Genes 2 Brains 2 Mind 2 Me

Image via Wikipedia Many of the unpleasant feelings and physiological changes associated with fear and anxiety can be traced back to a tiny brain region known as the amygdala. Neuroimaging studies often find this region abnormally active in people having difficulty down-regulating negative emotions. It is no surprise then, that when genes that regulate innate fear and the reactivity of this brain region are identified there is much hope for future medications that might target these biochemical pathways and relieve emotional suffering. So it is that Coryell and colleagues identify such a gene, ASIC1a, the acid sensing ion channel 1a, and report in their paper, “Targeting ASIC1a Reduces Innate Fear and Alters Neuronal Activity in the Fear Circuit” (DOI) and report that more expression of this gene results in mice with more innate fear and, that less expression or blockade of this gene results in less innate fear. The gene appears expressed in a well-studied fear circuit including the cingulate cortex, the amygdala and the bed nucleus of the stria terminalis, so any type of pharmacologic manipulation would be predicted to affect the entire fear circuit. The normal function of ASIC1a – a proton sensor – is presumably to regulate pH within and/or across cell membranes. Such changes in pH are known to affect synaptic transmission in a manner such that lower pH inhibits NMDA channels and higher pH activates NMDA channels, so it is possible that the effects of ASIC1a on fear may be ultimately due to effects on synaptic plasticity. An exciting candidate not to be feared.

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