Role of Nucleic Acids in Learning
Nerve cells of the brain differ from other somatic cells not only by a record high RNA content, but also by a maximal number of active genes. To elucidate the precise biochemical mechanisms of memory, researchers used specific macromolecular synthesis inhibitors:
- Experiments with 8-azaguanine. This drug disrupts normal RNA synthesis by substituting guanine in the growing 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 expression. This proves that RNA is critically important specifically for the consolidation (encoding) phase of memory, rather than for its storage.
- Experiments on DNA inhibition. Researchers used the DNA synthesis inhibitor azidothymidine (AZT). It was demonstrated that blocking the DNA apparatus completely prevents the transition of a fresh memory trace from short-term memory to long-term memory.
Classic Experiments on Planarians
The first attempts to identify a physical 'molecular substrate' of memory were conducted on flatworms (Planaria).
- Worms were trained in a defensive reflex: pairing a light flash with a subsequent electric shock. Eventually, 100% of the subjects began to avoid the light.
- Trained worms were cut in half into head and tail portions.
- Both halves successfully regenerated into complete individuals.
- Upon testing, both new planarians retained the memory of the light and demonstrated the defensive response.
It was concluded that memory transfer depends on structural changes in every 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, only the individual that grew from the original head end retained the skill. This directly pointed to the decisive role of specific RNA molecules.
Microchemical Analysis and H. Hydén's Hypothesis
The Swedish researcher H. Hydén used ultra-fine micromethods to isolate individual neurons and assess their intracellular RNA levels.
In one experiment, rats were forced to balance on a stretched wire, which strongly activated the vestibular system. Trained animals showed a sharp increase in RNA concentration in neurons of the Deiters vestibular nucleus (lateral vestibular nucleus). In other tests (rats reaching for food with a specific paw), an increase in RNA content was noted in the motor cortex and adjacent glial cells.
Based on these data, Hydén formulated a hypothesis:
- Specific neural impulse activity affects the neuron.
- This causes a rearrangement of nitrogenous bases within the RNA structure.
- 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 neural impulses.
The Problem of 'Chemical Memory Transfer'
At one time, experiments by McConnell, who fed tissues of previously trained planarians to untrained conspecifics, generated widespread interest. Surprisingly, the latter began demonstrating a defensive response to light without any prior training.
Attempts were made to extend similar experiments to mammals. Untrained rats received intraperitoneal injections of purified RNA or brain extracts from their trained counterparts. Several authors reported improved learnability and reduced skill-acquisition time in recipient rats. Furthermore, when it turned out that RNA-free extracts also produced a similar effect, the concept of 'memory proteins' emerged.
Criticism: Despite the sensational nature of these findings, they are now considered unreliable. Numerous independent laboratories failed to reproduce these transfer effects. Today, it is generally accepted that the administration of brain extracts did not cause a targeted transfer of a specific skill, but merely a nonspecific increase in motivation and overall excitability of the animal's nervous system.