L19 Synaptic plasticity Flashcards
what are the different types of memory
Explicit- includes declarative memory:
1)facts
and
2) events
Implicit- non-declarative money:
1) procedural memory: skills and habits
2) Classical conditioning: Skeletal musculature
3) Classical conditioning- emotional responses
where are the areas that the different types of memory found in the brain
Explicit: Medial temporal lobs; diencephalon
Implicit: Procedural
memory :
striatum
classical-skeletal musculature: cerebellum
Emotional responses: Amygdala
describe; how do we learn
- Learning: the response of the brain to environmental events and involves adaptive changes in synaptic connectivity which will in turn alter behaviour.
describe the Donald Hebb cell assembly theory
1) Reciprocal connections exist between neurons; forming a cell assembly
2) An external stimulus is applied
3) Activation of the cell assembly by a stimulus
4) Reverberating activity continues activation after the stimulus is removed
5) Hebbian modification strengthens the reciprocal connection between neurons that are active at the same time
6) The strengthened connections of the cell assembly contain the engram for the stimulus
7) After learning, partial activation of the assembly leads to activation of the entire representation of the stimulus
8) Circle/cell assembly is formed
summarise Hebb’s rule
-When an axon of cellAis near enough to excite a cellBand repeatedly or 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 firingB, is increased
=
Strengthening and weakening synaptic connections in the brain provide a means by which learning occurs and memories can be formed.
describe the rules of synaptic modification
1) Neurons that fire together wire together
2) Neurons that fire out of sync lose their link.
read over slide 13 for an example of rules of synaptic modification
how was it?
why is the hippocampus regularly tested and what is it used to study
shape and anatomy means pathways can be easily distinguished and recorded from electrophysiologically
used to study Long term potentiation (LTP)
what does LTP underlie
- mechanism underlying synaptic strengthening
describe Temporal LTP
- Temporal: Summation of inputs reaches a stimulus threshold that leads to the induction of LTP. e.g. Repetitive stimulation (HFS)
describe Associative LTP
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”
describe specific LTP
Specific: LTP at one synapse is not propagated to adjacent synapses (input specific).
what occurs at the synapse during LTP
Glutamate release onto inactive cell
(membrane at resting potential)
AMPA receptor activated to create EPSP
NMDA receptor blocked by Mg2+ ion
Depolarization from AMPA activation
not sufficient to expel Mg2+
Glutamate release onto an active
Cell (membrane depolarized)
AMPA receptor activated
Mg2+ block on NMDA receptor relieved
Na+ through AMPA and NMDA channels
Ca2+ through NMDA channel
what happens when Ca2+ enters through the NMDA channel
Ca2+ entry through the NMDA receptor leads to activation of:
Protein kinase C
Calcium calmodulin-dependent protein kinase II (CaMKII)
1) phosphorylates existing AMPA receptors, increasing their effectiveness
2) stimulates the insertion of new AMPA receptors into the membrane
describe the before and after depolarisation correlation between the number of AMPA receptors and an EPSPs
1)Before:
Few AMPA receptors
Small EPSPs
2)After:
More AMPA receptors working more effectively
Larger EPSPs
LTP
describe the activity of the CaMKII - molecular switch - which has sustained activity after repolarization
1)Ca2+ entry through the NMDA receptor leads to activation of
Calcium calmodulin-dependent protein kinase II (CaMKII)
2) CaMKII has autocatalytic activity - becomes phosphorylated
3) When phosphorylated is constitutively active - no longer requires Ca2+
4) Maintains phosphorylation, insertion of AMPA receptors etc. after the depolarizing stimulus has receded
5) Molecular switch which maintains increased excitability of neuron for minutes to hours
what are the presynaptic events in a LTP
1)Postsynaptic neuron can feed back to presynaptic neuron by retrograde neurotransmitter - Nitric Oxide (NO)
2)Ca2+ through the NMDA channel
activates Nitric oxide synthase
3)NO diffuses from site of production and
activates guanylyl cyclase in the presynaptic
terminal
4)Guanylyl cyclase produces the
second messenger cGMP
5)Signal transduction cascade leads to increased
glutamate release from the synaptic button
describe what occurs in a late phase LTP
1) Protein synthesis required for long-lasting LTP (days, months)
2) Protein synthesis inhibitors prevent the consolidation of long term memories and LTP
3) Stages of memory formation
4)Acquisition (training)
Consolidation
Recall (testing)
5)Protein synthesis inhibitor
injected just post-acquisition
(training) inhibits recall
- necessary for consolidation
6)CREB - cAMP Response Element Binding protein activated by phosphorylation by a number of kinases (PKA, CaMKII etc)
describe the difference between early and late phase LTPs( starting with early) Part 1/2
1) lasts a minute to an hour
2) and can be explained by the actions of Ca2+ through the NMDA receptor and subsequent enhancement of AMPA receptor efficiency
3) presynaptic events etc.
describe the difference between early and late phase LTPs( ending with late) Part 2/2
1) lasts hours, days or months
2) requires new protein synthesis
and can involve morphological
changes and the establishment
of new synapses
3) Ca2+ activated signal transduction
cascades:
A- activate new protein synthesis from
dendritically localized mRNAs
B-filter back to the cell body to
stimulate new gene transcription (CREB -mediated), protein synthesis
and recruitment of new proteins to the synapse
describe what LTD is
Long Term Depression (LTD)=
-
Low frequency stimulation (LFS: 100x 1 Hz) actually causes the opposite and rather than getting an increase in EPSP amplitude on further stimulation you get a decrease
Same players involved:
-NMDA dependant process
-AMPA receptors are de-phosphorylated and
removed from the membrane
-prolonged low level rises in Ca2+ activate
phosphatases rather than kinases
what do LTP and LTD reflect bidirectional regulation of
- phosphorylation and
2. number of postsynaptic AMPA receptors
what is the proof that changes in synaptic activity really lead to learning
in Rats:
1) NMDA receptor activity in the hippocampus essential for both LTP and spatial learning
2) AP5
- NMDA receptor antagonist
-blocks hippocampal LTP
blocks learning in the Morris Water Maze
3) conclusion: normal rat without AP5 learned uickly to find the way to escape the water maze
but
the rats with AP5 infused struggled to escape after multiple trials
describe the studies done on humans in regards to LTP
Human inferotemporal cortex
removed during surgery
maintained in vitro
HFS - produced LTP
LFS - produced LTD
what are the effects of acute and chronic alcohol on memory and learning
Alcohol -
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).
what are the effects of benzodiazepines on learning and memory
- Benzodiazepines
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 effects of cholinergics/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
describe the effects of cholinergics/anticholinergics on learning and memory in Alzheimers
Alzheimer’s disease
Acetylcholinesterase inhibitors
e.g. physostigmine
Boost cholinergic function
Improves memory impairments
describe the effects of cholinergics/anticholinergics on learning and memory 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.
name some other processes which use LTP
Activity dependent synaptogenesis (development)
Motor learning - e.g. riding a bike - cerebellar
