Synaptic plasticity Flashcards
Describe the memory types.
**hint: explicit and implicit
EXPLICIT (Declarative)-
- Facts
- Events
IMPLICIT (Non-declarative)
- Procedural memory- skills and habits (Striatum)
- Classical conditioning- subdivided into emotion responses (Amygdala) and Skeletal musculature (Cerebellum)
What is learning?
The response of the brain to environmental events and involves adaptive changes in synaptic connectivity, which will, in turn, alter behavior.
What is Hebb’s rule?
Persistence/repetition of a reverberating activity leads to the induction of lasting cellular changes that add to its stability
Axon A near enough to excite cell B and repeatedly takes part in firing it
Growth process/metabolic change occurs in both cells
Such that A’s efficiency, as one of the cells firing B, increases
What are the two rules of synaptic modification?
- Neurons that fire together, wire together
- Neurons that fire out of sync lose their link
Strengthening/weakening synaptic connections in brain provides means which learning occurs and memories are formed
Explain the example of sight and smell of roses as an example of learning.
Cell A: Sensory input of sight of rose
Cell B: Sensory input of cells of smell of rose
Cell C: Sensory input of smell of onion
Their individual firing is insuffiecient to create a EPSP.
Cell A and Cell B spontaneously fire in sync, repeatedly = SUMMATION.
Sight of rose becomes associated with smell off rose, not onion
What is long-term potentiation
Mechanism underlying synaptic strengthening based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons.
The opposite of LTP is long-term depression, which produces a long-lasting decrease in synaptic strength.
What does electrophysiology tell us about long-term potentiation?
How is LTP observed in other brain areas?
Electrophysiology allows easy analysis of hippocampus shape and anatomy of pathways
Temporal:
Summation of inputs reaches a stimulus threshold –> induction of LTP e.g. repetitive stimulation
Associative:
Simultaneous stimulation of a strong and weak pathway will induce LTP at both pathways (spatial summation) “cells that fire together, wire together”
Specific:
LTP at 1 synapse is not propagated to adjacent synapses. INPUT SPECIFIC
What happens at a synapse at rest?
Glutamate released at membrane potential.
NMDA receptor blocked by Mg2+
AMPA receptor activated to create EPSP by Na+ influx. Depolarisation here insufficient to expel Mg2+
What happens at a synapse during depolarisation?
Glutamate released onto an active cell (depolarised membrane)
At NMDA receptor, Mg2+ blockade relieved, Ca2+ enters
AMPA receptor. activated
Na+ passes through NMDA and AMPA receptor into Post-SN
Ca2+ entry through NMDA receptor leads to activation of:
Protein kinase C
CamKII (Ca2+ calmodulin-dependent protein kinase 2)- a MOLECULAR SWITCH
Describe the action of CamKII
State what happens before and after CamKII activation
It is a molecular switch
It has autocatalytic activity- becomes phosphorylated (active) and then no longer needs Ca2+
It functions to phosphorylate existing AMPA receptors which increases its effectivity.
Stimulates the insertion of new AMPA receptors into the membrane.
After stimulus has been removed, CamKII maintains phosphate insertion on AMPA. This maintains excitability of neurons for minutes/hours (LTP)
Before the activation: Few AMPA receptors, small EPSP
After activation: More AMPA receptors working more effectively. Larger EPSPs and LTP
Outline the presynaptic event in LTP
Ca2+ enters NMDA receptor into cell
Activates NO synthase which converts arginine into NO
NO diffuses from postsynatpic cell into pre-synaptic cell
It activates guanylyl cyclase
Which produces cGMP (2nd messenger)
Signal transduction cascade leads to increased glutamate release from synaptic bouton
Define and describe the role of PSIs in late phase LTP
Protein synthesis inhibitors (PSI) prevent the consolidation of long-term memories and LTP
Acquisition (training)
******
Consolidation
Recall (testing)
*PSIs injected just post-acquisition inhibits recall necessary for consolidation
CREB (cAMP response element binding protein) activated by phosphorylation by a number of kinases (Pka, CamKII)
State the duration and mechanism involved in early phase LTP
Minute-hour
Ca2+–> NMDA receptor and subsequent enhancement ans AMPA receptor efficiency, NO
State the duration and mechanism involved in late phase LTP
Hours/ days/months
Requires new protein synthesis (may include morphological changes and establishment of new synapses)
Ca2+ activated signal transduction cascades
- Activates new protein synthesis from dendritically localized mRNAs
- filter back to cell body to stimulate CREB-mediated gene transcription, protein synthesis and recruitment of new protein to the synapse
What is LTD?
How is it different and similar to LTP?
How does LTP and LTD reflect bidirectional regulation?
LTP created by increased frequency stimulation. Long term depression created by decreased frequency stimulation and instead of increase in EPSP, you get a decrease
Similarities:
- NMDA dependent
- AMPA receptors (are dephosphorylated and removed from)
Differences:
Prolonged low-level rise in Ca2+ activates phosphatases rather than kinases (causing removal of Ca2+)
LTP and LTP reflect bidirectional regulation of phosphorylation and a number of postsynaptic AMPA receptors.
