Long-term Potentiation, Long-term Depression, & Synaptic Plasticity Flashcards
Short-term vs. Long-term Memory & Implicit vs. Explicit Memory
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
Fragile X Syndrome
– 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
Alzheimers & Parkinson’s Disease
• 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
Hebb’s Postulate
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
Hebbian Hypothesis
– 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
Hippocampal Circuitry
– 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
Glutamate Receptors (AMPA vs. NMDA)
– 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
Clinical Relevance: NMDA Receptor
PCP (date rape drug) and alcohol bind to NMDA receptor and inhibit memory
Long-Term Potentiation
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
Ca-Calmodulin Dependent Kinase (CaMKII)
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
Specificity vs. Associativity
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
Long-Term Depression
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
LTP vs LTD
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
Plasticity Summary
– 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