Adult Cortical Plasticity

1. Maps in somatic sensory and motor cortex

2. Reorganization of cortical maps following sensory deprivation

3. Synaptic basis of cortical plasticity

---LTP and LTD

---Hebb’s hypothesis revisited

4. Relationship between developmental and adult plasticity

Properties of Cortical Maps

1. Topographically ordered: Nearby points in periphery are represented by nearby cortical neurons.

2. Multiple Representations: The same set of sensory or motor information are represented repeately by multiple cortical areas.

3. Distorted mapping: Periphery points that required higher spatial resolution are represented with disproportional cortial areas (larger number of cortical neurons).

Map of body surface in the somatic sensory cortex

MAP OF BODY SURFACE IN THE MOTOR CORTEXMAP OF BODY SURFACE IN THE MOTOR CORTEX

Plasticity of rat somatosensory cortex Plasticity of rat somatosensory cortex

Barrel Cortex – receiving sensory inputs from whiskersBarrel Cortex – receiving sensory inputs from whiskersDepriving sensory inputs by removing whisker – shrinkage of Depriving sensory inputs by removing whisker – shrinkage of corresponding barrelscorresponding barrels-- Importance of normal sensory inputs even in adult-- Importance of normal sensory inputs even in adult-- Activity-dependent competition exists in adult cortex-- Activity-dependent competition exists in adult cortex

Barrel cortex

Functional changes in V1 due to scotoma (blind spot)Functional changes in V1 due to scotoma (blind spot)

Visual field is represented by the grid on the retina, with corresponding maps shown on V1. Lesion of retina first silenced the corresponding cortical area, but reorganization of the receptive fields of cortical neurons leads to increased representation of the areas around the lesion and reduced representation of the lesioned area. (Gilbert and Wiesel)

Artificial scotoma – Deprivation of visual input to specific region of retina without lesion results in similar reorganization of the cortical receptive fields.

Functional expansion of cortical representation by repetitive use

Monkey was trained in a task that required heavy usage of digits 2,3,4

--expansion of cortical representation of these digits after a few months

Functional changes in the somatic sensory cortex of an owl monkey following amputation of a digit.Functional changes in the somatic sensory cortex of an owl monkey following amputation of a digit.

Question remains to be answered: Are functional changes due to structural changes in the connectivity between neurons, or simply Question remains to be answered: Are functional changes due to structural changes in the connectivity between neurons, or simply

silencing of synaptic transmission, e.g., long-term depression or increased inhibition? silencing of synaptic transmission, e.g., long-term depression or increased inhibition?

Functional brain imaging studies showing larger cortical representation of left figures for string player who has an earlier inception of practice, although string players in general have higher representation than non-string players (controls) in the same orchestra.

Evidence from human studies

Use-dependent changes in synaptic functionsUse-dependent changes in synaptic functions

Short-term plasticity: synaptic facilitation, synaptic fatigue, Short-term plasticity: synaptic facilitation, synaptic fatigue, post-tetanic potentiation (PTP) post-tetanic potentiation (PTP)

Facilitation (10s msec):

Increased transmitter release due to residue Ca2+ of previous stimuli

Fatigue (100s msec): Depletion of synaptic vesicle supplydue to high-frequency use

Post-tetanic potentiation (minutes):

Increase mobilization of vesicle supply due to Ca2+ accumulation induced by tetanus

(Found to different degrees at all synapses)

Use-dependent changes in synaptic functionsUse-dependent changes in synaptic functionsLong-term potentiation (LTP) and Long-term depression (LTD)Long-term potentiation (LTP) and Long-term depression (LTD)

-- Persistent increase or decrease in synaptic response due to -- Persistent increase or decrease in synaptic response due to repetitive activity, found in hippocampus and cortexrepetitive activity, found in hippocampus and cortex

-- Brief high-frequency stimulation – LTP-- Brief high-frequency stimulation – LTP

Prolonged low-frequency stimulation – LTDProlonged low-frequency stimulation – LTD

MechanismMechanism::

1.1. Induction of either LTP or LTD requires postsynaptic CaInduction of either LTP or LTD requires postsynaptic Ca2+2+ rise. rise.

2.2. At most synapses, activation of NMDA receptors is required for At most synapses, activation of NMDA receptors is required for

the induction of LTP/LTD.the induction of LTP/LTD.

3. LTP/LTD at many synapses are due to increase/decrease of 3. LTP/LTD at many synapses are due to increase/decrease of postsynaptic AMPA-type glutamate receptors, but presynaptic postsynaptic AMPA-type glutamate receptors, but presynaptic increase/decrease of transmitter release may also occur. increase/decrease of transmitter release may also occur.

Developmental vs. adult plasticity

1. Are these two forms of plasticity depend on similar synaptic mechanisms?

Evidence:

-- Development of ocular dominance columns is prevented by blocking NMDA receptors. (M. Constantine-Paton)

-- Critical period plasticity (ocular dominance modification due to monocular deprivation) can be revived in adult primary visual cortex by protease treatment (that remove extracelluar matrix around neurons). (L. Mafei)

-- LTP/LTD can be induced in developing and adult cortex by similar stimulation.

-- LTP/LTD induction can result in structural changes at synapses, presumably also changes in connectivity

LTP – increase spine formation, swelling of existing spines

LTD – shrinkage and retraction of spines

2. Do learning and memory in adult brain involves processes similar to activity-dependent developmental refinement of connections?

Evidence:

-- LTP is required for spatial learning (hippocampus) and fearing conditioning (amygdala) in rats

-- LTP/LTD induction is accompanied by structural changes at synapses

-- Neruotrophins required for developmental refinement of connections (e.g., in ocular dominance segregation) is also required for LTP induction in adult brain. Neurotrophins

The key question:

Does activity-induced LTP and LTD leads to formation and elimination of synaptic connection?

(Does functional plasticity lead to structural plasticity? )