Synaptic Plasticity Flashcards
Synaptic Plasticity is
the ability to reorganise by creating new neural pathways to adapt
Mechanisms of synaptic plasticity could include:
- altering the amount of
neurotransmitter released - changing the no. receptors post-
synaptically - changing signaling molecules inside
neuron - changing gene transcription
Synaptic efficacy/strength changes with —–, many of these changes are ——- dependent
- time
- activity
Learning:
involves adaptive changes in synaptic connectivity which will in turn alter behaviour
Hebb’s Rule:
synapses can change conformation depending on how active or inactive it is
Hebb’s Cell Assembly:
internal representation of an object consists of the cortical cells that are activated by it - cell assembly - cells were reciprocally interconnected
Hebb’s cell assembly hypothesis:
- activation of the cell assembly
persisted long enough leading to
consolidation/growth process - reciprocal connection would be more
effective; fire together and wire
together - subsequently, if only a fraction of
assembly cells were activated by a
later stimulus, the strengthened
connections could cause the whole
assembly to activate
Rules of Synaptic Modification:
- fire together wire together
- fire out of sync lose their link
- individual stimulation may be
insufficient to fire an action potential - summation of two signals is
acceptable
Connectome:
- system of neural pathways in a brain
or nervous system considered
collectively
Long-Term Potentiation:
- mechanism underlying synaptic
strengthening - describes a phenomenon whereby
high frequency stimulation of a
neurone leads to increased EPSP to a
subsequent single stimulus pulse - long-term changes in expression of
genes and turnover of peptides
undelry this phenomenon = a form
of plasticity
An example of long term potentiation is
high frequency electrical stimulation of the perforant pathway
Excitatory postsynaptic potential can last hours
Cellular Physiology of LTP:
- Glutamate release onto membrane
at resting potential - AMPA receptor activated to create
EPSP - NMDA receptor blocked by Mg2+
- depolarisation from AMPA activation
not sufficient to expel Mg2+ - Glutamate release continued onto
active (depolarised) cell - AMPA receptor activated
- Mg2+ block on NMDA removed
- Na+ enters through AMPA and
NMDA channels - Ca2+ through NMDA receptors
- leads to the activation of protein
kinase C, CaMKII (Calcium
calmodulin-dependent protein
kinase II)
1)phosphorylates existing AMP
receptors increasing their
effectiveness
2) stimulates the insertion of new
AMPA receptors into the membrane
CaMKII Molecular Switch:
- has autocatalytic activity so becomes
phosphorylated - constitutively active; no longer
requires Ca2+ - maintains phosphorylation, insertion
of AMPA after depolarising stimulus
has receded - molecular switch which maintains
increased excitability of neuron for
minutes to hours
Early Phase Long-term potentiation:
- a minute to an hour
- explained by the actions of Ca2+ and
the subsequent enhancement of
AMPA receptors, presynaptic events
etc
Late Phase Long-Term Potentiation:
- hours, days, months
- requires new protein synthesis
- can involve morphological changes
and new synapses - Ca2+ activated signal transduction
Before and after of what?
Long-term potentiation and Pre-synaptic Events:
- post-synaptic neuron can feed back
to the presynaptic by retrograde
neurotransmitter - Nitric Oxide - Ca2+ entry activates enzyme NO
synthase leading to the production
of Nitric Oxide - NO diffuses and activates guaynyl
cyclase in the presynaptic terminal - Guanylyl cyclase produces the
second messenger cGMP - signal transduction cascade leads to
increased glutamate release from
the synaptic button
LTP and Pre-synaptic Neuron:
Synaptic Plasticity and Excitotoxicity:
- glutamate, AMPA, NMDA receptors
- ***calcium overload is the essential
factor in excitotoxicity - importance of mechanisms that
counteract the rise in cytosolic free
Ca2+ efflux pump and indirectly the
sodium pump - Mitochondria and ER keep Ca2+
under control - Disruption of mitochondrial function
disrupts ER, no balance, increase of
Ca2+ - mitochondria might be an essential
organelle in the control of Ca2+
mediated toxicity
needed or unneeded?
Long-term Depression:
- low frequency stimulation causes
long term depression and rather
than getting an increase in EPSP
amplitude on further stimulation you
get a decrease - NMDA dependent
- AMPA receptors are de-
phosphorylated and removed from
the membrane - prolonged low level rises in Ca2+
activate phosphatases which remove
the phosphates rather than kinases
Long Term Depression
NMDA receptor activity in the medulla is essential for both LTP and spatial learning.
True or False?
False
NMDA receptor activity in the hippocampus is essential both LTP and spatial learning
Experimental evidence for the role of LTP in memory formation and learning:
- AP5 is NMDA receptor
- blocks hippocampal LTP
- rat is unable to learn how to get out
of the maze - London taxi drivers have an
increased volume of grey matter in
hippocampus due to short-term
memory and spatial navigation - learning a second language
increases density of grey matter in
the left inferior parietal cortex - playing video games for 30mins a
day increases brain matter in the
cortex, hippocampus and cerebellum - new connections in sites controlling
spatial navigation, planning and
decision-making
Alcohol and Learning/Memory:
- NMDA antagonist
- blackouts and amnesia
- blocking normal LTP processes
- disrupts short term memory
- chronic alcoholism and associated
nutritional deficiency can result in
Korsakoff syndrome or psychosis:
loss of recent memory, tendency to
fabricate accounts of recent events
Benzodiazepine and Learning/Memory:
- modulators of GABA a receptor
- can lead to anterograde amnesia
Cholinergics/Anticholinergics and Learning/Memory:
- role of ach in learning and memory
- muscarinic antagonist seems to
impair spatial learning - use of acetylcholinesterase inhibitors
for alzheimers
Reduced sensitivity of mu opiod receptor with long termmorphine can result in
abnormal synaptic plasticity
Increased numbers of specific nicotinic receptor subunits in the brains of smokers can result in
abnormal synaptic plasticity
Addiction can perceives in part as a
pathological form of learning and memory
