Synaptic plasticity in learning and memory Flashcards
What is the explicit memory?
Facts
Events
What is the implicit memory?
Procedural memory of skills and habits
Classical conditioning - Skeletal musculature and Emotional response
Define learning
The response of the brain to environmental events and involves adaptive changes in synaptic connectivity which will in turn alter behaviour.
What is meant by wiring?
The way in which our neurons are connected by snaptic connections
These are plastic and malleable so can be changed
What did hebb say about learning and memory?
Cell assembly - neurons connected by reciprocal connections between neurons
External stimulus causes activation of the cell assembly
If activation of the cell assembly occurs for long enough consolidation occurs by a growth process and the reciprocal connections are made more effective. The neurons become wired together - permanent modification of the cell assembly.
If only part of the cell assembly is activated later, the strengthened connections could cause the whole assembly to become activated. The entire stimulus may be recognized from just part of it
What rules of synaptic modification exist?
Neurons that fire together wire together
Neurons that fire out of sync lose their link
How are learning and memories formed?
Strengthening and weakening of synaptic connections
Give the effect of stimulation of an individual hippocampal neuron before and after learning
May not be enough to crease an EPSP great enough to fire an action potential before learning but after repetition it will elicit an action potential
What is long term potentiation (LP)?
Mechanism underlying synaptic strengthening
Hippocampus
Also studied in other brain areas
What does one high frequency electrical stimulation lead to?
LTP lasting hours
What do multiple high frequency electrical stimulation lead to?
Lasts days and months
Why is long term potentiation temporal?
Summation of inputs reaches a stimulus threshold that leads to the induction of LTP. e.g. Repetitive stimulation (HFS)
Why is long term potentiation associative?
simultaneous stimulation of a strong and weak pathway will induce LTP at both pathways. (Spatial summation)
Coincidence detection
“Cells that fire together wire together”
Why is long term potentiation specific?
LTP at one synapse is not propagated to adjacent synapses (input specific)
What happens at the synapse?
Glutamate released onto inactive cell
AMPA receptor activated to cause early phase EPSP
NMDA receptor blocked by Mg2+ and depolarization from AMPA activation is not sufficient to expel Mg2+
High frequency stimulation leads to high amounts of glutamate released onto active cell (membrane depolarized). AMPA receptor activated and Mg2+ block on receptor relieved. Na+ through AMPA and NMDA channels. Ca2+ through NMDA receptor,
Ca2+ entry through NMDA receptor activate PKC and CaMkII
What do PKC and CaMKII do?
Phosphorylate existing AMPA receptors, increasing their effectiveness
Stimulate the insertion of new AMPA receptors in the membrane. LTP
What does CaMKII do?
Sustained activity after repolarization
Autocatalytic activity - becomes phosphorylated
Constantly active - no longer requires Ca2+
Maintains phosphorylation, insertion of AMPA receptors after depolarisation has receded
Molecular switch which maintains increased excitability of neuron for minutes to hours
How is Nitric oxide used in long term potentiation?
Postsynaptic neuron feeds back to presynaptic neuron by retrograde neurotransmitter NO
Ca2+ through NMDA channel activates Nitric oxide synthase
NO diffuses from site of production and activates guanylyl cyclase in presynaptic terminal
Guanylyl cyclase produces cGMP
Signal transduction cascade leads to increased
glutamate release from the synaptic button
List the stages of memory formation
Acquisition (training)
Consolidation
Recall (testing)
What is protein synthesis required for?
Long lasting LTP
Consolidation of long term memories
What is CREB?
cAMP Response Element Binding protein activated by phosphorylation by a number of kinases (PKA, CaMKII etc)
What is early phase LTP?
lasts a minute to an hour and can be explained by the actions of Ca2+ through the NMDA receptor and subsequent enhancement of AMPA receptor efficiency, presynaptic events etc.
What is late phase LTP?
lasts hours, days or months -requires new protein synthesis and can involve morphological changes and the establishment of new synapses
What do Ca2+ activated signal transduction cascades do?
activate new protein synthesis from
dendritically localized mRNAs
filter back to the cell body to
stimulate new gene transcription (CREB -mediated), protein synthesis
and recruitment of new proteins to the synapse
What is long term depression?
Process of forgetting
Low frequency stimulation causes a decrease in EPSP amplitude
NMDA dependant process
AMPA receptors are dephosphorylated and removed from the membrane
Prolonged low level rises in Ca 2+ activates phosphatases rather than kinases
LTP and LTD reflect bidirectional regulation of …
- phosphorylation
2. number of postsynaptic AMPA receptors
How is the LTP and LTD hypothesis proved?
AP5 infused into hippocampus of rats shows no memory of morris water maze
Describe the effect of alcohol on learning and memory
NMDA receptor antagonist (as well as other sites)
Blackouts and amnesia caused by drinking - directly blocking normal LTP processes?
Alcohol disrupts hippocampal theta rhythms and disrupts short term memory.
Chronic alcoholism and associated nutritional deficiency can result to Korsakoff syndrome or psychosis: loss of recent memory, and tendency to fabricate accounts of recent events (confabulation).
Describe the effect of barbiturates on learning and memory
Indirect agonist of GABAA receptors:
- binding increases the receptor affinity for GABA
- increase frequency of channel opening
- anxiolytic and hypnotic drugs
Side effect to anxiolytic and sedative properties:
- anterograde amnesia
Describe the effect of cholinergics and anticholinergics on learning and 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 and impairs spatial learning
What drug is used in alzheimer’s?
Acetylcholinesterase inhibitors
(e.g. physostigmine)
Boost cholinergic function
Improves memory impairments
What is the effect of acetylcholinesterase inhibitors in a healthy brain?
Controversial as to whether they improve memory
May increase attention
Most cognitive enhancing effects of both acetylcholinesterases and other cholinergic drugs, e.g. nicotine, seen in impaired subjects, i.e. Alzheimer’s patients, or in restoring performance of animals with lesions.
What other learning processes use LTP?
Activity dependent synaptogenesis (development)
Motor learning - e.g. riding a bike - cerebellar
