|Memory > Born to Forget: Silent Neurons in Dentate Gyrus|
"Forgetting" could arise from two possibilities: (1) the physical memory traces have gone forever, or (2) the memory still exists but its retrieval is inhibited. In the first case, the memory is said to be "erased". Memory extinction refers to the second case, namely, the inhibition of memory retrieval.
In experiments, memory extinction can be demonstrated by a procedure known as "extinction training". This procedure starts from a classical Pavlovian conditioning to associate a conditional stimulus (CS; e.g., a tone) with an unconditional stimulus (US; e.g., an electric shock for fear memory). After the association between CS and US has been established, presentation of the CS alone can initiate a conditioned response (e.g., defensive behavior or emotional reactions related to electric shock). Then, in the standard extinction training, the CS is repeatedly presented to the subject without pairing with US. This results in a gradual decrease in conditioned response, indicating that the memory is being forgotten (Dunsmoor et al., 2015). However, it tends to return, suggesting that the training procedure does not erase the memory, but simply suppresses its retrieval.
There are several types of memory. One of them is the autobiographical memory such as the events of birthday party, wedding ceremony etc. The autobiographical memory is also called "episodic memory", as it records an episode of life history. They are different from "semantic memory" which is about knowledge such as language and mathematics.
When we recall an event in our life history, we can know roughly when such event had occurred. The recently happened event can easily be distinguished from those that occurred many years ago. This indicates that somehow the autobiographical memories are kept in chronological order. The dentate gyrus (DG) could be empowered with such capacity. In an adult brain, only two regions are capable of generating new neurons. One of them is DG which continuously creates granule cells throughout life (Ming and Song, 2011). This feature may enable DG to encode time in new memories (Aimone et al., 2006).
In DG, more than 90% of granule cells are silent, that is, they do not respond to environmental stimuli. The active neurons are probably the newborn cells (Alme et al., 2010). This suggests that the newly generated cells are active only when they are young. During the juvenile period, they may participate in memory formation, and then become silent. The silent cells will no longer engage in memory acquisition, but they could be activated by the cues that induced the old memory (see next chapter). In subsequent chapters, evidence will be presented to support the CABT hypothesis that neuronal silence could be caused by "NMDAR extinction", namely, the inhibition of NMDA receptors (NMDARs) by the CABT complex, which consists of a CRMP2 monomer, an alpha (α) and a beta (β) tubulin.
Author: Frank Lee