Thank you sooo much for your help, I really appreciate :) You just discovered, f

Question

Thank you sooo much for your help, I really appreciate :) You just discovered, for the first time, that LTP causes learning In your Nobel Prize acceptance speech, after thanking me of course, you decide to describe thes molecular changes involved in LTPI Here, list/describe/depict all steps covered in class. Your answer should include: how AMPA and different, why this matters, how a particular protein kinase is activated, iwo important ways this protein kinase contributes to LTP, how a particular ranscription factor is activated, how the transeription factor contributes to LTP how retrograde messengers contribute receptors are

Explanation / Answer

Long term Potentiation (LTD) occurs when the presynaptic neuron spike that precedes a postsynaptic neuron spike within a narrow time window. N-methyl-d-aspartate (NMDA) receptor and AMPA receptors are involved in LTP, which is involved in learning and memory. Best characterized LTP occurs between CA3 and CA1 pyramidal neurons of the hippocampus.

When the presynaptic neuron is triggered, the neurotransmitter is released from the synaptic vesicle, which diffuses rapidly across the synaptic cleft of the post synaptic membrane. The neurotransmitter binds to ionotrophic receptors, which are direct ligand-gated ion channels. Excitatory neurotransmitter is glutamate while inhibitory neurotransmitter is GABA.

NMDA and AMPA-type glutamate receptors (NMDARs, AMPARs) are ionotropic receptors. Both these receptors are permeable to Na+ and K+. AMPAR drives rapid large synaptic signaling. They can be homo-or heterodimers resulting in four subunits. AMPARs carry inward currents at negative potentials. The outward currents are carried at positive potentials. They follow a linear current-voltage relationship. The reversal potential is 0mv. AMPARs only allow Na+ and K+ to flow though, and have no Mg block.

NMDAR has slow kinetics than AMPARs. At negative membrane potentials (resting membrane potential), magnesium ions enter the pore of the NMDAR. These Mg ions block the passage of all other ions. When the membrane depolarizes, magnesium is expelled from the pore. As a result, allowing sodium, potassium, and calcium ions can pass through the pore. NMDARs allow maximal permeability with large outward currents at positive potential. A 30 mv of depolarization is required for NMDA channel to open.

AMPAR are first activated by binding of glutamate. This results in movement of sodium inside the cell, and depolarization of the membrane. The EPSPs generated by AMPAR activation accumulate over time to cause the depolarization. This depolarization will remove the Mg block on the NMDA receptor by the removal of Mg ions at the pores. When the depolarization reaches 30mV, the NMDAR is activated, resulting in movement of calcium inside the cell. Entry of calcium into the cell activates calcium/calmodulin-dependent protein kinase II (CaMK II) kinases. The Ca2+/CaM complex binds to specific contiguous sequence. Hence, the Ca2+ is displaced causing autophosphorylation of CaMK II at Thr286, and movement to the synapse. Activated CaMK II bind to proteins, such as ?-actinin, PSD-95, synaptic adhesion molecule, and densin-180. It can activate microtubule-associated protein 2 (MAP2) and neurofilament L, which are required for synaptic plasticity

Other kinase activated are protein kinases A and C. These kinases activate mitogen-activated protein kinase (MAPK). Activated MAPK is transported to the nucleus where it phosphorylates cAMP responsive element binding protein (CREB). Phosphorylation causes activation of CREB that leads to expression of early downstream genes such as tissue-type plasminogen activator (tPA) and brain-derived neurotrophic factor (BDNF) etc. Phosphorylation of CREB cause increased immediate early gene or IEG transcription factor. Binding of IEG to DNA activates late genes that are involved in structural proteins, enzymes, ion channels, and neurotransmitters. This cause short term signals to be converted to long-term Potentiation signals. IEG activate tPA, which decomposes plasminogen to plasmin. Plasmin converts precursor proBDNF to the mature BDNF (mBDNF), which is required for LTP in hippocampus.

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