|Why Can't We Recall Early Childhood Memories?||Memory|
It is virtually impossible for an adult to recall early childhood memories - the events that occurred earlier than 5 years old. This phenomenon is known as infantile amnesia (Travaglia et al., 2016), which may arise from the GluN2B-GluN2A switch during development.
Storage of Episodic Memory in Dentate Gyrus
In the dentate gyrus (DG) of the hippocampus, the same population of DG granule cells is activated repeatedly in the same environment, but different environments or different tasks activate different populations of DG granule cells (Liu et al., 2012), suggesting that an episodic memory is stored in a particular set of DG neurons. However, this does not mean that DG is the sole area to store episodic memories. Other areas are also involved (Herry and Johansen, 2014). Nonetheless, DG may play a unique role in the index and binding of memory information distributed over the brain. This notion is supported by the demonstration that activation of a set of DG neurons is sufficient to retrieve a particular fear memory (Liu et al., 2012).
The granule cells in DG are continuously generated throughout life. The newborn population is active only for a short period of time (Aimone et al., 2006). During the active period, the population may engage in memory acquisition and then become silent (Alme et al., 2010). The silent cells will no longer participate in memory acquisition, leaving the formation of new memory for another newborn population. Therefore, the DG granule cells that store childhood memories are different from those storing adult memories.
GluN2B-GluN2A Switch During Development
An NMDA receptor (NMDAR) consists of two GluN1 subunits and two additional subunits which are predominately either GluN2A or GluN2B. It has been well documented that the GluN2B/GluN2A ratio varies with the age of animals (including humans). In the hippocampus, the newborn animal expresses mostly GluN2B, with little GluN2A. As the animal grows older, GluN2B decreases while GluN2A increases (Dong et al., 2006).
Both tubulin and CRMP2 bind only to GluN2B, not GluN2A (Chapter 11). Therefore, the tubulin/CRMP2 complex can inhibit only the GluN2B-containing NMDARs, resulting in the "extinction state" (Chapter 11). The GluN2A-containing NMDARs do not have the extinction state. If a neuron expresses only GluN2A, it will never become silent. In contrast, a GluN2B-dominated neuron should be prone to silence. The degree of silence depends on the GluN2B/GluN2A ratio and other factors. Weakly silenced memory can easily be retrieved by reminding cues, but severely silenced neurons may not respond to any cue at all. Since the childhood DG neurons are dominated by GluN2B-containing NMDARs, they could be severely silenced by tubulin inhibition.
Author: Frank Lee