Nerve Regeneration Exam 2

what are the major classes of non-diffusible axon guidance molecules?

extracellular matrix molecules and their integrin receptors

Ca2+ independent cell adhesion molecules

Ca2+ dependent cell adhesion molecules

ephrins and Eph receptors

what are the most prominent examples of ECM cell adhesion molecules?

laminins, collagens, and fibronectin

what do ECM cell adhesion molecules do?

form polymers and create durable local extracellular substances

what are integrins?

cell surface receptors that bind specifically to ECM cell adhesion molceules

how do integrins functions?

binding of laminin, collagen, or fibronectin triggers a biochemical cascade

how do ECM molecules function in axon growth?

organized sheets of ECM components create the basal lamina, which provides a supportive substrate

How do the CAMs and cadherins function in axon growth?

found on growth cones and targets and can have dual (ligand and receptor) functions

what do CAMs do specifically

fasciculation of groups of axons

what do cadherins do?

help determine the final target

what do ephrin ligands (and their tyrosine kinase receptors) do?

cell-cell recognition to recognitize pathways for growth

how can ephrins be used for reverse signaling?

the extracellular domain of ephrin ligand cleaved or Eph receptors can be removed to limit axon growth

tropic molecules

guide growing axons towards target

trophic moleucles

support the survivl and growth of neurons and their processes once an appropriate target has been contacted

chemoattractant example

netrins

what do netrins do?

proteins localized to floorplate of neural tube and directs axons across midline

what do slit (chemorepellant) and robo (receptor) do

once axon has crossed midline, prevents it from crossing over again

what are the two classes of chemorepellants?

CNS myelin associated

semaphorins

CNS myelin associated chemorepellants function?

regulate axon regrowth following injury

semaphorins

cause growth cones to collapse and axon growth to cease to prevent extension of nearby axons

examples of nuerons that require dendiritic polarity?

retinal ganglion cells, cerebellar purkinje cells, pyrimidal neurons in cortex

what enforces polarity of neurons?

semaphorin 3A

how does semaphorin 3A work?

repels growing axons of cortical pyrimidal retinal ganglion and cerebellar purkinje neurons while attracting their dendrites

what does BDNF do?

promotes dendritic growth

what is dendritic tiling?

proper modulation of dendritic growth such that each dendritic arbour occupies appropriate space to accommodate incoming axons that will synapse on it

what are the 2 outcomes of dendritic tiling?

developing dendrites are regulated so they don’t grow toward nearby dendrites from same neuron

developing dendrites from dif nurons are repelled from one another to a greater or lesser degree to allow for adequate “coverage” of neuronal space

dual repulsion

each neuron much respond to molecular signals to prevent dendrites of the same neuron growing on top of each other

each neuron must respond to cues that restrict territories of dendritic arbors from neighboring neurons

chemoaffinity hypothesis

chemical identification tag that causes growing terminals to seek out specific location to form topographic maps

what causes topography in the retina?

a gradient of Eph

what influences recognition of postsynaptic positions?

ephrins, Ca2+ independent CAMs, and cadherins

events that occur for synaptogenesis?

molecules help growth cones recognize where to synapse

pre and post synaptic modification to allow for synaptic communication

adhesion molecules link pre and post synaptic domains

main molecule that initiates synaptogenesis?

neuregulin (Nrg1)

what does Nrg1 do?

causes increased synthesis and insertion of neurotransmitter receptors at postsynaptic sites

two families of adhesion molecules that are important for synaptogenesis?

neuroxins and neuroligins

where are neurexins found?

in the presynaptic membrane

where are neuroligins found?

postsynaptic membrane

what special function do neurexins have?

localize synaptic vesicles, docking proteins, and fusion molecules

what do neuroligins do?

interact with specialized postsynaptic proteins to promote clustering of receptors and channels of the postsynaptic density as synapse matures

how are neighboring synapses sorted out?

ephrins and Eph receptors help specify, genes have multiple sites for alternative splicing and those genes are distributed in dif pre and post- synaptic sites

can a neuron synapse with itself?

no bc homophilic binding leads to repulsion

neurotrophic factors

regulate differentiation, growth, and survival in nearby cells

how do neurotrophic factor regulate axon growth?

neurons compete for resources and many undergo apoptosis without

trophic substances regulate?

size of neuronal population

tropic substances regulation?

formation of synaptic connections

what are the 3 main functions of trophic substances?

survival of a subset of neurons from a considerably larger population, formation and maintenance of appropriate numbers of connections, and the elaboration of axonal and dendritic branches to support these connections

main neurotrophins?

NGF, BDNF, neueotrophin 3, 4, and 5

what does NGF do?

supports the survival of sympathetic neurons

main functions of neurotrophins

neural process growth or retraction

synpase stabilization or elimination

cell survival or death

what causes the selective actions of neurotrphins?

interactios with TrK receptors and p75 receptor - expression of particular receptor or subtype causes distinct responses

Hebb’s postulate

coordinated activity between pre and post synaptic neuron streenghtens synapse

what accounts for postnatal brain growth?

parallel growth of dendritic and axonal branches and addirtion of synaptic connections early in life

why does the brain continue to grow during the elimination phase?

continued elaboration of thesynapses that remain and their targets

critical periods

the time when experience and the neural activity that reflects that experience have a maximal effect on the acquisition or skilled execution of a particular behaviour

examples of behaviors that form during critical periods?

parental imprinting

basic properties of critical periods

encompasses the time during which a given behavior is es[ecially succeptical to envi infleucnes

envi influence elicitis neural activity in relevant sensory or motor pathway

nature of the activity (freq, amplitude, during, and correlation) drives changes in synaptic connections

oscillations

waves of electrical activity that are initially below threshold for AP generation that are essental in shaping cirucit networks so hey are prepared for optimal experience driven activity

how does segregation of left and right eye occur in LGN?

waves of electrical activity between bipolar and retinal cells that cause asynchronous firing from both eyes, leading to hebbian plasticity between axons

whats the difference between strabismus during development vs as an adult?

strabismus during development causes the deprived eye to be functionally disconnected from the visual cortex, leading to the other eye to take over ocular dominance

not much change if it occurs as an adult

how do axons compete for space?

if there’s unequal firing of one set of axons, it gains a competetive advantage and replaced many of the synaptics inputs of the axon that isnt firing

amblyopia

loss of acuity, diminshed stereopsis, and problems with fusion that arise fro early dificinencies of visual experience

esteropia

crossed eyes (convergent strabismus)

exotopia

wall eyes (divergent strabismus)

what do lower motor neurons do?

send axons directly to skeletal muscles

recieve info from sensory axons and recieve input from upper motor neurons

where are the cell bodies of lower motor neurons located?

in the ventral horn of the spinal cord and the motor nuclei of the cranial nerves in the brainstem

where are the cell bodies of the upper motor neurons located?

brainstem centres

what do upper motor neurons do?

initiate and guide voluntary and involuntary movments

what are the 4 neural centers responsible for movement?

gray matter of spinal cord and tegmentum of brainstem

upper motor neurons

cerebellum

basal ganglia

what are the relevant cells in the gray matter of spinal cord and tegmentum of brainstem?

lower motor neurons and local circuit neurons

what do the lower motor neurons do?

send axons out of brainstem and spinal cord to innervate skeletal muslces of head and body

what do local circuit neurons do?

major source of synaptic input to all lower motor neurons

what do upper motor neurons pathways do?

initiation of voluntary movements and for complex spatiotemporal sequences of skilled movements

what are important locations of descending upper motor neurons?

primary motor cortex and premotor cortex

what do upper motor neurons originating in the brainstem do?

regulating muscle tone and for orienting eyes, head, and body with respect to vestibular, somatic, auditory, and visual sensory info

how does the cerebellum function?

efferent pathways to the upper motor neurons to detect and attenuate the difference between an intended movement and the actual movement

how does the basal ganglia function?

prevent upper motor neurons from initiating unwanted movements and prepare the motor circuits for the initiation of movements

motor neuron pool?

all the motor neurons innervating a single muscle

how are motor neuron pools arranged in the spinal cord?

topographically in a medial-lateral way

which lower motor neurons in the spinal cord do medial circuit neurons project to?

lower motor neurons in the medial ventral horn

what do medial local circuit neurons do?

coordination of movements of upper and lower limbs + posture + billateral coordination of movements

what do lateral local circuit neurons do?

shorter axons that are predominantly ipsilateral for finer control of mvoements

what are the two types of lower motor neurons?

alpha motor neurons and gamma motor neurons

alpha motor neurons

larger, innervate striated muscle fibers that generate force needed for movement

gamma motor neurons

innervate muscle spindles that are sensory receptors in parallel with striated muscle fibers

muscle spindles

intrafusal muscle fibers that send info to spinal cord and brainstem abt length of muscle

function of gamma motor neurons

regulate sensory input by setting intrafusal muscle fibers to appropriate length

how many alpha motor neurons innervate a skeletal muscle fiber?

1

why wont damage to an alpha motor neuron cause significant damage?

because motor axons will synapse on extrafusal fibers on muscle

motor unit

single alpha motor neuron and its associated muscle fibers

slow motor units

smaller motor units with small “red” muscle fibres

what are slow motor units imortant for?

activities that require sustained muscular contraction like maintaining posture

fast ftigable motor units

larger alpha motor neuron that generate more force but have less mitochondria

fast fatiguable motor units function

brief exertions that require large forces like running or jumping

fast fatigue resistant motor units

intermediate size and are not as fast as FF motor units, are resistant to fatigue, and generate 2x as much force as slow motor unit

what kind of threshold do small, slow motor units have?

lower thresholds so are tonically active

how abt thresholds of fast motor units?

much hgher

what causes the gradual increase in muscle tension?

recruitment of motor units in a fixed order according to size

what is the size principle?

as synaptic input to the motor pool increases, progressively ;arger motor units that generate larger forces are recruited

fused tetanus

tension produced in individual motor units no longer has peaks and troughs that corrospond to the individual twitches evoked by the motor neuron’s action potentials

what are the two classes of intrafusal fibers

nuclear bag fibres and nuclear chain fibres

what do the two classes differ in?

arragenemtn fo nuclei

intrinsic architecture of myofibrils

dynamic sensitivity to touch

what are group 1a sensory afferents responsive to?

respond physically to small stretches bc they are dominated by signals transduced by dynamic subtype of nuclear bag fibers who are sensitive to velocity of fiber stretch