Neurobiological responses of somatostatin neuronal circuits to environmental light disruptions during pubertal development - Over 80% of the world's population lives under light-polluted skies, with indoor light exposure rising due to factors like electronic devices. Exposure to altered light environments induces circadian disruptions, leading to adverse neurophysiological and behavioral changes including anxiety disorders. Adolescents, who often have altered sleep patterns and extensive electronic device use, are particularly vulnerable to circadian disruptions. However, the neurobiological effects of light interventions on brain circuits and behaviors during pubertal development are understudied. Mammalian light perception involves specialized retinal cells that communicate light information to various brain regions, including the medial amygdala (MeA), which processes environmental cues to control emotional responses. Our long-term goal is to understand how the MeA circuit adapts to light environments during adolescence, and whether light interventions can enhance resilience and prevent anxiety disorders induced by circadian disruptions. We recently demonstrated that altered light environments during adolescence increased avoidance behaviors, increased somatostatin neuronal activity and decreased inward-rectifying potassium channels expression in the MeA. MeA neurons in turn project to the bed nucleus of the stria terminalis (BNST), a brain region involved in avoidance responses. Given the key role of somatostatin signaling in the amygdala in regulating affective behaviors, we seek to characterize the mechanism by which somatostatin neurons in the MeA adapt to light environments to regulate emotional responses and promote resilience. We will test the general hypothesis that somatostatin neurons in the MeA act as a key regulator, capable of adjusting to light environments to influence adaptive responses (resilience). Three Specific Aims are proposed to functionally dissect the role of somatostatin neurons in mediating lightinduced adaptive behaviors: In Aim 1, we will investigate whether somatostatin neurons in the MeA are required for light-induced avoidance behavior through chemogenetic manipulations and cell-type-specific ablation of somatostatin expression in adolescent mice exposed to chronic light cycles disruption. In Aim 2, we will establish the role of inward-rectifying potassium channel in regulating light-induced increase of somatostatin neuronal activity in the MeA regulating avoidance behaviors. In Aim 3, we will study MeA somatostatin cells downstream projections to uncover the circuits mediating light-induced avoidance behaviors by employing in vivo fiber photometry for neuronal activity and somatostatin release recording in the BNST of adolescent mice exposed to chronic light cycle disruption. We will also use optogenetic approach to inhibit MeA somatostatin synapsis terminals into the BNST while testing adolescent mice for light-induced avoidance behaviors. By integrating a diverse set of cutting-edge methodologies, this project will advance our understanding of the adaptive mechanisms of the MeA somatostatin circuit in response to light environments. Our goal is to provide pre-clinical data to develop safe light interventions that enhance resilience and prevent affective disorders in adolescents experiencing circadian disruptions.
