|Born to Forget: Silent Neurons in Dentate Gyrus||Memory|
"Forgetting" may result from two possibilities: (1) the physical memory traces have gone forever, and (2) the memory still exists but could not be recalled at a given moment. The AMPAR endocytosis is an example of the first possibility. In this case, the memory is said to be "erased". Memory extinction refers to the second case. Its underlying mechanism is the focus of this book.
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, namely, 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). As discussed extensively in subsequent chapters, the neuronal silence could be caused by tubulin inhibition of NMDA receptors (NMDARs). Hence, an NMDAR may have a new state in which the receptor is inhibited by tubulin. This novel state will be called the "extinction state", as it can give rise to the macroscopic memory extinction. Biophysically, the extinction state of an NMDAR resembles the inactivated state of a sodium channel (Yu and Catterall, 2003).
Author: Frank Lee