BIOL 2480 - Plasticity

Hebbian synapse

•"Neurons that fire together wire together"

Hebbian synapse, Aka Coordinated firing activity will

strengthen synaptic connections

Hebbian synapse is an Example of

activity-dependent plasticity

Hebbian synapse is a key

aspect of learning and memory

Plasticity in the neural context just means firing (or morphology) changes with

stimuli

Those presynaptic neurons that match the postsynaptic pattern will increase

connectivity

activity-dependent plasticity is a change in firing based off

activity

If presynaptic neurons don't match the postsynaptic pattern, causes a loss of

synapses

After birth your brain grows but you mostly don't add

new neurons

•After birth your brain grows but you mostly don't add new neurons, this an example of

hypertrophy

Huge increase in ____ after birth

synaptogenesis

Huge increase in synaptogenesis after birth, followed by

stabilization and decline

Astrocytes stabilize

synaptic connections

Microglia clean up

old synaptic sites

In postnatal humans most increases in brain size are due to changes in connections, and maybe increases in

cell size (hypertrophy),

In postnatal humans most increases in brain size are due to changes in connections, and maybe increases in cell size (hypertrophy), but not due to increased

cell number (hyperplasia)

Astrocyte processes surround the synaptic cleft to

stabilize connection

Astrocyte processes surround the synaptic cleft to stabilize connection. Also uptake neurotrans to reduce

excitotoxicity,

Astrocyte processes surround the synaptic cleft to stabilize connection. Also uptake neurotrans to reduce excitotoxicity, and also secrete ECM proteins to help

stabilize connections

Astrocytes can also play a role in

calcium signaling

Connection is very

dynamic so can aid in plasticity

Astrocytes Can also actively secrete glutamate and other neurotransmitters to regulate

synaptic activity

Individual sensory circuits can change

synaptic connectivity based on activity

Ex1: mammalian visual system, eye dominance can affect

topographic maps

Remember: each location on the retina has corresponding location in the

optic tectum

Each eye has both

•ipsilateral and contralateral innervation

Block one eye and other one takes over its

space in tectum

In auditory system, prolonged exposure to specific sounds can affect

tonotopic maps

The ear does not have topographic organization because of

•how sound enters ear

Ear does have TONOTOPIC organization, meaning

different frequencies (tones) stimulate different areas

This tonotopy is passed along to

cortex.

More exposure to a given tone means more

•connections to that area of cortex.

In mammals, peripheral touch receptors map onto

•somatosensory cortex

Higher receptor density correlates to more

•neurons on cortex

Rats have a

barrel cortex

Rats have a "barrel cortex" that maps directly onto

facial whiskers

Repeated stimulation of 1 whisker can increase

cortical representation

Repeated stimulation of 1 whisker can increase cortical representation of the cortical neuron in the

somatosensory map

Sensory plasticity - touch, can change

throughout life

A critical period is the developmental timeframe over which

neural circuits are most sensitive to a given environmental stimulus

Exposure during the critical period can influence

synaptic connectivity.

Baby birds imprint on the first object they see shortly after hatching. Information is stored in

association cortical regions

Baby birds imprint on the first object they see shortly after hatching. Information is stored in association cortical regions and results in increased

•NMDA activation but must happen early

Sensorimotor skills and complex behaviours learning is more

plastic, less hardwired

association cortical regions, are regions associated with

primary cortical complex

Retinal ganglion cell axons form the

•optic nerve.

Optic nerve goes to

lateral geniculate nucleus (LGN)

LGN goes to

visual cortex

Cortex is layered structure and layer 4 has

ocular dominance columns

Cortex is layered structure and layer 4 has ocular dominance columns with inputs from

one eye or the other

Layer 4 of visual cortex has alternating eye-specific domains called

ocular dominance columns

See alternating bands of synaptic terminals from

right eye and left eye

Figure shows labelling experiment where you inject a dye into one eye and track its innervation through to

layer 4 of the cortex

Figure shows labelling experiment where you inject a dye into one eye and track its innervation through to layer 4 of the cortex. Shows up as alternating bands in bottom figure.

Good set of experiments to test

ocular dominance after deprivation

During normal development, there is equal distribution of

•ipsilateral and contralateral neurons in layer 4

Close one eye early in development and then reopen it and you completely lose

contralateral signalling

•No effect if same experiment done in adults, showing that

Critical period is during

first 2 months of life

an eye was closed at birth and kept closed for 2.5 months. Eye was opened and then cat tested at 38 months of age. Despite eye being opened for almost 36 months, you have lost

all contralateral representation and only have group 7 cells being active

same type of experiment was done but this time in an adult cat. Eye was closed at 12 months and kept closed until 38 months before being reopened and tested. Overall activity was

lower, showing synaptic loss, but still had normal distribution, showing critical period for ocular dominance development

In normal visual systems, afferents from each eye, and LGN, compete for

•space in cortex

During deprivation, synapses from the eyed side grow over into the

ocular dominance columns of the uneyed side

Bottom graph shows the distribution of dendritic arbors in the visual cortex. First bar is the control situation. Second bar is what happens in you close one eye; the neurons in cortex responsible for receiving inputs from that eye have

fewer spines in the arbor, allowing spines from the other afferents to grow over to take up this space.

Critical periods are defined by an

excitatory/inhibitory balance

Sustained glutaminergic inputs modify

•calcium channels, cytoskeleton, cell adhesion, and transcription

GABAergic interneurons can regulate

excitability of cortical neurons

GABAergic stimulation and transcriptional activation decreases at

end of critical period

Activity of GABA, various transcription factors and BDNF determine how long a synapse stays

plastic

Once that activity stops or slows, the synapse can no

longer change.

factors that influence excitability of cortical neurons during critical period.

BDNF is also upregulated during critical period from

cortical neuron, which influences the synaptic connections of GABAergics

an excitatory/inhibitory balance helps stabilize

connections, if balance is interrupted, so are connections

Sustained glutaminergic inputs modify calcium channels, opening them for

longer

Sustained glutaminergic inputs modify cytoskeleton, increasing

connections

Sustained glutaminergic inputs modify transcription, in nucleus, adds more

receptors and kinases

After critical period, turns off because

molecular triggers stop

•Remember, rat whiskers have a topographic map in the somatosensory cortex

Disrupt one row of whiskers and the remaining afferents take up

missing space in cortex

The trigeminal nerve goes from whisker to

barrel cortex

Completely cut the nerve and entire topographic representation is

lost

Completely cut the nerve and entire topographic representation is lost so it is

activity-dependent

Size of barrel cortical areas are regulated by overall activity at the level of

neurotransmitter receptor.

Disrupt glutamate receptors and decrease

barrel area

Neuromodulators are critical for

barrel organization.

Serotonin mediates activity so blocking serotonergic innervation acts like a

nerve cut.

Neuromodulators are just any substance that changes/regulates

neural activity

serotonergic responsible for

spike broadening

Molecular mechanisms of plasticity: 1) presynaptic activation releases

glutamate

Molecular mechanisms of plasticity: 2) Glutamate binds AMPA and NMDA to

excite cell AND bring in Ca2+

Molecular mechanisms of plasticity: 3) Ca2+ acts on cytoskeleton to

stabilize connection

Molecular mechanisms of plasticity: 4) Continued Ca2+ activates more

voltage-gated Ca2+ channels

Molecular mechanisms of plasticity: 5) Ca2+ activates transcription of

BDNF to strengthen synapse

Molecular mechanisms of plasticity: 6) Glutamate also binds to

mGluR to activate translation

Sustained activation leads to more

Ca2+ entry

Ca2+ levels can regulate kinase pathways to allow

•long-term potentiation (LTP) and long-term depression (LTD)

Kinases also interact with

CREB for transcription

Kinase pathways can also feed back onto receptors to make them more

responsive to stimulation

Localized changes can directly affect

dendritic arbor

Increased Ca2+ activates

cytoskeleton to increase arborization

Increased Ca2+ can release

calcium from ER

Increased Ca2+ can allow translation into

proteins for more receptors