Effect of ablated hippocampal neurogenesis on the formation and extinction of contextual fear memory

Abstract

Newborn neurons in the subgranular zone (SGZ) of the hippocampus incorporate into the dentate gyrus and mature. Numerous studies have focused on hippocampal neurogenesis because of its importance in learning and memory. However, it is largely unknown whether hippocampal neurogenesis is involved in memory extinction per se. Here, we sought to examine the possibility that hippocampal neurogenesis may play a critical role in the formation and extinction of hippocampus-dependent contextual fear memory. By methylazoxymethanol acetate (MAM) or gamma-ray irradiation, hippocampal neurogenesis was impaired in adult mice. Under our experimental conditions, only a severe impairment of hippocampal neurogenesis inhibited the formation of contextual fear memory. However, the extinction of contextual fear memory was not affected. These results suggest that although adult newborn neurons contribute to contextual fear memory, they may not be involved in the extinction or erasure of hippocampus-dependent contextual fear memory.

Sonic hedgehog signaling regulates amygdalar neurogenesis and extinction of fear memory

“…Previous studies in hippocampus have shown that ablation of neurogenesis in mice by γ-irradiation or anti-mitotic agent failed to affect the extinction of contextual Amygdalar neurogenesis and extinction H.C. Hung et al 22 fear memory (Ko et al, 2009) and avoidance response (Burghardt et al, 2012).…”

Learning not to Fear: Neural Correlates of Learned Safety

“…As such, the observed increased levels of hippocampal BDNF and augmented hippocampal neurogenesis (Pollak et al, 2008) are very probable candidate mechanisms mediating this contextual flexibility at the molecular level. Interestingly, also during fear extinction, specifically the extinction of contextual fear, where the hippocampus is most importantly involved in the retrieval of extinction memory (see for a review Quirk and Mueller, 2008), both hippocampal neurogenesis (Cleva et al, 2011;Deng et al, 2009;Ko et al, 2009;Pan et al, 2012) and BDNF expression (Andero and Ressler, 2012;Heldt et al, 2007;Liu et al, 2004) are required for its behavioral effects. As for recall of fear extinction, a critical role for BDNF expression has also been demonstrated in the rat BLA, where fear extinction learning also induced upregulation of its mRNA (Chhatwal et al, 2006), an intriguing observation that has not yet been tested for learned safety.…”

Reduced abnormal integration of adult-generated granule cells does not attenuate spontaneous recurrent seizures in mice

“…The DNA methylating agent methylazoxymethanol acetate, a toxin for proliferating cells, was demonstrated to be highly effective in ablation of hippocampal neurogenesis (Shors et al, 2001;Ko et al, 2009). More importantly, hippocampal neurogenesis will recover a few weeks after the ablation (Shors et al, 2001).…”