Geon Memory Extinction: The Role of BDNF Memory

 

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Figure 19-1. The location of the prelimbic and infralimbic subregions of the medial PFC in the rat and their equivalent regions in the human brain. [Source: Gass and Chandler, 2013]

BDNF infused into the infralimbic cortex is capable of inducing fear extinction (Peters et al., 2010). Infusion of BDNF into the dorsal mPFC attenuates reinstatement to cocaine-seeking behavior (Berglind et al., 2009), suggesting that the memory of cocaine-induced pleasure could be suppressed by BDNF. Furthermore, hippocampal-specific deletion of the BDNF gene significantly reduced extinction of conditioned fear (Heldt et al., 2007). Therefore, BDNF in both mPFC and hippocampus has the capacity to cause memory extinction. Recent studies have provided great insights into its mechanism.

In the cytoplasmic domain of the GluN2B subunit, there are three tyrosine residues (abbreviation: Y) which can be phosphorylated by Fyn or Src kinase. Phosphorylation at Y1472 prevents GluN2B-containing NMDARs from being internalized (Chen and Roche, 2007), consequently increasing their localization to the membrane. The membrane-bound GluN2B-containing NMDARs are subject to tubulin inhibition, which would hinder the generation of action potentials via NMDA plateau. BDNF has been shown to promote Y1472 phosphorylation (Xu et al., 2006), possibly through the BDNF/TrkB/Akt/Girdin/Src pathway (Nakai et al., 2014). This notion is supported by the finding that the Src family kinases are involved in the BDNF-mediated suppression of cocaine-seeking (Barry and McGinty, 2017).

Tet1 also plays an important role in memory extinction (Rudenko et al., 2013), but its actions could be mediated by BDNF. Tet1 is an enzyme that promotes DNA demethylation which is often used to regulate gene expression. Tet1 has been demonstrated to regulate the expression of the BDNF gene (Hsieh et al., 2016; Keifer, 2017).

 

Author: Frank Lee
First published: October, 2017
Last updated: January, 2018