lec 12 synapse elimination and critical periods

Not all cells that are born in the nervous system survive and not all synapses that are initially formed during development are _________

maintained

Some synapses are maintained while others are eliminated- this is related directly through the activity of these synapses through sensory or motor experiences "___ __ __ ____ __"

use it or lose it

in what ways do axonal projections become refined from development to adulthood

axons can become refined through three refinement properties which are

Topography, convergence, and postsynaptic compartment

refinement of topography- individual axons spread out further in early development in their topographical zone therefore some of these branches are ________ in refinement

eliminated

refinement of convergence- a single neuron will receive more presynaptic inputs during development than will remain in adulthood

less presynaptic inputs in adulthood

Refinement of postsynaptic compartment
there is refinement of synaptic connections on specific regions of the neuron

a neuron that comes in and blankets the postsynaptic cell, needs to prune back so that it is only in one particular part of the cell

How can convergence be quantified?

by measuring the postsynaptic potential (PSP) amplitude or examining structural changes

if a target cell has afferent input from three different neurons. Stimulating one afferent neuron evokes PSP of a given amplitude But stimulating 2 or 3 afferent neurons result in PSP doing what to the amplitudes?

increasing

convergence on adult cells ________ over time which indicates what?

decreases because some synaptic inputs are eliminated over time

synapse elimination is widespread and occurs in most cases but may occur to what degree & region?

different degree in different brain regions or cell types

what's the issue with counting PSP amplitude?

some systems receive hundreds or thousands of presynaptic contact

Synapse elimination can be studied indirectly by examining the degree of

axon arborization over time

The elimination of axon projection is a common phenomenon in many different regions of the nervous system. Seemly bizarre transient projections arise an example is that in rats the visual cortex sends projection to the spinal cord in the first postnatal week.
These projections were _________ by the second week

eliminated

collateral neurons

An axon typically develops side branches called axon collaterals, so that one neuron can send information to several others. These collaterals, just like the roots of a tree, split into smaller extensions called terminal branches. Each of these has a synaptic terminal on the tip.

Consider the development of the visual system. How do projections become refined over time?

arborizations are refined by RCG from one eye form transient collaterals into inappropriate layers of LGN which are then lost leading to arborization to be located in correct layer/
refinement of innervation happens when there is multiple axon terminals for control of the NMJ and one axon eventually wins out while others retract

a mature NMJ single muscle fiber is innervated by how many motor axon terminals?

one

What are ocular dominance columns?

Ocular dominance columns are specialized structures within the visual cortex that organize neural responses based on input from each eye. They are essential for processing binocular visual information and are subject to modification of sensory experiences during development

What inappropriate projection are transiently established?

During innervation of the LGN in embryonic development, RGC from one eye form transient collaterals into the inappropriate larger of the LGN. Later these collaterals are lost and all arborization are located in the correct layer

describe the experiments that were performed to asses the refinement of projections in the visual system over time

Wiesel & Hubel manipulated the visual input to one or both eyes of cats during early development.

-light evoked activity was prevented by suturing one of the cat's eyelids close during birth to induce monocular deprivation

-after the eyelid was open, majority of cortical neurons in all layers no longer responded to stimulation of the eye

- Different experiment shut both eyes and results showed that most cortical neurons remained responsive to stimuli from both eyes but total number of light-responsive cortical neurons were decreased

-The conclusion to both experiments was that the total amount of evoked activity does not necessarily determine the strength of a visual pathway but the difference in activity determines strength of the projection known as the competition hypothesis

explain how visual deprivation or strabismus during development can influence ocular dominance in adulthood

strabismus the visual cortex showed that majority of neurons responded to stimulation of one eye or the other but not both meaning that neurons were mostly monocular.
In conclusion synapses from each eye must be active at same instant to keep strong functional contacts with same neurons

what is strabismus?

the misalignment of the eyes so that the visual stimuli activate different positions on both retinas

The neuromuscular junction (NMJ) is polyneuronally innervated at birth but all but one axon are eliminated over the first _______ postnatal weeks (#?)

two

____ _____________ and other colleagues provided strong evidence that this competition of nerve terminals for control of individual muscle fibers is activity-dependent

Wes Thompson

describe the experiments that first demonstrated activity-dependent synapse elimination at the NMJ

Thompson blocked nerve transmission with tetrodotoxin (TTX) at the NMJ in a rate during normal period of synapse elimination
-several muscle fibers remained polyneruonally innervated, suggesting that competition occurs via activity pattern
-electronic stimulation of muscle fiber was shown to speed up at synapse elimination
-This suggest postsynaptic electrical activity influences the competition of individual motor axon

further experiments demonstrated that a synapse can only influence its neighbors if they are located within a

short physical distance

to demonstrate that synapses can only influence neighbors in short distances two motor axons were positioned on the same muscle fiber and intracellular recordings were made from muscle to monitor polyneuronal innervation
If synapses from the two axons were established close together, synaptic elimination occurs within

a few weeks

If synapses are farther than 1-2mm, synaptic elimination would

fail to occur

How can sensory coding in the brain be altered experimentally?

in early development mice were treated to high frequency clicks which widened their tuning curve in development and synchronously activated a population of cochlear neurons

the coding properties of a neuron refer to the response of a neuron to

specific ranges of stimuli

an example of sensory coding properties is neurons in the visual cortex respond to

vertical vs horizontal movement

What is a critical period?

limited periods in development during which neural systems are particularly plastic

the first solid evidence of critical periods was observed in

visually impaired cats

A critical period is most important in what stages of develpoment?

early stages

Take an a sensory pathay like visual for example. If a young mice at early stage of development is deprived of vision in one eye then what happens to their ocular dominance?
(in mouse eyes theres a bias in ocular dominance called ipsilateral eye)

it shifts toward the other eye

If an adult mice at late stage of development is deprived of vision in one eye, what happens to their oculuar dominance and why?

no change because they are past the critical period

what kind of signaling can be lost for there to be ocular dominance shift in late development?

GABA/GAD65

What mechanisms underlie critical periods?

critical period can be brought forward by enhancing GABA and promoting rapid maturation of interneurons through BDNF expression