Question

Long-term Potentiation (LTP) and Long-term Depression (LTD). Please discuss these two forms of synaptic plasticity that can be studied in research and represent molecular and cellular events underlying activity-dependent synaptic plasticity. What are LTP and LTD? What chain or cascade of events takes place that lead to LTP AND LTD? Specifically now address Early vs. Late LTP and effects of cAMP and PKA...

Answer 1

LTP
it is the process by which the synaptic connection between the neurons become stronger with frequent activation.LTP is thought to be a way in which the brain changes in response to experience, and thus maybe e mechanism underlying learning and memory.
There are a number of ways in which LTP can occur. The best-known mechanism involves a glutamate receptor known as NMDA receptor. in NMDA receptor dependent LTP, glutamate release first activates a subtype of glutamate receptor known as the AMPA receptor.NMDA receptors are found nearby these AMPA receptors, but are not activated by low levels of glutamate release because the Ion channels of an NMDA receptor is blocked by a magnesium ion. If frequent action potentials cause greater stimulation of AMPA receptors, however, this will cause the postsynaptic neuron to depolarize which eventually causes the voltage-dependent magnesium blockage of the NMDA receptor to be removed, allowing calcium ions to flow in through NMDA receptor. This influx of calcium initiates cellular mechanisms that cause more AMPA receptors to be inserted into the neurones membrane. The new AMPA receptors are also more responsive to glutamate, and allow more positively charged ions to enter the cell when activated.Now the postsynaptic cell is more sensitive to glutamate because it has more receptors to respond to it. Additionally there are thought to be signals that travel back across the synapse to stimulate greater levels of glutamate release.All of this makes the synapse stronger and more likely to be activated in the future.this process is also associated with changes in gene transcription in the neurone,which can lead to the production of new receptors or modifications to the structure of the cell.these changes seem to be important for making the increased responsiveness of LTP long-lasting.

LTD
LTD IS A PROCESS BY WHICH SYNAPTIC CONNECTIONS BETWEEN NEURONES BECOME WEAKER.
It is the opposite process to long term potentiation. Although the functions of LTD are not completely understood it is thought to be importantto memory formation perhaps by resetting previous synaptic changes to allow for new memories to be formed via long term potentiation. There are several different mechanism by which ltd may occur.But the best understood of them involves the same glutamate receptors involved in long term potentiation: NMDA & AMPA receptors.NMDA receptors are typically blocked by a magnesium Ion which is only removed if the postsynaptic neurone becomes sufficiently depolarized as can occur through activation of the AMPA receptor;when the block is removed calcium is able to flow into the neurone, causing further while long-term potentiation typically occurs after brief but high intensity stimulation.while long term potentiation typically occurs after brief but high intensity stimulation of a postsynaptic neurone LTD can be caused by prolonged long intensity stimulation or stimulation that occurs after the firing of an action potential. With the type of modest stimulation that result in LTD, there is not enough depolarization to cause widespread removal of the magnesium blockage of the NMDA receptor. However there is enough to cause some NMDA receptors to allow calcium into the cell.this is low level of calcium is insufficient to activate the enzymes that facilitate long-term potentiation, but it is thought to activate a cellular cascade that causes the removal of AMPA receptors.This reduces the number of glutamate receptors on the postsynaptic neurone and weakens the synapse.LTD may also result in other changes that decrease the strength of the synopses, like a decrease in the amount of glutamate released from the presynaptic neuron, and it also caninvolve other receptors like metabotropic glutamate receptors or other neurotransmitter receptors altogether.

• Early LTP :

1. Neuronal changes are temporary & wear off after a few hours, depend on short term kinase activity.
2. First phase of LTP
3. Increased synaptic strength
4. LTP produced by the repetitive stimulation of the presynaptic terminals.
5. Play a major role in memory function in hippocampus amygdala and other cortical brain structures.

• Late LTP :

1. Neronal changes are much more stable and long-lasting, at least remains for 8 hours; depends on denovo gene transcription.
2. Second phase of LTP
3. Persistent strengthening of synapse.
4. Induced by change in gene expression and protein synthesise brought about by persistent activation of protein kinase activity.

Effect of cAMP & PKA on LTP:

Long-term potentiation (LTP) has two phases, and there is general agreement that the late phase of LTP requires the activation of adenylyl cyclase (AC) and cAMP-dependentprotein kinase (PKA). The early LTP is not affected by interfering with the cAMP pathway.