Researchers at the Stowers Institute for Medical Research have come up with a scientific study that reveals a possible biochemical mechanism for creating and maintaining long-term memory. The Stowers’ research team had identified specialized brain cells called neurons that construct and sustain a long-term memory from a transitory experience.
The research appeared in the journal Cell. It is actually based upon previous studies by the scientists from Columbia University. According to these studies both short-term and long-term memories are created in synapses. Synapses are the tiny junctions between neurons that assist to conduct nerve impulses.
A transient experience is often a source of our great memories. Most importantly, it is capable of producing a long-term change in the strength of the synaptic connection. For the endurance of memory the synaptic connections must be kept strong. CPEB is a reported synaptic protein responsible for maintaining the strength of these connections. This protein was identified in the sea slug which is an often used model organism in memory research. In subsequent research at the Stowers Institute, the researchers identified Orb2 as the fruit fly version of the CPEB synaptic protein.
This respective research determines that Orb2 exists in two distinct physical states.
Monomeric Orb2 is a single molecule that potentially binds to other molecules. On the other hand, oligomeric Orb2, like CPEB, is prion-like. It is a self-copying cluster however; it isn’t like the disease-causing prions. Furthermore, oligomeric Orb2 and CPEB are not toxic in nature.
The activation and repression of Orb2
The research describes how monomeric Orb2 represses while the oligomeric Orb2 activates a crucial step in the composite cellular process, leading to protein synthesis. During this critical step, messenger RNA (mRNA) is translated by the cell’s ribosome into the amino acid sequence that will make up a newly synthesized protein. Note that mRNA is an RNA copy of a gene’s recipe for a protein.
The scientists propose that the monomeric form of Orb2 binds to the target mRNA. Furthermore, the bound mRNA is kept in a repressed state.
The scientists, conducting the respective study, also determined that prion-like Orb2 doesn’t activate translation only. It also imparts its translational state to nearby monomer forms of Orb2. As a result, monomeric Orb2 is transformed into prion-like Orb2. Consequently, its translational role switches from repression to activation. According to the researchers, this switch is the possible mechanism by which an organism develops enduring memories by a fleeting experience.
The research mentions that the self-sustaining nature of the prion-like state creates a local and self-sustaining translation activation of Orb2-target mRNA. This maintains the changed state of synaptic activity over time.
The discovery of the two distinct states of Orb2 and their opposing roles in the translation process provides a biochemical mechanism of synapse-specific persistent translation and long-lasting memory, for the very first time.
According to the researchers, this is the first example of a prion-based protein switch that turns a repressor into an activator. The recruitment of different protein complexes at the non-prion and prion-like forms create altered activity states. Thus, it indicates that prion-like behavior is, in essence, a protein conformation-based switch. This switch can cause a protein to lose or gain a function. Note that this transition can be maintained over time in the absence of the original stimuli.