Synaptic plasticity Flashcards
Implicit memory
Type of long-term memory
- Also called Non-declarative memory/ procedural memory
Develops in an automatic manner—> involuntary
Includes:
Priming- Neocortex
Learning of motor skills- Striatum
Habit memory- Reflex pathways
Conditioning- amygdala and cerebellum
Explicit memory
Type of long term memory
- Also called declarative memory
Requires conscious retrieval
Two categories
- Semantic: Knowledge of facts and concepts
- Episodic: Knowledge of personal experience and autobiographical memory
Anatomical region
- Medial temporal lobe
- Midbrain
Learning
Response of the brain to environmental changes, which leads to a change in behaviour
- As a result of adaptive changes in synaptic connectivity
Rules of synaptic modification [Hebb’s rule]
- Neurons that fire together are wired together.
2. Neurones that fire out of sync, lose their link.
Cell assembly
Cells that are associated as a result of simultaneous firing
- Mechanism for learning.
- Neurones have reciprocal connections and are activated by a stimulus.
- Activity of the neurones still continue after the stimulus has been removed.
- Continuous, simultaneous firing of neurones strengthen reciprocal connections.
- The strengthened connections are still present in an engram, even when not activated.
- Even a partial activation of the cell assembly can active the entire circuit in learning.
Long term potentiation (LTP)
A long lasting increase in the amplitude of Excitatory post-synaptic potential
- After stimulation of high frequency electrical stimulation
The length of LTP can vary in time
- Minutes/ hours, as result of exposure to one high frequency stimulus [HFS]
- Days/ months—> multiple HFS
LTP in hippocampus
Entorhinal cortex is connected to the hippocampus through perforant pathways.
- Connects to cells within the dentate gyrus
High frequency stimulation of the axons in the perforant pathway led to long lasting increase in EPSPs on the dentate gyrus neurones.
Categories of LTP
Temporal [repetitive summation]
- Inputs arrive at the same time —> reaches threshold for LTP.
Associative [spatial summation]
- Simultaneous stimulation from strong and weak stimuli induce LTP
Specific
- LTP at one synapse is not extended to the next synapse
- Makes the input specific
Molecular mechanism of early-phase LTP
Lasts minute- hour
- Continuous stimulation by glutamate [HFS] on NDMA and AMPA receptors.
- Causes depolarisation of cell membrane - Na+ flux into NDMA and AMPA channels.
- Ca2+ flux into NDMA channels.
- Ca2+ activates PKC and CaMKII - PKC and CaMKII phosphorylates AMPA receptors= increases their effectiveness
- PCK and CaMKII also stimulates insertion of new AMPA receptors into the plasma membrane/
Late phase LTP
Lasts Hours-months
Occurs as a result in activation of new protein synthesis from dendritically localised mRNA.
CREB-2 [binding protein] is activated through phosphorylation from kinases [PKC, CaMKII]–> CREB-1
- Kinases created as a result of increased Ca2+ that comes with HFS
Activated CREB stimulates transcription of proteins into the plasma membrane/
Protein synthesis inhibitors in late-stage LTP
Prevent the consolidation of long-term memory and LTP
Example
- Inhibitors injected post-training of memory formation = inability to consolidate memory
CaMKII molecular switch
Mechanism for LTP in post-synaptic neurone.
- Influx of Ca2+ through NMDA receptors, activate CaMKII.
- CaMKII phosphorylates itself [autocatalytic] and AMPA receptors.
- Phosphorylation is sustained without Ca2+ stimulus.
This sustained activation fo CaMKII increases the excitability of the neurone
Pre-synaptic events in LTP
Ca2+ influx into post-synaptic cell, activates NO synthase.
NO synthase—-> NO
- Retrograde signalling to presynaptic button.
NO activated guanylyl cyclase—–> activates cGMP
Increased cGMP= increased glutamate release from pre-synaptic button.
Morris Water maze
Experiment that demonstrates the importance of NMDA receptors in learning.
AP5 [NMDA r. antagonist] was injected in rats.
Rats were placed in water maze that required them to find a platform
- Rats with AP5 never learned to find the platform despite finding it before.
Alcohol on memory
NMDA r. antagonist.
- Causes blackouts and amnesia.
Alcohol also disrupts
- Hippocampal theta rhythms [REM sleep}
- Short term memory
Chronic alcoholism
- Nutritional deficiency
- Korsakoff syndrome—> loss of recent memory, confabulation
