Which Neurons Will Be the Engram - Activated Neurons and/or More Excitable Neurons?

Abstract

During past decades, the formation and storage principle of memory have received much attention in the neuroscience field. Although some studies have attempted to demonstrate the nature of the engram, elucidating the memory engram allocation mechanism was not possible because of the limitations of existing methods, which cannot specifically modulate the candidate neuronal population. Recently, the development of new techniques, which offer ways to mark and control specific populations of neurons, may accelerate solving this issue. Here, we review the recent advances, which have provided substantial evidence showing that both candidates (neuronal population that is activated by learning, and that has increased CREB level/excitability at learning) satisfy the criteria of the engram, which are necessary and sufficient for memory expression.

Keywords: CREB; Memory allocation; Memory engram; Review; excitability.

Fig. 1. Strategies and results for testing the necessity and sufficiency of the neuronal population, which is activated by learning. (A) Activated neurons during conditioning are marked by ArchT through gene expression control techniques. If this population is necessary for memory, the expression of fear memory associated with a context will be reduced by optogenetic silencing of this population. A reduced fear response by yellow light shows the necessity of the activation of this activated neuronal population for memory expression. (B) Activated neurons during conditioning are marked by ChR2 through gene expression control techniques. If this population is sufficient for memory, an artificial activation of this neuronal population will elicit a fear response in the neutral context. An induced fear response by blue light in neutral context shows the sufficiency of this activated neuronal population for memory expression.

Fig. 2. Strategies and results for testing the necessity and sufficiency of the neuronal population, which have high CREB level/excitability during learning. (A) If the neurons having a high CREB level and excitability are required to express the encoded memory, the expression of the fear memory associated with tone will be suppressed by induced cell death of these high CREB/excitability neurons. A reduced fear response after the targeted cell death of these high CREB neurons by inducible diphtheria-toxin strategy shows the necessity of the high CREB level neurons. (B) If the neurons having a high CREB level and excitability are sufficient to express the encoded memory, the activation of these neurons will be sufficient to elicit the fear response. An induced fear response using TRPV1/capsaicin system shows the sufficiency of the high CREB level neurons for the expression of fear memory.