Unraveled the secret of long-term memory

March 22, 2012 8:42

Unraveled the secret of long-term memoryLong-term memory — A mysterious phenomenon. Its mechanism is fundamentally different from fosfrilirovaniya proteins occurring in the short-term memory. American scientists have made an unexpected conclusion: this process is related to the transition of a specific protein in amyloid CPEB condition that is commonly associated with severe disease.

Long-term memory — a phenomenon in principle mysterious. Detailed studies have shown that the duration of storage memory is divided into three stages: sensory memory (trace excitation of sensory divisions of the nervous system), short-term and long-term memory. Sensory, or primary memory lasts fractions of a second and is the primary processing of sensory information — audio, visual, tactile, and so on and further analysis.

Actually, it's not even the memory as such, but a touch-trace perceived body incentives. But this track lasts longer than the actual impact of a stimulus, because of delays and switching in the central nervous system.

Material selected for storage, fixed in the secondary or short-term memory. Its biochemical mechanism involves the phosphorylation of several proteins in neurons. Phosphorylation occurs in response to their stimulation, which leads to a change in strength of synapses. As modified proteins derived from the circulation, the event is forgotten — unless there is a "conversion" of short-term memories into long-term memory.
It is long-term or tertiary memory provides the firm retention of information. Memories are "encoding" in the presence of motivation, strong emotional coloring or regular repetition. Obviously, the mechanism of long-term memory is fundamentally different from fosfrilirovaniya (sewing phosphoric acid) proteins. Biochemical process in this case must be based on the change in the neurons, which may persist for a long time, sometimes — for the entire life of the organism. But which one?

Unraveled the secret of long-term memoryA few years ago, scientists have hypothesized that this change is a shift in the state of amyloid protein CPEB (Orb2 in Drosophila). Recently, this hypothesis was confirmed.

First of amyloids in the scientific world were associated mainly with the negative developments. They were known as the pathological protein structures, causing a large group of so-called amyloid diseases: Alzheimer's disease, Parkinson's, and prion diseases — Neurodegenerative diseases associated with the accumulation in the body of prions, the infectious agents of protein nature.

Amiolidy themselves represent a certain fibrillar polymers normally soluble cellular proteins. They catalyze structural change and adherence to their monomers of the same protein, and thereby grow. These substances can be contagious, in which case they just called a prion.
Infectivity due to their property just catalyze restructuring. In human and animal prions associated with only one protein — PrP, and cause mad cow disease, scrapie ("scrapie) sheep and Creutzfeldt-Jakob disease in humans.

Phenomenon similar prion was found in ordinary baker's yeast Saccharomyces cerevisiae. They prion diseases are not, in their case, it is a rare phenotype with a fancy way of inheritance, different from the traditional laws of Mendel. Yeast prions arise spontaneously and quite rare. But later can be saved in a number of generations, and the crossing passed to all children.

Thus, prionogenny protein can stably exist in two states: prions (polymerize) or normal. Scientists conducted an analogy: a cage with prionogennym protein can be expressed as one-bit memory cell.
The neurons previously often been studied in the sea hare — allizii mollusk (Aplysia californica): it has a large, easy to study neurons. Detailed studies of the neurons allizii shown that long-term memory requires protein CPEB (cytoplasmic polyadenylation element binding protein). This protein activates the transcription of messenger RNAs that are required to memorize. (Long-term memory requires the synthesis of new mRNA and protein, and is often accompanied by the establishment of new synaptic connections).

To the surprise of scientists, its structure was similar to the CPEB yeast prion proteins. The similarity of these proteins is that each has two parts: the functional domain and the prion domain that can polymerize. Functional domains in CPEB and yeast prion proteins are quite different, and prion domains have a common property — they are not structured and highly enriched amino acid residues of glutamine and asparagine.

It allows the prion domains polymerize amyloid fibrils. CPEB properties tested in a yeast model, and found that it behaves like a normal yeast prion: able to enter stably heritable polymeric state.
To conclusively establish the long-term memory due to the transition state of the protein amyloid, American biologists have conducted studies on Drosophila. Unlike allizii, Drosophila has two choices protein SREV: Orb2A and Orb2B, which are derived from the same mRNA. Orb2B protein synthesized continuously, and Orb2A — only in response to stimulation of the neuron.

Scientists have suggested that the stimulation of neuronal synapses in Drosophila synthesized Orb2A. He goes into the state of the polymer and leads the Orb2B. The process is further supported by the polymerization Orb2B molecules and can last any length of time, which corresponds to fixing the events in long-term memory.

To test the hypothesis, biologists conducted mutagenesis and protein Orb2A have mutations that violate its ability to initiate the polymerization., And then conducted a test that detects the work of memory in flies with and without the mutation. The experiment was allowed to try Drosophila droplets of water, plain or with sugar, bearing different scents.

Biologists then checked how long the flies can choose "tasty", a sweet drop of the smell. In flies with a mutation Orb2A short-term memory was working fine, but the long-term have been broken — they have the association was confined for two days. In another experiment, the male fruit fly repeatedly presented with "unresponsive" female, already last pairing.

Learned from bitter experience, usually a male forever razuverivalsya in women did not begin courting, meeting another female. A mutant male forgot his grief after about two days
Tests confirmed that mutation, breaking polymerization Orb2, violates and long-term memory. According to scientists, the nerve cells were able to "tame" the amyloids. Extremely important is the fact that the cell, as it turned out, could manage the transition to the amyloid state. However, take a synapse of this condition is likely impossible, to the scientists. "Erase and rewrite the" long-term memory can not. According to experts, the brain seems to be compared to a device such as a write-once CD-ROM, but not with the drive.

Ian Filimonov

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