NPB100 Midterm 2

axon growth cone

filopodia

• finger sticking out of axon

lamellopodia

• structure filling in the space between the filopodia

attracted or repelled by certain cues, determined by guidance cue receptors

extracellular matrix molecules

many molecules that axons use to sense environment or grad onto the extracellular matrix or other cells

external cues can be attractive or repulsive

act of binding causes changes inside the cell (e.g. via kinases) to help axon move (e.g. changing cytoskeleton → changes direction of axon’s migration)

growth cone movement

dynamics of growth cone are mediated by 2 processes

• polymerization and depolymerization of actin filaments

• myosin-mediated filaments of actin filaments on microtubules and other internal structures

  • at stationary phase, processes are at equilibrium (no net axon growth or shrinkage)

    • myosin keeps moving along actin and filament depolymerizes behind it & polymerizes ahead of it

  • can change conformation to cause things to move

filopodium contacts attractive substrate

1. actin filaments are immobilized by attachment to substrate

2. actin polymerization causes protrusive growth of growth cone

3. microtubule-attached myosin that interacts with actin filaments now moves microtubules forward

4. axon is extended and stabilized in direction toward attractive substrate

filopodium contacts repulsive substate

1. rapid and complete collapse of filopodium caused by actin depolymerization

2. release of substrate attachments

3. axon will move away from repulsive cue

axons finding their way

molecular mechanisms of axon guidance can act long or short range & be attractive or repulsive (4 possibilities)

• long range cues usually by diffusive gradient

• short-range cues usually bound to substrate

developing pain/temperature sensory axons must cross the spine midline before growing up toward thalamus

netrin

diffusible cue from notochord that guides axon ventrally and (w/ other molecules) across spinal cord

1. axon first expresses receptor DCC, causing long-range attraction to netrin gradient

2. when growth cone arrives at floorplate, resulting signals cause it to change receptors it expresses

3. axon expresses receptor robo that is repelled by another floorplate signal called slit

4. prevents axons from doubling back toward midline

signal response depends on receptor, not only ligand

mechanisms of topographic mapping in vertebrate visual signaling

topographic maps arrange cells with similar function near to each other (very efficient)

surgically rotating frog eye doesn’t prevent axons from finding the correct targets

graidents of both expressed receptors and ligands guide axons to the correct position

• axons with fewer receptors continue farther until ligand concentration is sufficient

making functional synapses

1. initial adhesion/recognition of adhesion proteins and nascent “active zone”

2. further adhesion with induction of both pre- and postsynaptic specialization (important proteins like synaptotagmin and SNARE proteins)

3. localizing vesicle and Ca²⁺ channels presynaptically & localizing postsynaptic receptors → ready

synapse pattern and number

initial pattern of neuronal connections is refined to reach adult pattern

“regressive” events occur mostly through competition

• cell death (apoptosis), axonal/dendritic pruning, synaptic elimination

neurotrophins

acts on neurites (dendrites, axons)

sustains the cell body but allows specific, regional growth where it is needed

mechanotransduction

mechanosensory and pain/temperature pathways take different routes to the brain

pain/temp cross immediately and then ascend; mechanosensory ascends then crosses higher up

(pseudo-) unipolar somatosensory neurons

soma in dorsal root ganglion

can have a receptor rather than true dendrites

AP initiated distally, goes right past soma (soma doesn’t do anything with AP)

axon hillock is not on the soma

transduction in mechanosensory

mechanical deformation increases probability that mechanotransduction channels open

cations enter → depolarization (amount is graded/ not all-or-none)

induces an AP in axon nearby (not at cell body)

more stimulus will induce more frequent AP

• graded potentials → rate code

skin mechanoreceptors

depth of receptors in skin tissue largely determines receptive field size (deep = large)

structure of receptors helps determine temporal response (slowly vs. rapidly adapting)

receptive field

somatosensory receptive field size correlates well with receptor density in skin

more dense receptors = smaller receptive fields = better discrimination

adapting mechanoreceptors

somatosensory receptors differ in how they respond in time

slowly adapting receptors are useful for distinguishing static representations (pressure, object, shape)

• good for sensing continuous things

rapidly adapting receptors are useful for detecting dynamics

• good for sensing onsets and offsets

proprioreceptors in musculoskeletal system

muscle spindles

• detect muscle length (like joint angle) & can be calibrated

• extrafusal fibers stimulated by alpha motor neurons

• intrafusal muscle fibers senses lengthening of muscle through afferent fibers & gamma motor neurons stretch fibers to sense if muscle length is still changing

golgi tendon

• detect tendon tension

dorsal column - medial lemniscal system

where mechanosensory information is conveyed

enters via the DRG, ascends, crosses in the brainstem (medulla), and ascends further through the thalamus (VPL) to cortex

topographic maps

body plan is represented topographically in many regions from spinal cord up through cortex

computationally efficient (similar function neurons nears one another)

neurons in primary somatosensory cortex

cortical neurons are organized into functional units or modules that span entire depth of cortex: columns

• different submodalities for the same body area are segregated in different columns → rapidly and slowly adapting

brain plasticity

representations in brain can change dramatically with

• large change in input statistics (amputation)

  • if finger is amputated, neurons from other areas take over the neurons from amputated finger

• behavioral relevance, importance, practice

rapid plasticity could be due to “silent” synapses being activated

slower plasticity could be due to neurons growing new dendrites/axons

pain and temperature

pain, temperature, and non-discriminative touch (course, sensual) are conveyed by anterolateral system

pain is conveyed via different neurons from non-noxious heat (warm) or touch stimulus

first and second pain

fast, sharp pain and slow, dull pain arise from different afferents

A-delta fibers are fat, mylienated = fast conducting

C fibers are thin and unmylienated = slow conducting

• achy pain

transient receptor potential (TRP) channels

many receptors in pain and temperature pathways have similar structure

responds to temperature but also many other noxious stimuli (mechanical, acidity) & non-noxious ligands (cannabinoids)

noxious-hot temperature signal also activated by capsaicin (hot peppers)

inflammatory response to tissue damage

tissue injury causes a chemical mixture that affects pain, inflammation and subsequent healing

some chemicals like prostaglandin can increase the perception of pain (hyperalgesia), even to previously innocuous (non-damaging) stimuli (allodynia)

phantom limb

amputees can have pain or other sensations in missing body part

70%

• first few weeks post op

• burning, cramping, other qualities of phantom pain in missing limb

50%

• suffers 7 years later or some are life-long continuous or intermittent

pain pathways

sensory discriminative (first pain)

• anterolateral system → ventral posterior lateral nucleus → somatosensory cortex (SI, SII)

affective-motivational (second pain)

• anterolateral system → anterior cingulate cortex and insula

mirror box treatment

shows that phantom pain often relies on a mismatch of the body plan with the sensory inputs

can help with phantom pain by letting the amputee see two hands in the mirror and do activities to trick the brain into relieving pain

pain descending pathways

descending pathways can modulate pain

• like through endogenous opioids (enkephalins, endorphins) or endocannabinoids

• reduces amount of neurotransmitter released by C-fiber

the eye

cornea bends light the most

lens can accommodate to focus on different distances

in older adults, lens loses elasticity and cannot focus on near objects

structure of retina

retina is arranged “backwards” with the photoreceptors in the back

pigment epithelium

• recycles photoreceptor disks

• regenerates photopigment molecules after they’re exposed to light

phototransduction

photoreceptors hyperpolarize when exposed to environmental energy/stimulation (light)

depolarization causes Ca²⁺ influx and transmitter release

in the dark, photoreceptors are continuously depolarized and release a lot of neurotransmitters

phototransduction mechanism

dark

• cGMP is synthesized and allows Na+ to flow in with K+ efflux

light

• cGMP is reduced and there is reduced Na+ influx

• there is still K+ efflux

photoisomerization

absorbing a photon changes the molecule’s shape and its function

opsin

light stimulates and causes a G-protein coupled cascade that shuts the outer segment Na+ and Ca2+ channels

rod photoreceptors

huge amplification in rods

• 1 photon = 200 ion channels closed = 1mV change

cones amplify much less than rods and need about 100 photons to elicit a response

luminance and color

rods have greater light sensitivity than cones but have poor spatial resolution & no color discrimination

rods saturate at a lower light level (all Na+/Ca2+ channels closed)

many more rods (90 million) than cones (4.5 million) but distributed differently

cones alone convey central vision

absorption spectra of rods and cones differ due to different opsins (photopigments)

rod convergence

rods have greater convergence onto bipolar cells than cones

contributes to rod’s ability to signal in very low light

gives cones better spatial resolution - ability to represent detailed features

people without cones are legally blind, whereas people without rods cannot see in low light (night blindness)

abnormalities of color vision

8% of men and fewer women have red-green color blindness from lack of one photopigment or a hybrid pigment between red (long wavelength) and green (medium)

center-surround receptive fields

ON-center

• light spot in the center and the periphery vision is inhibited

• ON-center bipolar is stimulated by light & has an inhibitory synapse

• light enters → hyperpolarizes photoreceptor → depolarizes ON-center bipolar → depolarizes ganglion

• no light enters → depolarizes photoreceptor → hyperpolarizes ON-center bipolar → hyperpolarizes ON-center ganglion

OFF-center

• dark spot in the center and the periphery vision is not inhibited, center is inhibited instead

• OFF-center bipolar cell is inhibited by light & has an excitatory synapse

• light enters → hyperpolarizes photoreceptor → hyperpolarizes OFF-center bipolar cell → hyperpolarizes OFF-center ganglion

• no light eneters → depolarizes photoreceptor → depolarizes OFF-center bipolar → depolarizes OFF-center ganglion

photoreceptors → bipolar cells → ganglion cells

responses of ON-center ganglion cells to different light conditions

if you only focus light on the center spot, then there will be the most response

if you fill the center spot and all of the periphery, there will be most limited responses

lateral inhibition

light on the surround affects center RGC center through withdrawal of lateral inhibition

1. light on surround cone causes it to hyperpolarize

2. removes excitation of horizontal cell

3. removes inhibition from center cone, causing it to depolarize, an opposite effect as compared to light in the center

when no light shines on surround → it hyperpolarizes the center → depolarizes ON-center bipolar cell → depolarizes ON-center ganglion

what good is center-surround

emphasizes edges, the most informational attributes of visual perception

provides an efficient neural code to represent visual input (not wasting much “effort” on uniform illumination)

Hermann Grid Illusion

ON-cell whose receptive field is at intersection has larger area of inhibitory surround exposed to light

• corners of black squares are in the surround as well as light in the center

makes brain think there is less light there → perceived darkness at intersections

dark blobs disappear when foveated because foveal RGCs have smaller receptive fields that don’t extend much beyond the crossings

magnocellular (m) retinal ganglion cells

large cells with large receptive field, abundant in peripheral

not color sensitve

transient response (rapidly adapting)

signals motion

parvocellular (p) retinal ganglion cells

small cells with small receptive fields, abundant in fovea

color sensitive

sustained response (slowly adapting)

signals form and detail

koniocellular (k) retinal ganglion cells

small and maybe color sensitive