Memory  >   Memory Consolidation: The Memory Engram Network

A memory does not reside in a small brain area. Rather, it is represented by a large population of neurons distributed over the brain (Herry and Johansen, 2014). The neurons involved in the storage of long-lasting memories are referred to as "memory engram cells", which could be the spiny neurons located in the cerebral cortex, hippocampus, basolateral amygdala, and striatum (Chapter 7). This chapter will discuss the interconnection among the brain areas that form the memory engram network.


Figure 31-1. Connections of the brain areas that form the memory engram network. EC, entorhinal cortex; DG, dentate gyrus; SUB, subiculum; Amy, amygdala; NAcc, nucleus accumbens; RE, nucleus reuniens; mPFC, medial prefrontal cortex. [Adapted from: Jin and Maren, 2015]

There are direct monosynaptic and indirect multisynaptic connections between the hippocampus and medial prefrontal cortex (mPFC). This pathway plays an important role in working memory, episodic memory and emotional memory. In particular, mPFC receives strong glutamatergic input from CA1 (Jin and Maren, 2015). mPFC also projects directly to the CA3/CA1 region (Rajasethupathy et al., 2015). Other areas are also interconnected (Figure 31-1). Hence, activation of mPFC memory units may induce activation of the memory units in other brain areas. This may explain why optogenetic stimulation of the anterior cingulate cortex (ACC, located in mPFC) is sufficient to induce contextual memory retrieval (Rajasethupathy et al., 2015). Stimulation of the dentate gyrus also suffices to retrieve fear memories (Liu et al., 2012), despite the fact that memories are stored in distributed brain areas.

Optogenetic Stimulation may Overcome NMDAR Extinction

During natural physiological operation, reactivation of the memory units in a silent engram cell requires two conditions: (1) recovery from NMDAR extinction (i.e., dissociation of CABT from NMDAR), and (2) a substantial glutamate pond. However, the silent engram cells can also be activated artificially by optogenetic method which incorporates light-sensitive cationic channels (e.g., channelrhodopsin-2) to depolarize the membrane (Liu et al., 2012; Ryan et al., 2015). The artificially added cationic channels more than compensate for the inhibition of NMDARs by the CABT complex. In the paper of Roy et al. (2017), the term "silent engram cells" is defined as the engram cells that can be activated by optogenetic stimulation, but not by natural recall cues. This definition is not the same as the one used here. According to the definition on this website, an engram cell has various degrees of silence, depending on the proportion of NMDARs in the extinction state. Mildly silent engram cell can be activated by natural recall cues as demonstrated experimentally (see Chapter 11). Severely silent engram cells, such as those involved in infantile amnesia, cannot be activated by natural recall cues.


Author: Frank Lee
First published: July, 2018