6.5Memory and Long-Term Potentiation

During surgery of an epilepsy patient, it was found that an area called the hippocampus in the limbic system of the cerebrum is involved in memory. Since the symptoms of the disease were severe, the hippocampus of this epilepsy patient was surgically excised. The patient could remember events from the distant past but not recent events. This indicates that the hippocampus is important for memory. There are different types of memory: procedural memory, which is learned by the body, such as riding a bicycle; and declarative memory, which requires conceptualization. The hippocampus is vital for declarative memory.
If neurons of the hippocampus are stimulated many times at a high frequency, the response of the nerves receiving the stimulus becomes stronger. Once the response becomes stronger, it remains strong for several weeks. This phenomenon is called long-term potentiation (LTP). During LTP, spines like briars protrude from the postsynaptic membrane. This phenomenon shows that when neurons are stimulated for a short time at a high frequency, their neurotransmission becomes more effective. This is now considered the prototype of memory (Fig. 6-10).
It has been discovered that long-term potentiation occurs when glutamic acid receptors in neurons are blocked, and that glutamic acid is an important neurotransmitter for memory. Humans have three types of glutamic acid receptors. Receptors with high sensitivity to a substance called N-methyl-D-aspartic acid (NMDA) in particular are known to be involved in memory.

Fig. 6-10 Long Term Potentiation (LTP)


The Relationship between NMDA Receptors and Memory

NMDA receptors are membrane proteins consisting of the two molecules NR1 and NR2. Throughout the development of an organism, NR2 changes from fetal-type NR2B to adult-type NR2A. However, NMDA receptors that have NR2B are more efficient in terms of receptor channel function. In other words, as far as the genes of higher animals like us are concerned, our memory is genetically programmed to deteriorate as we reach adulthood.
Memories of mice that were created to overexpress NR2B are several times better than that of normal mice. Therefore, NR2B is called a smart gene. On the other hand, mice with non-functioning NR1 genes have poorer memories than normal mice. However, if such mice are not raised individually in cages, but are raised together with other mice in a spacious environment where they can play, their memories improve remarkably. Thus, increased memory requires not only genes but also environmental conditions.
However, memory is not determined by only one gene; several other genes have been discovered whose knockout mice show memory disorders.

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