Exam 3: SYNAPTIC PLASTICITY Flashcards
what is plasticity?
A. Synapses are dynamic—in response to neural activity and other factors, synapses will change (strengthen, weaken etc.). These changes are termed plasticity
B. Plasticity can be short term or long term; plasticity underlies learning and memory, along with any higher order cognitive process
what is responsible for causing potentiation?
Potentiation is a rapid increase in synaptic strength that occurs when two or more action potentials invade the presynaptic terminal within a few milliseconds. This type is thought to be mediated by presynaptic calcium increase
what is responsible for causing depression?
Synaptic depression is when a decrease in neurotransmission occurs followed repeated activity. The theory is that depletion of vesicular pools of neurotransmitter occurs with activity, which decreases available neurotransmitters for release
1) Decreasing the external calcium causes decreased neurotransmitter release
2) Total amount of depression is linked to amount of neurotransmitter that was released
what is long-term potentiation?
Long-term synaptic plasticity can increase synaptic strength, known as long-term potentiation (LTP)
What does LTP require presynaptically and postsynaptically (in broad terms)?
Brief, high frequency stimulation leads to LTP
1) LTP requires that both the presynaptic and postsynaptic neuron are active together temporally, meaning both neurons are undergoing depolarization
- This type of linked activity would strengthen a synapse between the two neurons that fired and facilitate learning/memory
What is needed for the initial acquisition of LTP?
With both LTP and LTD, timing of presynaptic and postsynaptic firing is very important—neurons have to fire within 100ms together to be coupled for LTP/LTD. This is termed spike timing dependent plasticity
What additional factors are needed for the maintenance of long-lasting LTP?
CHANGES TO GENE EXPRESSION
1. Blocking protein synthesis several hours after LTP initiation blocks LTP. Blocking protein synthesis earlier than that has no effect. Thus, there is a late phase of LTP that requires changes to gene expression.
- Protein kinase A (PKA) activates transcription factors like CREB, which go into the nucleus and alter expression of genes which in turn alters protein expression
- The proteins that have been shown to be upregulated include AMPA receptors
LTP :What receptors are involved? Why do you need both NMDA and AMPA?
The NMDA receptor has a Mg 2+ block, which requires depolarization to relieve. Thus, only high frequency stimulation activates this receptor. With low-frequency stimulation, AMPA receptors are activated only.
With brief high frequency stimulation, the magnesium block is relieved and calcium can enter the neuron. The calcium is crucial for LTP, so the NMDA receptor is the coincidence detector
What is long-term depression (LTD)? How does it occur?
Long-term synaptic plasticity can decrease synaptic strength, known as long-term depression (LTD)
What does LTD require presynaptically and postsynaptically (in broad terms)?
prolonged, low frequency stimulation leads to LTD.
Long, low frequency stimulation depresses EPSPs and this weakens synaptic connections that were strengthened by LTP
Compare cellular mechanisms involved in LTP versus LTD
1) Glutamate binding the NMDA receptor is also involved in LTD. Calcium entry that results from long, low frequenct stimulation causes LTD. Recall that with LTP, brief, high frequency stimulation flood the neuron with calcium
2) The calcium entry binds to phosphatases that remove phosphate groups from target proteins. Recall that in LTP, kinases add phosphate groups
3) Loss of AMPA receptors is seen in LTD, whereas LTP led to extra AMPA receptor on the membrane
How is LTP affected in Alzheimer’s disease? By what mechanism?
- Many disease/disorders of the nervous system will produce long-term dysfunction due to GPCR over activation and subsequent CREB involvement
1. Alzheimer’s disease, characterized by the presence of Aβ plaques and tangles that are correlated with neurodegeneration, involves CREB
2. It is thought that the Aβ plaques can decrease cAMP/PKA levels and therefore decrease CREB levels
3. This has the greatest effect on learning/memory because long-term potentiation (LTP) heavily relies on PKA, and prolonged dysfunction in this pathway can lead to neurodegeneration
