Semantron 23 Summer 2023

Learning and memory

response increases for an extended period of time (up to a couple of weeks, essentially how long you may remember that piece of information for). This process is known as long-term potentiation (LTP), and is considered to be a major basis in learning and memory. It was famously observed in the hippocampus, resulting in a landmark paper published in 1973 by Bliss and Lømo, and it has subsequently been observed within other areas of the association cortices, which are so crucial to our humanity. Essentially, as the presynaptic neuron is stimulated, the neurotransmitter glutamate is released into the synapse and binds to the α -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (or AMPA receptor for short) of the postsynaptic neuron. This receptor is paired with a sodium ion channel, and upon binding with glutamate, allows sodium ions to diffuse into the postsynaptic neuron, causing the dendrite of the postsynaptic neuron – the point at which this AMPA receptor is present and where sodium ions will enter into – to be locally depolarized. Upon reaching the critical threshold for an action potential, the action potential will travel down the neuron and to the next neuron. However, N-methyl-D-aspartate (NMDA) receptors bound to calcium ion channels are also present on the postsynaptic neuron. At resting potential, these receptors are blocked by magnesium ions, but upon depolarization, the magnesium ions are expelled from the ion channels, allowing the diffusion of calcium ions into the postsynaptic neuron. These calcium ions activate many enzymes within the postsynaptic neuron, such as calmodulin, which becomes Ca2+/calmodulin upon binding with 4 calcium ions, which then activates other enzymes such as adenylate cyclase and Ca2+/calmodulin-dependent protein kinase II (CaM kinase II). These two enzymes play key roles in LTP by modifying the structure of other molecules by adding a phosphate ion (this is known as phosphorylation). CaM kinase II phosphorylates AMPA receptors, NMDA receptors and other proteins such as mitogen-activated protein kinases (MAP kinases) which are involved in dendrite construction. The phosphorylation of the AMPA receptors allows them to remain open long after having bound to glutamate, further depolarizing the postsynaptic neuron and contributing to LTP, calcium ion conductance increases in a similar way with NMDA phosphorylation and speed of dendrite construction by MAP kinases increases, as phosphorylation is a catalytic process. Additionally, CaM kinase II has the unique property of being able to phosphorylate itself, and so its enzymatic activity continues long after calcium is released from the postsynaptic neuron and Ca2+/calmodulin has been deactivated, helping to put the LT (long-term) in LTP (long-term potentiation). Adenylate cyclase, on the other hand, synthesises cyclic adenosine mono- phosphate (cAMP) which catalyse protein kinase A (PKA) enzymes. This PKA causes numerous effects, many of which have likely not been discovered. One effect is that PKA phosphorylates also phosphorylates AMPA receptors, but another is that PKA phosphorylates cAMP response element-binding proteins (CREB proteins), which play major roles in gene transcription and lead to the synthesis of new AMPA receptors, further increasing postsynaptic sensitivity. This all leads to the depolarization of the postsynaptic neuron becoming easier and easier as the presynaptic neuron is stimulated, allowing for certain neuronal connections to be prioritized over others as priority neurons are stimulated. And as these effects persist after stimulation, this results in the phenomenon of memory where the information we have learned via the pathways of neuronal stimulation is more easily accessible and recallable as the neuronal pathways are more easily stimulated by the increased ease of neuronal depolarization.


Made with FlippingBook - Online catalogs