Possible modulation of the amygdala on metaplasticity deficits in the hippocampal CA1 field in early postnatally stressed rats.

Several lines of evidence have shown that early life experiences have a profound impact on fear-related behavior, but the detailed mechanisms are unknown. The present study examined the possible involvement of the amygdala in behavioral deficits associated with fear memory in a juvenile stress model, with a focus on hippocampal synaptic function. Adult rats exposed to footshock (FS) stress during the second postnatal period (2wFS group) exhibited low levels of freezing in response to contextual fear conditioning (CFC). The CFC-induced suppression of long-term potentiation (LTP) in the CA1 field was not found in the 2wFS group. Additionally, synaptic metaplasticity, that is, low-frequency stimulation-induced suppression of subsequent LTP, did not occur in the 2wFS group; instead, LTP was induced. These synaptic changes mimicked the impairment in metaplasticity induced by reversible inactivation of the basolateral amygdala (BLA). Inactivation of the BLA markedly decreased freezing behavior in non-FS controls, similar to the 2wFS group. Furthermore, extracellular signal-regulated kinase activation in the BLA in response to CFC did not occur in the 2wFS group. These findings suggest that early postnatal stress may cause long-term dysfunction of the modulatory effect of the amygdala on hippocampal function associated with fear memory.