Cells (B) → Retinal Ganglion Cells (R) : The retina’s only output cell type

Retinal Information Processing: 2nd pathway

Lateral Pathway (Indirect):

Retinal Ganglion Cells ←> Amarcine cells <→ Bipolar

Bipolar ←> Horizontal Cells ←> Photoreceptor cells

Cones detect light of specific wavelength

Blue Cones: 430nm

Green cones: 530nm

Red cones: 560nm

Distance across retina

Temporal Periphery Central Retina Nasal Periphery

Photoreceptor cells are constantly depolarized in the dark

Intracellular cyclic guanosine monophosphate (cGMP) binds to cGMP gated Na+ channel → cGMP keeps the channel open and allows Na+ influx → Photoreceptor cell membrane is kept depolarized (-30mv)

Dark Current → NT glutamate is constantly released at the terminal

Photoreceptor cells are hyperpolarized by the light

Light stimulation reduce cGMP → The Na+ channel close, allows the membrane hyperpolarization (-65mv) → glutamate release stops at the terminal

Neural Codes

the meaning of activity (action potentials) by a neuron depends on the system it’s part of

AP by neurons in a pain system, would yield the perception of pain

AP by neurons in visual system would yield the perception of vision

APs by a neuron in motor systems would cause movement

APs by a neuron in system underlying emotion might cause feeling of fear or another emotion

Systems have _ and neurons in _ code for _

Systems have subsystems and neurons in different subsystems code for different functions

Visual subsystem example

In visual system different areas and groups of neurons perform different functions

Some neurons responsible for detecting the form of a visual object, others responsible for detecting color, others for movement, others for location (code to location of an object in visual field)

What is a neuron coding? What attribute of the visual world is a neuron in the visual system encoding?

refers to how a neuron represents information through its electrical activity (like firing rate or pattern of action potentials)

encodes attributes such as orientation, color, motion, depth or location of visual stimuli in the visual field

How do neuroscientists determine the function of a neuron or of a system of neurons?

By recording their activity (using electrodes, imaging, or fMRI) while presenting specific stimuli or tasks, then analyzing how firing patterns change

They may also manipulate the neurons (lesions, electrical stimulation, optogenetics) to see how behavior or perception is affected

Retina

Consists of several thin layers of cells distributed across the inside of the eye

Contains photoreceptors that convert light into neural signals (light → images sent to the brain)

Fovea

The center of the visual field, provides color vision

Light directly reaches to the photoreceptor cells here

Less distortion, less blur → clear vision

It is the portion of the retina with the highest acuity, the ability to resolve fine detail and patterns of light

Visual Acuity

The ability of the eye to distinguish two points near eachother

Optic Disk

is the retinal location where axons from a type of retinal cell collect and exit the eye and form the optic nerve

What is the blind spot and why

The optic disk because there are no photoreceptors

Lens

Fine tunes focus by helping the eye focus light onto the retina and adjust refraction for near and far vision

Cornea

Covers pupil and iris

Bends (refracts) light toward retina (main refractive surface of the eye)

Pupil

Controls how much light enters the eye (goes to retina)

Optic Nerve

Sends visual info to the brain

Properties of Sensory Systems: receptive field

the location in the environment (or the surface of the body, i.e, sensory space) from which an appropriate stimulus will change that cell’s activity

Photoreceptor Receptive Field

1. is circular

2. of a given photoreceptor is determined by its location in the retina

3. responds to changes of light intensity in its field

RGC A (peripheral) has la arger field than RGC B (Central)

Divergence of single PR cells onto multiple RGC → overlapping fields

Example of neuron’s receptive field

Light at point a (near the fovea) will affect the activity of retinal cell in location “a” in the retinal”

Cells in different locations in the retina have receptive fields in different locations in the visual fields

The cells activated by

Retinal Ganglion cells, Amacrine, Bipolar and Horizontal cells: activated by signal from photoreceptor cells

Photoreceptor cells: directly activated by light

Receptive Field Size Difference in Distinct RGC types

In perpiheral: convergence of synaptic input: large field; magno (m)-type

In central: no or less convergence of synaptic input: small field; parvo (p)-type

RGC Receptive Field: Center-Surround

On-center: increase spiking when light is on the center receptive fieldl increases APs

Off-center: increase spiking when light is off the center receptive field; decreases Aps

Two Different Glutamate Receptors in Bipolar Cells: Inhibitory Glutamate Receptor

Glutamate release from pre-synapse in PR cell → Received by inhibitory receptor at post-synapse in BP cell → Decrease membrane potential in BP cell → No NT release

Two Different Glutamate Receptors in Bipolar Cells: Excitatory Glutamate Receptor

Glutamate release from pre-synapse in PR cell → Recieved by excitatory receptor at post-synapse in BP cell → increase membrane potential in BP cell → NT release

Mechanism of BP cell response to receptive field Surround

Horizontal cell depolarization → photoreceptor cell inhibition + bipolar cell excitation

Visual Preception Does NOT depend on _ and why?

Illumination level

Contrasts in light intensity are more informative than the overall illumination. so that our perceptions of what we see are not dramatically affected by the level of ambient illumination

5 cells types in the retina

1. Photoreceptors

2. Bipolar cells

3. Retinal ganglion cells

4. Horizontal cells

5. Amacrine cells

Photoreceptors

a specialized neuron in retina that detects light and converts it into electrical signals

only cell type in visual system that’s directly sensitive to light

two types: rods & cones

project to the bipolar cells

Rods

Highly sensitive to light, responsible for vision in very dim light

Bleached in bright light and thus unresponsive in bright light

Not responsible for high acuity vision (not good for fine detail)

Achromatic (insensitive to colors/ so black and white vision)

Only exist outside of the fovea

120 million rods in human retina

Cones

Low sensitivity: Less sensitive to light intensity and are inoperative in dim light

Needs a lot of light

High resolution

Sensitive to color, three subtypes: selectively sensitive to red, blue, and green wavelengths light

Most concentrated in the fovea

6 million

Bipolar cells

relay signals from photoreceptors to ganglion cells

Retinal ganglion cell

sends action potentials to the brain via the optic nerve

Horizontal cell

integrates signals across photoreceptors

excited by increased glutamate and release GABA (inhibitory) which inhibits nearby photoreceptors, sharpening the contrast (lateral inhibition)

Amacrine cell

regulate bipolar and ganglion cell communication

located btwn bipolar & ganglion cells and used input from bipolar cells to modify the input using GABA or glycin to inhibit some ganglion cells in order to help detect motion, edges, direction

Emmetropia

Normal vision

Hyperopia 

refractive error 

farsighted

Hyopia

refractive error

nearsighted

Why is it that only retinal ganglion cells have axons?

axons are needed for long-distance transfer of info

in retina the cells are close together so they don’t need APs or axons

also, communication by PSPs may be able to convey info that is more subtle than can be conveyed by the AP frequency code

Why do only RGCs and Amacrine cells generate action potentials?

The rest of the cell types use graded depolarization to release neurotransmitter to the next cell

A depolarization increases NT release

Small depolarizations cause small release of NT; large depolarizations cause large release of NT

Relationship between diff cell types in retina

retina is “inside out” w photoreceptors furthest away from light (very back of ete), all light must pass thru other cell types to reach photoreceptors

works bc all cells in eye (except photoreceptors) are translucents

also at the foveal pit all cell types (except photoreceptors) are pushed out of the way

resting membrane potential of photoreceptors 

-30mv in the dark

maximum hyperpolarization

-65mv and produced by bright light

Glutamate

neurotransmitter used by photoreceptors. the greater the intensity of light, the less NT released

Visual Pathway route

Eye → optic nerve → optic chiasm → optic tract → Lateral Geniculate Nucleus → Optic Radiation → primary visual cortex

A-F & right vs left visual hemifields

Right eye, optic nerve, optic tract will see left visual hemifield: A, B, C

Left eye, optic nerve, optic tract will see right visual hemifield: D, E, F

Bioncular visual field: B, C, D, E

Fixation point is between C and D

Lateral Geniculate Nucleus (LGN)

six distinct layers

Layers 1 & 2 contain larger cells: Magnocellular layer

Layers 3-6 contain smaller cells: Parvocellular layer

Each layer recieves inputs from one eye

Parallel Processing of Different Visual Properties

Layer 1: contralateral, magnocellular

Layer 2: ipsilateral, magnocellular

Layer 3: ipsilateral, parvocellular

Layer 4: contralateral, parvocellular

Layer 5: ipsilateral, parvocellular

Layer 6: contralateral, parvocellular

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Ventral to each principal layer: nonM-nonP (Koniocellular LGN cell type), contra/ips it’s same as overlying prinicpal layer

Topographic Map in V1

Visual Field:

Left top: 1 & A

Left bottom: 2 & B

Right top: 3 & C

right bottom: 4 & D

V1 cortex:

Right hemibrain posterior: 1 & A Anterior: 2 & B

Left hemibrain posterior: 3 & C Anteriror: 4 & D

Suprachiasmatic Nucelus

Circadian rhythm: 24 hr fluctuations of biological processes

Recieves inputs from intrinsically photosensitive RGC (ipRGC)

Topographic map in Superior Colliculus

Axons from RGCs in both eyes that are activated by the same object in the visual field converge onto the same neurons in the SC

Right eye sees: BC, DEF → right superior colliculus (posterior): ABC

Left eye: ABC, DE → left superior colliculus (posterior): DEF

Layered Structure in SC

← Anterior Posterior →

C B A

Superficial layers Visual input

Intermediate and deep layers Visual, auditory, somatosensory input, motor outpu

Sensory neurons directly synapse onto motor neurons to control movements, such as gaze and saccades

Cortical Visual Subsystems

Retina → LGN → visual coretex V1 → V2 → V3, V4, V5

Blindsight pathway

Retina → superior colliculus (can track/avoid objects subconsciously) → Suprachiasmatic Nucleus (circadian rhythm intact)

(no LGN/Visual cortex)

Parallel Processing Streams in the Perceptual Visual Pathway

Dorsal stream: movement; V1 → V3 & V5

Ventral Stream: color; V1 → V2 → V4 → Inferotemporal cortex (IT): complex objects

Rhodopsin

photopigment; a light sensitive receptor protein in rod photoreceptors

made of 1. the protein opsin (GPCR) and 2. retinal (11-cis-retinal or trans-retinal)

How does light produce the graded hyperpolarization?

The ligand-gated Na+ channels in the outer segment membrane are open in the dark, causing depolarization (to the resting membrane potential of -30mv)

These ligand-gated channels r like receptors, but “inside-out", meaning they bind their ligand cGMP to a binding site on the intracellular face of the Na+ channel and this opens the channel

How does light decrease the concentration of cGMP?

1. photopigment (highly concentrated in membrane of disks in outer segement of photoreceptors) is purple in dark, when it absorbs light its bleached to pale yellow

2. Photopigment is rhodopsin

3. The steps of cGMP activation

Rhodopsin: retinal

the only light sensitive molecule in visual system

precursor of retinal is vitamin A

exists in 2 confromations:

1. in the dark: 11-cis-retinal

2. in light will switch it to: all trans-retinal 

Steps of cGMP activation

1. Opsin passes thru membrane 7 times (it’s a metabotropic or G-protein-coupled receptor)

2. release of retinal from opsin allows opsin to change shape and this activates a G-protein (transducin)

3. The G-protein (G) dissociates and travels along the membrane and activates an enzyme (cGMP phosphodiesterase)

4. cGMP phosphodiesterase converts cGMP to GMP, and thus lowers the concentration of cGMP

5. In the dark, cGMP bound to Na+ channel. light decreases concentration of cGMP, causing cGMP to disassociate from the channel, consquently, channels close and photoreceptors hyperpolarize

Why do we have this type of system (what’s the advantage)? 1st answer

1. Increased surface area + increased photopigment produced by having the photopigment molecules on the stacked disks, instead of on the Na+ channels, increases the chance of light being detected by a rod

   1. system so sensitive that a single photon can produce a detectable change in the membrane potential of a rod-type photoreceptor

Why do we have this type of system (what’s the advantage)? 2nd answer

The use of G-proteins allows for amplification

each molecule of opsin can activate many G-proteins, each of which can activate many enzymes of cGMP phosphodiesterase, which then can convert many molecules of cGMP into GMP

depolarized photoreceptor

Dark= glutamate released= ON bipolar inhibited OFF bipolar excited

hyperpolarized photoreceptor

Light= glutamate decreased= ON bipolar excited OFF bipolar inhibited

Excited

more likely to send signal to ganglion cell → action potential

Inhibited

less likely to pass signal to ganglion cell → no action potential

OFF bipolar cell

sends signals to OFF ganglion cells → OFF pathway → detects when light turns OFF

ON bipolar cell

sends signals to ON ganglion cells → ON pathway → detects when light turns ON

3 Types of Retinal Ganglion Cells

1. Parvocellular (P-type)

2. Mangnocellular (M-type)

3. NonM-NonP

Parvocellular (P-type)

small receptive fields, sustained response involved in color and detail

Mangnocellular (M-type)

large receptive fields, transient responses, sensitive to motion and low contrast

Each ganglion cell responds to light in a specific area:

its receptive field

1. Center: direct input from photoreceptors

2. Surround: indirect input via horizontal cells

Metabotropic Receptors (how they differ from Ionotropic receptors)

• Linked to G-proteins not ion channels

• slower but long-lasting effects

• acts thru secondary messangers

How they work: NT binds → activates G-protein → starts secondary cascade → affects ion channels indirectly

Ionotropic Receptors (how they differ from Metabotropic receptors)

• ion channels themselves

• fast-acting

How they work: NT binds → channel opens → ion flow in or out → direct change in membrane potential

ON bipolar cells are _ 

Metabotropic since they express mGluR6 receptors (GRCRs)

OFF bipolar cells are _

Ionotropic since they express AMPA or Kainate receptors

The three visual pathways

1. Retinofugal

2. Retinotecal

3. Retinohypothalamic

Retinofugal Pathway

Main conscious vision pathways

Retina → optic nerve → optic chiasm → optic tract → LGN (thalamus) → primary visual cortex

Retinotecal Pathway

involved in eye movement and reflexes 

Retina → Superior Colliculus

Retinohypothalamic Pathway

regulates circadian rhythms

Retina → Suprachiasmic Nucleus (SCN)

Each eye see both visual fields but:

The nasal retina crosses at the optic chiasm

The temporal retina stays on the same side

Left Eye sees

left visual field → hits nasal retina → crosses at optic chiasm → goes to right hempisphere

right visual field → hits temporal retina → does NOT cross → goes to right hemisphere

Right Eye sees

right visual field → hits nasal retina → crosses at optic chiasm → goes to left hemisphere

left visual field → hits temporal retina → does NOT cross → goes to right hemisphere