T1 L19 Synaptic plasticity in learning & memory Flashcards
What are the 2 types of memory?
Explicit
Implicit
What is explicit memory?
Declarative memory
Facts & events
Medial temporal lobe & diencephalon
What is implicit memory?
Nondeclarative memory
Procedural memory: skills & habitats
Classical conditioning - skeletal musculature & emotional responses
What is the definition of learning?
Response of the brain to environmental events & involves adaptive changes in synaptic connectivity which alter behaviour
What is Hebb’s rule?
Persistence or repetition of reverberatory activity tends to induce lasting cellular changes that add to its stability.
When an axon of cell A is near enough to excite a cell B & repeatedly or persistently takes part in firing it, some growth processes or metabolic changes takes place in one or both cells so A’s efficiency is increased
Describe the process of learning behaviour
1) External stimulus
2) Activation of cell assembly by a stimulus
3) Reverberating activity continues after activation after stimulus is removed
4) Hebbian modification strengthens reciprocal connections between neutrons that are active at the same time
5) Strengthened connections of the cell assembly contain the engram for the stimulus
6) After learning, partial activation of the assembly leads to activation of the entire representation of the stimulus
What are the rules of synaptic modification?
Cells that wire together fire together
Neurons that fire out of sync lose their link
Strengthening & weakening synaptic connections in the brain provides a means by which learning occurs & memories can be formd
What is long term potentiation?
Mechanism underlying synaptic strengthening
Where do you record high frequency electrical stimulation from?
The cells within the dentate gyrus
How long is the long term potentiation produced by 1 high frequency stimulation?
Hours
How long is the long term potential produced by multiple high frequency stimulations?
Days/months
What is the definition of temporal in respect to LTP?
Summation of inputs reaches a stimulus threshold that leads to induction of LTP
What is the definition of associative?
Simultaneous stimulation of a strong & weak pathway will induce LTP at both pathways (spatial summation)
Coincidence detection
Why are long term potentiation specific?
LTP at 1 synapse is not propagated to adjacent synapses (input specific)
What happens at the synapse?
1) Glutamate released onto inactive cell
2) AMPA receptor activated to produce EPSP
3) NMDA receptor blocked by Mg2+. Depolarisation is not sufficient to expel Mg2+
4) Glutamate released onto active cell
5) AMPA receptor activated
6) Mg2+ block on NMDA is relieved
7) Na+ moves through AMPA & NMDA channel
8) Ca2+ through NMDA channel
9) Activation of PKC & CaMKII
10) Phosphorylation of existing AMPA receptors which increases their effectiveness. Stimulates insertion of new AMPA receptors into the membrane
Describe CaMKII molecular switch
Ca2+ entry through NMDA receptor leads to activation of CaMKII
CaMKII has autocatalytic activity & becomes phosphorylated
Once phosphorylated it no longer requires Ca2+
Maintains phosphorylation after depolarising stimulus has receded
Maintains increased excitability of neurons for minutes to hours
How is nitric oxide synthase activated?
By Calcium diffusing through NMDA channel
What happens once nitric oxide synthase is activated?
NO diffuses from site of production
Activates guanylyl cyclase in presynaptic terminal
Guanylyl cyclase produces second messenger cGMP
Signal transduction cascade leads to increased glutamate release from the synaptic buton
What is required for long lasting LTP?
Protein synthesis
What are the stages of memory formation?
Acquisition - training
Consolidation
Recall - testing
What is the consequence of injecting a protein synthesis inhibitor just post-acquisition?
Inhibits recall which is necessary for consolidation
What is CREB & how is it activated?
cAMP response element
Binding protein activated by phosphorylation by a number of kinases
Describe early phase LTP
Lasts minutes to hours
Explained by Ca2+ actions through NMDA receptor & subsequent enhancement of AMPA receptor efficiency, presynaptic events etc.
Describe late phase LTP
Lasts hours/days/months
Requires new protein synthesis & can involve morphological changes & establishment of new synapses
Describe the calcium activated signal transduction cascades involved in LTP
Activate new protein synthesis from dendritically localised mRNAs
Filter back to cell body to stimulate new gene transcription, protein synthesis & recruitment of new proteins to the synapse
What is long term depression?
Activity dependent reduction if efficacy of neuronal synapses
Opposite of long term potentiation
What does low frequency stimulation cause?
Decrease in EPSP amplitude on further stimulation
What is involved long term depression?
NMDA dependent process
AMPA receptors are de-phosphorylated & removed from the membrane
Prolonged low level rises in Ca2+ activate phosphases instead of kinases
What do LTP & LTD reflect?
Bidirectional regulation of
1) phosphorylation
2) number of postsynaptic AMPA receptors
What is AP5 and what does it do?
NMDA receptor antagonist
Blocks hippocampal LTP
Blocks learning in the Morris Water Maze
What is the effect of alcohol on learning and memory?
NMDA receptor antagonist
Directly blocking normal LTP processes leads to blackouts & amnesia
Disrupts hippocampal theta rhythms & short term memory
What are the consequences of chronic alcoholism associated with nutritional deficiency?
Can result in Korsakoff’s syndrome or psychosis
Loss of recent memory & tendency to fabricate accounts of recent events (confabulation)
What is the effect of benzodiazepines on learning & memory?
Indirect agonist of GABA(A) receptors. Binding increases receptor affinity for GABA, increase frequency of channel opening
Anxiolytic & hypnotic drugs
What is a side effect of benzodiazepines?
Anterograde amnesia
What is the effect of cholinergic / anticholinergics on learning & memory
Acetylcholine projections
Basal forebrain bundle: medial septum to hippocampus. Basal nucleus to cortex
Septum to hippocampus projection regulates theta waves
Scopolamine (muscarinic receptor antagonist) suppresses theta waves & impairs spatial learning
What can be given to treat Alzheimers?
Acetylcholinesterase inhibitors e.g. physostigmine
Boost cholinergic function & improve memory impairments
Give some other learning processes which use LTP or a similar mechanism
Activity-dependent synaptogenesis
Motor learning e.g. riding a bike
