Biological Chemistry - Berezov, T. T., Korovkin, B. F. 1998

Nervous Tissue
Chemical Basis of the Generation and Conduction of Nerve Impulses
Mechanisms of Memory

Memory is not concentrated in a single, strictly localized area of the Brain, unlike the centers for Vision, Hearing, speech, and so forth. At the same time, memory is not a property of the brain as a whole. The biological substrate of human memory is Neurons.

Human memory cannot be considered in isolation from human activity, because it is not cognition that cognizes, nor thinking that thinks, nor memory that memorizes and recalls; rather, it is the human being—an individual personality—who cognizes, thinks, memorizes, and recalls.

In recent years, it has been clearly demonstrated that training animals in new skills affects the chemistry of brain Cells (neurons): changes occur in The amount of uridine in cytoplasmic RNA, the degree of DNA Methylation, and the phosphorylation of Nuclear Proteins. The administration of stimulants and RNA precursor substances facilitates learning, whereas the Introduction of RNA Synthesis blockers, conversely, hinders this process. Evidence also suggests that the antigenic composition of brain tissue changes following the memorization of information. It is customary to distinguish several forms of biological memory: genetic, immunological, and neurological. The BIOCHEMICAL FOUNDATIONS OF genetic memory are more or less clear, with cellular DNA serving as its carrier. Immunological memory represents the next level of complexity; although it incorporates ELEMENTS OF GENETIC memory, it occupies a higher evolutionary tier. Finally, the neurological memory system is even more complex. This form, in turn, can be divided into short-term memory (STM) and long-term memory (LTM). STM is presumably based on the "Circulation" of information, received as impulses, through closed neuronal circuits. Furthermore, synaptic effects, alterations in the nucleolar apparatus, the release of BIOLOGICALLY ACTIVE SUBSTANCES into the neuron's Cytoplasm, and the accompanying metabolic restructuring of The Cell can all be regarded as indicators of STM functioning.

The activation of LTM blocks occurs approximately 10 minutes after information enters the cell. During this time, the biological Properties of the nerve cell undergo reorganization. A number of researchers believe that afferent impulsation arriving at Nerve Cells during learning either induces a quantitative upregulation of RNA and Protein Synthesis—potentially leading to the establishment of new synaptic connections and the remodeling of existing ones—or that this activation of nucleic acid and Protein synthesis is targeted and specific, with the synthesized molecules acting as a repository of information.

The Role of Neurotransmitters in The regulation of memory. Memory processes are closely linked to the modification of synthetic pathways; therefore, chemical Transmitters of nerve impulses must play a fundamental role in this regard. A substantial body of experimental data has been accumulated concerning The Significance of neurotransmitters in memory and learning processes. Results obtained to date indicate the vital importance of major neurotransmitters (acetylcholine, norepinephrine, dopamine, serotonin, GABA) in these processes, although the specific contribution of each transmitter depends on the particular type of information being memorized. For instance, it has been shown that a decrease in brain acetylcholine levels caused by Choline acetylase inhibitors impairs learning, whereas its elevation accelerates the acquisition of defensive skills. Serotonin facilitates the acquisition and retention of skills based on positive (alimentary) reinforcement while exerting a negative effect on The formation of defensive reactions. According to current concepts, the noradrenergic and serotonergic systems act largely as antagonists regarding memory processes, and the capacity to acquire specific skills depends less on the absolute level of a given neurotransmitter than on the activity ratio between these systems. Thus, impairments caused by elevated serotonin levels can be compensated for by the parallel activation of the noradrenergic system, and vice versa. It should also be noted that there is extensive evidence indicating a pronounced inhibitory effect of GABA on memorization and learning processes.

Oligopeptides as memory regulators. It has been established that certain oligopeptides—molecules consisting of a small number of amino acid residues—are capable of modifying the learning process and influencing the acquisition, retention, and extinction of acquired behavioral responses. Among Peptide Hormones, the most pronounced effects on Learning and Memory processes are exerted by Pituitary Hormones: adrenocorticotropic hormone (ACTH) and vasopressin. When studying METABOLISM/18.html">The Influence of ACTH on memory, it was shown that the primary role in its action belongs to the ACTH_4-10 fragment, which produces virtually the same effect on these processes as the intact hormone. Moreover, it was found that the stimulatory influence of ACTH fragments on learning is unrelated to the peptide's proper hormonal function, as these memory-activating fragments lack such activity.

Vasopressin, a posterior pituitary hormone, also exhibits a strongly pronounced positive effect on the acquisition of conditioned responses in animals. The stimulation of memory processes by vasopressin is not linked to its hormonal action, since a similar stimulatory effect is produced by certain analogs and fragments that do not trigger the hormonal responses typically caused by vasopressin. There is every reason to believe that ACTH and vasopressin, or their fragments generated in the body through hormone Cleavage, not only stimulate memorization when administered exogenously, but also function continuously in the brain as regulators of memory processes [Ashmarin et al., 1996].