Question

Neuroscience: Synaptic Physiology:

Describe the cellular and molecular mechanisms underlying Long Term Potentiation and Long Term Depression.

Focus on trafficking of new AMPA receptors and phosphorylation of existing AMPA receptors.

Also describe the stimulation pattern and the necessary cellular events that lead to the observed changes.

Answer 1

Long term potentiation (LTP) and Long term depression (LTD) are excitatory synapses and are forms of synaptic plasticity. Phosphorylation of GluR1 subunit of AMPA receptor is critical step for LTP and LTD induction or expression.

Mechanism of LTP :

1. AMPA receptors get excited and leads to influx of Na+ and thus post-synaptic cell become depolarised.
2. Post synaptic cell now release Mg+ ions and block NMDA receptors so as to allow Calcium-glutamate molecule to enter cell.
3. CaMKII and PKC are two protein kinases which get activated now and proceed 2 steps :

• Phosphorylation of existing AMPA receptors
• Increase in post-synaptic new AMPA receptors  

Mechanism of LTD :

1. LTD is opposite process of LTP which decreases efficacy of synapse.
2. LTD progresses as there is increase in post-synaptic Ca+ and low frequency stimulus.
3. In cerebellum, decrease in efficacy of synapse occurs due to phosphorylation of AMPA receptors whereas in hippocampus, decrease in efficacy of synapse occurs due to very low Ca+ level and activated phosphatases which carry out dephosphorylation of AMPA receptors.

Answer 2

Ans 1.

Long-term potentiation (LTP) and long-term depression (LTD) in neurosciences, of synaptic transmission are widely recognized as representing cellular mechanisms used by a variety of neuronal networks to store certain types of information. The molecular and cellular events underlying these forms of activity-dependent synaptic plasticity are also being elucidated. Like learning and memory processes, LTP and LTD undergo age-related alterations. These interaction are not only strengthen the links between LTP/LTD and learning and memory but also provide a cell biology interpretation of age-related modifications at the cellular and systems level.

Ans.2

AMPA receptors are provide the initial depolarization that ultimately results in NMDA receptor activation.

Trafficking of AMPA receptors is a fundamental mechanism underlying synaptic plasticity and has been shown to be an important process in higher brain functions such as learning and memory. The AMPA receptor binds at least two “structural” proteins—PICK-1, which binds PKC, and GRIP. GRIP is a multi-domain scaffolding protein that likely functions in AMPA receptortrafficking. GRIP also binds to GRASP1, a GEF for ras —the functional role of GRASP1 at the synapse is unclear at present.

An increase in AMPA receptor function could be due to up-regulation of functional synaptic receptors or by phosphorylation of existing synaptic receptors. Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory.

Ans 3

the stimulation pattern and the necessary cellular events that lead to the observed changes like molecular and cellular events underlying these forms of activity-dependent synaptic plasticity are also being elucidated. Like learning and memory processes, LTP and LTD undergo age-related alterations.

there are various stimulation patterns are presents. Common stimulation patterns studied are constant frequency trains (CFTs), variable frequency trains (VFTs), and doublet frequency trains (DFTs).

CFTs are stimulation trains in which the frequency remains constant throughout the entire train. In contrast, VFTs are usually trains that begin with an initial doublet, (two closely spaced pulses, typically 5-10 µs apart) followed by pulses at a chosen frequency.