The effects of acid-sensing ion channel-1A on conditioned fear memory are age-dependent

The neuronal circuits underlying Pavlovian fear conditioning have been suggested to undergo marked changes during brain development. One molecule that is expressed in the brain during early development and that plays a key role in fear learning and fear memory in adult mice is the acid-sensing ion channel-1A (ASIC1A). Therefore, this gene is well-positioned to influence Pavlovian fear conditioning across development. To explore this possibility, we used Pavlovian fear conditioning to probe the effect of Asic1a disruption on fear memory acquisition and on cued- and contextual fear memory recall throughout development. During fear memory acquisition, Asic1a ^-/- mice of all ages froze significantly less than Asic1a ^+/+ mice. Cue-evoked freezing tested 24 h after training was similarly reduced in Asic1a ^-/- mice trained at postnatal day 23 (P23) and later. Surprisingly, cue-evoked freezing was unimpaired in Asic1a ^-/- mice trained at P17. However, context evoked freezing was largely impaired across development, implying cue and context freezing are dissociable at P17. To our knowledge this is the first report of age-dependent behavioral effects with loss of ASIC1A. The emergence of cue-evoked memory deficits in Asic1a ^-/- mice between P17 and P23 coincides with the extensive developmental alterations the fear circuit undergoes during this time window. The increasing deficit in fear memory with age in Asic1a ^-/- mice further suggests a role for ASIC1A in the maturation or function of circuits relevant to Pavlovian fear conditioning.