Glial Theory of Memory
According to this concept, the formation of long-term memory directly depends on the functional activity of glial cells closely surrounding brain neurons. Glia do not merely provide structural support, but specifically "program" the function of nerve cells during learning.
Key mechanisms of glial regulation:
- Metabolic changes: During learning, the concentration of ribonucleic acid (RNA) significantly increases in glial cells.
- Synthesis of active compounds: Glia begin to produce specific compounds that affect neurons. These substances can alter the baseline excitability of nerve cells and significantly facilitate signal transmission across synapses.
- Myelination: According to A.I. Roitbak's hypothesis, the depolarization of neuronal membranes stimulates their active myelination by glial cells. This insulates the fiber and multifoldly increases the efficiency of nerve impulse conduction.
Mediator Theory: The Role of Neurotransmitters
This theory is based on the premise that memory is inextricably linked to dynamic changes in synapses and shifts in the balance of neurotransmitters. Each neurotransmitter system performs its specific task.
Cholinergic System Acetylcholine is critically important for memory. Learning leads to an increase in the number of cholinergic receptors in central nervous system synapses. Microiontophoresis demonstrates that neuronal sensitivity to acetylcholine increases accordingly. Activation of these synapses triggers conformational changes in the postsynaptic membrane, increasing conductivity. Administering acetylcholine antagonists impairs learning and information retrieval, potentially leading to amnesia.
Noradrenergic System Norepinephrine responds sensitively to the type of reinforcement. Under painful (electrocutaneous) reinforcement, noradrenergic mechanisms are activated, whereas under food reinforcement, brain norepinephrine levels decrease. Pharmacological deficit of this neurotransmitter causes amnesia, slows down learning, and hinders the retrieval of already formed memory traces.
Serotonergic and Dopaminergic Systems Dopamine performs a general modulatory function in memory mechanisms. Serotonin is responsible for memory consolidation (transition from short-term to long-term memory). According to E.A. Gromova, the serotonergic system is particularly active during learning accompanied by emotionally positive reinforcement.
Molecular Cascade and Memory Stabilization
The formation of long-term memory requires structural consolidation. Monoaminergic systems trigger a complex intracellular molecular cascade:
- Intracellular postsynaptic processes are activated first.
- Second messengers—cyclic nucleotides (cAMP and cGMP)—enter the reaction.
- Under their influence, metabolic pathways are activated, leading to the synthesis of specific protein molecules.
- The synthesized proteins integrate into synaptic membranes, stabilizing primary modifications. This is how the memory trace is reliably anchored in brain structures.
Synaptic Mechanisms and the Lynch-Baudry Concept
The foundation of any memory is the engram—the physical trace of a memory, represented by a zone of increased synaptic conductivity. Glutamic acid and gamma-aminobutyric acid (GABA) actively participate in this process.
The detailed molecular mechanism of engram formation is described by the G. Lynch and M. Baudry concept:
- Upon repetitive neuronal stimulation, the concentration of calcium ions ($Ca^{2+}$) in the postsynaptic membrane area increases sharply.
- Calcium activates a specific enzyme: calcium-dependent protein kinase.
- This enzyme cleaves one of the structural proteins of the postsynaptic membrane.
- As a result of cleavage, glutamate receptors that were previously inactive are "unmasked" (released).
- The total number of active receptors increases, leading to a sustained increase in synaptic conductivity.