To assess the physiological role of the gene, knockout (gene disruption) mice were developed. The null mice appear normal and reproduce normally, but show enhanced amygdala-dependent long-term memory consolidation with a concomitant elevation in amygdala, but not hippocampal, long-term potentiation (LTP). Hippocampal-dependent learning and motor skills appear normal, but mutant mice showed specific enhancement of amygdala-dependent learning of fear as assessed by cued (tone) conditioning and taste aversion protocols.

These findings represent a rare instance of elevated learning and memory that is localized and experimentally accessible to both in vitro and in vivo analyses, and is the only such case associated with fear and emotion learning. Mutations of this gene may be a contributing factor in human neuropsychiatric disorders characterized by increased excitatory activity in the amygdala or in amygdala dependent circuits. This gene, and reagents developed from it, should provide a useful model system for the development of therapeutic interventions.

Reference: UCLA Case No. 2002-133