Grant: CIHR Fellowship

Approximately 12% of Canadian adults suffer from some form of anxiety disorder. These illnesses are typified by inappropriate fear responses, often including the maladaptive generalization of fear, which occurs when fear elicited by one cue extends to other, similar cues, and can result in worsening anxiety in response to a large range of stimuli over time. Generalization is, at its core, a problem of signal specificity. Yet how it is regulated within the basolateral amygdala (BLA)-a key brain region in fear learning where associations between cues and outcomes are processed and stored-remains a largely open question. Among the BLA's numerous neuronal subpopulations, hyperplastic inhibitory interneurons (HINs) are unique in sharing many of the features that grant new, adult-born neurons the ability to rapidly integrate into memory circuits where they enhance signal specificity. In contrast to new neurons, however, existing evidence suggests that HINs may be able to de-mature/de-integrate from circuits as well, granting them an unparalleled level of flexibility. HINs may therefore be able to mimic the behaviour and function of new neurons even in regions that don't produce any. The purpose of this study is therefore to characterize how HINs in the BLA contribute to fear learning and generalization, and to explore how these cells are regulated at the molecular level. Using genetically-modified mice in which light can be used to activate or silence HINs in real-time (called optogenetics), we will be able to track changes in HIN structure, de-/integration, and gene expression as a function of both activity and the cue-specificity of learned fear. In addition to identifying how HINs are regulated and how they modulate BLA function, we expect this work to provide significant insight into the molecular control of circuit maintenance, a topic central to a wide variety of psychiatric and neurological conditions.