LTP Mechanisms Flashcards
What is a Hebbian synapse?
A synapse that is strengthened by coordinated activity of the pre and postsynaptic neuron
Which part of the brain is involved in learning and memory?
Hippocampus
What is the circuit structure in the hippocampus? (4)
- Entorhinal cortex to the dentate gyrus (perforant pathway)
- Dentate gyrus to CA3 (mossy fibres)
- CA3 to CA1 (Schaffer collaterals)
- Output via the fornix and subiculum
What is an EPSP?
Excitatory Post Synaptic Potential
What happens when you apply a high frequency stimulus to a neuron?
The EPSP amplitude gets bigger and more prolonged
What is LTP? (2)
- Long Term Potentiation
- When synapses become stronger with frequent activation
How is LTP input specific?
The increased amplitude EPSP only occurs at the synapse that has been frequently stimulated, not all synapses that contact the neuron
Where does LTP usually occur?
CA3 to CA1 synapses in the hippocampus
What is LTP cooperativity? (3)
- Two pathways converging on the same target are both strengthened if they fire together
- Doesn’t require high frequency stimulation
- May explain associative learning
What are the 3 types of glutamate receptors?
- NMDA receptor
- AMPA (non-NMDA) receptor
- mGlut receptor
What type of synapse is between CA3 and CA1 neurons?
Glutamatergic
What type of receptor is an NMDA receptor?
Ion channel
What type of receptor is an AMPA receptor?
Ion channel
What type of receptor is an mGlut receptor?
Metabotropic
How do NMDA receptors work? (3)
- Mg2+ block is removed by depolarisation
- Glutamate binds = channel opens
- Mostly Ca2+ and some Na+ enter the neuron through the channel
How do AMPA receptors work? (2)
- Glutamate binds = channel opens
- Permeable to Na+ and K+ so causes depolarisation of the neuron
Which glutamate receptor is the main one for transmission of information?
AMPA receptor
How does LTP occur? (4)
- High frequency stimulation causes glutamate release which activates AMPA receptors = depolarisation
- Depolarisation + glutamate activates NMDA receptors by removing the Mg2+ block
- Ca2+ influx through NMDA receptors activates kinases (caMKII)
- Phosphorylation of proteins causes increase in EPSP = LTP
What are the 2 phases of LTP?
Early (induction) and late (expression)
What changes are caused by LTP? (3)
- Increase in vesicle release rate
- Increase in number of synapses
- Increase in number of postsynaptic receptors
Are the biggest changes in LTP pre or postsynaptic?
Postsynaptic
How is caMKII activated?
Binding of Ca2+/calmodulin complex
What happens during early phase LTP? (4)
- Ca2+ influx via NMDAR activates caMKII which phosphorylates downstream proteins
- Phosphorylation increases the amplitude of AMPA currents in response to glutamate
- Phosphorylation of AMPA receptors may increase current through individual channels
- May involve AMPAfication
How does CaMKII work? (3)
- CaMKII contains regulatory and catalytic subunit
- Binding of Ca2+/calmodulin causes a conformational change = active
- CaMKII autophosphorylation which stabilises CaMKII in the active conformation so can work in the absence of Ca2+/calmodulin
What is AMPAfication?
An increase in the number of AMPA receptors in the postsynaptic membrane
What happens during late phase LTP? (5)
- cAMP activates pKA which enters the nucleus
- CREB-2 is bound to CRE sequence in DNA
- CREB-2 substituted by CREB-1
- CREB-1 is phosphorylated by pKA and causes transcription
- Newly made proteins travel to the synapse
Why does late phase LTP take longer?
Involves changes in gene expression and protein synthesis
What are nootropics?
Drugs that enhance memory
What is the effect of inhibiting LTP on memory formation?
Inhibits memory formation - LTP required for memory formation
What experiment can be used to examine the link between LTP and memory? (2)
- Morris water maze
- Mouse swims around a pool until it finds a submerged platform, repeat the experiment, the mouse learns where the platform is hidden and finds it quicker
