The Role of Nucleic Acids in Learning
Brain nerve cells differ from other cells in the body not only by a record-breaking RNA content, but also by the maximum number of active genes. To precisely determine the biochemical mechanisms of memory, scientists used specific macromolecular synthesis blockers:
- Experiments with 8-azaguanine. This drug disrupts normal RNA synthesis by substituting for guanine in the forming chain. Administration of this substance significantly impairs the formation of new conditioned reflexes. However, if the drug is administered after the skill has already been formed, it has no effect on its manifestation. This proves that RNA is critical specifically for the consolidation (formation) stage of memory, rather than for its storage.
- K.V. Anokhin's experiments. The researcher used a DNA synthesis blocker, azidothymidine. It was found that blocking the DNA apparatus completely prevents the transfer of a fresh trace from short-term to long-term memory.
Classic Experiments on Planarians
The first attempts to find the physical "molecular substrate" of memory were carried out on flatworms—planarians.
- The worms were trained in a defensive reflex: a light flash was paired with a subsequent electric shock. As a result, 100% of the individuals began to avoid the light.
- The trained worms were cut in half: into head and tail parts.
- Both halves successfully regenerated into full-fledged individuals.
- Upon testing, it turned out that both new planarians retained the memory of the light and demonstrated a defensive reaction.
It was concluded that memory transfer depends on structural changes in each cell of the trained organism. To confirm the role of RNA, the enzyme RNase (which degrades RNA) was added to the medium where the worms were regenerating. In this case, the skill was retained only by the individual that grew from the original head end. This directly indicated the decisive role of specific RNA molecules.
Microchemical Analysis and H. Hydén's Hypothesis
Swedish researcher H. Hydén used delicate micromethods to isolate individual neurons and assess the level of RNA within them.
In one of the experiments, rats were forced to balance on a tightrope, which strongly activated the vestibular apparatus. In trained animals, a sharp increase in RNA concentration was recorded in the neurons of Deiters' vestibular nucleus. In other tests (rats retrieving food with a specific paw), an increase in RNA amount was noted in the motor cortex and adjacent glial cells.
Based on these data, Hydén formulated a hypothesis:
- Specific neural impulse activity acts on the neuron.
- This causes a rearrangement of nitrogenous bases in the RNA structure.
- The altered messenger RNAs trigger the synthesis of new, specific proteins.
- The appearance of these proteins makes the neuron selectively sensitive to a strictly defined configuration of nerve impulses.
The Problem of "Chemical Memory Transfer"
At the time, McConnell's experiments caused a huge resonance; he fed the tissues of pre-trained planarians to untrained "relatives". Surprisingly, the latter began to demonstrate a defensive reaction to light without any training.
Attempts were made to replicate such experiments in mammals. Untrained rats were intraperitoneally injected with purified RNA or brain extracts from their trained conspecifics. A number of authors reported improved learning ability and reduced skill formation time in recipient rats. Moreover, when it turned out that extracts without RNA also produced a similar effect, the concept of "memory proteins" emerged.
Criticism: Despite their sensational nature, these results are now considered unreliable. Numerous independent laboratories failed to reproduce the transfer effects. Today, it is generally accepted that the administration of brain extracts did not cause targeted transfer of a specific skill, but merely a non-specific increase in motivation and general excitability of the animals' nervous system.
Briefly: answers to topical questions
What is the role of secondary messengers (cAMP, calcium ions) in triggering gene transcription during memory formation?
Secondary messengers trigger a cascade of biochemical reactions that ensure signal transduction to the cell nucleus and genome activation. The convergence of stimuli on the neuron membrane activates secondary messengers, which translate the signal into the nucleus. This leads to early gene expression and the initiation of transcription (RNA synthesis on a DNA template). Subsequently, translation occurs, and the synthesized specific proteins are incorporated into synaptic membranes, ensuring long-term plasticity and engram formation. Specific types of secondary messengers are not detailed in the texts.
What other brain structures, aside from the motor cortex and vestibular nuclei, play a key role in the molecular consolidation of memory?
In addition to the motor cortex and Deiters' vestibular nucleus, sources directly link memory fixation and consolidation primarily to the hippocampus.
- The hippocampus ensures memory consolidation—the transition of short-term memory into long-term memory; in neuropsychological studies, it is assigned the primary role in fixing conscious memory. Damage to it or its associated structures causes amnestic syndrome, loss of old skills, difficulty in forming new skills, and short-term memory deficits.
- The temporal cortex of the cerebral hemispheres, along with the hippocampus, is associated with forgetting processes; upon damage to these structures, acquired skills are lost very quickly, which is linked to impaired memory consolidation.
- For emotional memory, sources describe the Papez circuit: hippocampus → mamillary bodies of the hypothalamus → anterior thalamus → cingulate gyrus → hippocampus. This circuit is indicated as an example of cortico-subcortical reverberation underlying emotional memory.
To memorize blockers: Azaguanine disrupts the Alphabet of RNA (substituting guanine, blocking memory production), while Azidothymidine halts Archiving (DNA synthesis and transition to long-term memory).
Class and exam questions
Does the blockade of RNA synthesis affect already established reflexes?
No. If an RNA blocker (e.g., 8-azaguanine) is administered after the reflex has already been established, the skill will be preserved and manifested. RNA synthesis is critical only for the process of formation (consolidation).
Why were the results of experiments with rat brain extracts criticized?
Most third-party laboratories were unable to reproduce these sensational results. It turned out that extract injections do not transfer memory itself, but merely increase the animal's overall motivation and excitability, accelerating its learning.
What is the role of glial cells in the molecular theory of memory?
Glial cells work in close conjunction with neurons. Experiments have shown that during motor skill learning, the amount of synthesized RNA increases not only in the motor cortex, but also in adjacent glial elements.
What else to study on this topic
- Role of Deiters' vestibular nucleus in H. Hydén's experiments
- Mechanism of action of RNAse on memory regeneration in planarians
- Evolution of views: from RNA molecules to the concept of specific "memory proteins"
- Differentiation of specific skill transfer and nonspecific motivation enhancement
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