Long-term Potentiation, Long-term Depression, & Synaptic Plasticity

Question 1

Short-term vs. Long-term Memory & Implicit vs. Explicit Memory

Answer 1

o Basal ganglia – site of implicit memory – procedural memory of skills and tasks
o Hippocampus – site of explicit memory – memory of facts and experiences and learning
 Medial temporal lobe
o Glutamate receptors (particularly NMDA) main player in memory formation

Question 2

Fragile X Syndrome

Answer 2

– most common single gene inherited form of mental retardation
o Abnormal X chromosome
o Defect at level of synaptic connectivity – different anatomically-shaped dendritic spines

Question 3

Alzheimers & Parkinson’s Disease

Answer 3

• Alzheimer’s Disease – extreme shrinkage of hippocampus and cerebral cortex
o Enlargement of the ventricles
• Parkinson’s Disease – basal ganglia is area that is dysfunctional

Question 4

Hebb’s Postulate

Answer 4

o When an axon of a cell A is near enough to excite a cell B and repeatedly and persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increase

Question 5

Hebbian Hypothesis

Answer 5

– neurons that fire together, wire together, and their connections are preserved
o LTP: Correlated pre- and post-synaptic activities cause synapse strengthening: stabilization
 Higher frequency of firing will lead to strengthened neural input
o LDP: Uncorrelated pre- and post-synaptic activities cause synapse weakening: elimination

Question 6

Hippocampal Circuitry

Answer 6

– made from THREE major synaptic contacts – mostly glutamatergic neurons
o Dentate gyrus (DG) – contain large amount of granule cells
 Input: Entorhinal cortex sends axons via performant pathway
 Output: send axons via mossy fiber pathway to CA3 region
o CA3 Region – triangular neurons
 Input: Dendate gyrus neurons send axons via mossy fiber pathway to CA3 region
 Output : Send axons via schaffer collateral pathway to CA1 region
o CA1 Region – triangular neurons
 Input: CA3 neurons send axons via schaffer collateral pathway
 Input: Entorihinal cortex sends axons via perforent pathway

Question 7

Glutamate Receptors (AMPA vs. NMDA)

Answer 7

– AMPA and NMDA – non-selective cation channels that are permeable to Na+, K+, and Ca+ leading to depolarization of the cell
o AMPA Receptor – activation causes permeability mostly to monovalent cations
 Fast activation AND fast INactivation
 Excitatory post-synaptic current (EPSC) peaks at a high value
 Only receptor that conducts current at resting potential
 Removing receptors are the basis of LTD
o NMDA Receptor – interspersed between AMPA receptors
 Activation and INactivation is slower
 Excitatory post-synaptic current (EPSC) can be recorded over a longer period of time and peaks at a lower value
 Only active if glutamate AND glycine binds AND receives the required AMPA receptor depolarization to remove the magnesium-block which will then allow calcium influx

Question 8

Clinical Relevance: NMDA Receptor

Answer 8

PCP (date rape drug) and alcohol bind to NMDA receptor and inhibit memory

Question 9

Long-Term Potentiation

Answer 9

o Induce high-frequency stimulation  tetany occurs  increase in amplitude of post-synaptic response over time
o Hebb’s hypothesis – when neurons fire together they wire together
o Requires depolarization via AMPA receptor to relieve Mg blockade of NMDA and Ca+ entry
o May require protein synthesis
o Epigenetic changes in chromatin structure may participate
o NMDA receptor antagonist – potentiation will NOT occur; long-term potentiation depends on NMDA receptors

Question 10

Ca-Calmodulin Dependent Kinase (CaMKII)

Answer 10

o Ca+ binds to calmodulin  Ca-calmodulin binds to enzyme to make it fully active  phosphorylates proteins
o Enzyme kinetics change with increase/decrease in Ca+
o Calcineurin – calcium sensitive phosphatase that removes phosphate groups from proteins

Question 11

Specificity vs. Associativity

Answer 11

o Specificity – if you stimulate one particular synapse, that synapse will be strengthened
o Associativity – even when there’s weak stimulation in the proximity of strong stimulation, the weak synapse will be strengthened as well

Question 12

Long-Term Depression

Answer 12

o LTD can counter-act LTP and vice-versa, even at the same synapses
o Frequency Dependent – decreasing firing frequency will cause synaptic efficacy to drop as a result of low amount of calcium influx
 Synaptic enhancement would occur when firing frequency was high
o Therefore LTD shows opposite effect of LTP

Question 13

LTP vs LTD

Answer 13

o LTP – brief high frequency stimulation; activation of NMDA receptors; large rise in Ca+; activates kinases; insertion of AMPA receptors; strength of expression is input specific
o LTD – low frequency stimulation (10-15 min); activation of NMDA receptors; small rise in Ca+; activates phosphatases; removal of AMPA receptors

Question 14

Plasticity Summary

Answer 14

– capacity to undergo a change in structure and function
o Control of synaptic plasticity by NMDA receptors
 Central role of Ca+ in initiation of long-term plastic changes
 NMDA receptor is also a “scaffold”
o Adapts to changing needs and activity levels
o Short-term modulation (sec – min) – mechanisms are presynaptic
o Long-term plasticity (min – years)
 Mechanisms are both pre and post-synaptic; LTP; LTD; frequency dependent
o Early in development, brains are highly plastic and are shaped a lot by experience
o Later in development/life, plasticity decreases
o Most clearly seen in language acquisition – exposure to a language must take place during a certain critical period to facilitate fluency
 Attainment of fluency is best in the critical period and will decrease with age