Thursday, April 25, 2024
4/25/2024
PROJECT SUMMARY Anxiety and risky behaviors are the most prevalent mental health concerns facing adolescents. The adolescent brain is characterized by a high degree of neural plasticity in which circuit-level formation is very responsive to environmental changes. There is increasing evidence that most psychiatric disorders have a developmental origin that is the result of early disturbances in this complex process. Adolescence is a period in which exposure to altered environmental lighting is decidedly common, as 50% of adolescents in the USA reported using computers, smartphones, and tablets before bedtime. This intensity of artificial light and the duration of exposure past sunset is unprecedented in human history. Despite the widespread exposure to night-time light in adolescents, our knowledge of the mechanisms by which our brain adapts to irregular environmental lighting is still incomplete. The medial amygdala (MeA) plays a key role in processing emotions and is also one of the regions, among others, that receives and processes light information. Thus, artificial changes in light exposure levels, timing, and regularity might generate confusing signals in this region, affecting neuroplasticity and emotional responses. To study whether light affects neuroplasticity in the MeA, thereby increasing vulnerability to anxiety and risk-decision making in adolescent mice, I developed a new aberrant light protocol designed to mimic human adolescent light exposure. This Pathway to Independence Award will provide the opportunity to build on my expertise in neurobiology and behavioral neuroscience while developing my abilities in fiber photometry and RNA-sequencing. Aim 1 is built upon our preliminary data showing that aberrant light exposure alters neurotransmitter plasticity in the MeA of adolescent mice, and that such neuroplasticity contributes to their vulnerability to anxiety and risky behaviors. Under the supervision of Dr. Barnes and Dr. Young, I will use the Iowa Gambling Task to test whether aberrant light exposure alters risk-taking behaviors differently in adolescent and adult mice. With additional mentorship from Dr. Ramanathan in the K99 phase, I will explore whether aberrant light affects neural activity in selected MeA neurons using fiber photometry-based calcium recording in behaving mice. In Aim 2, under the supervision of Dr. Preissl, I will investigate whether aberrant light exposure affects gene expression in MeA neurons and its target regions participating in anxiety and risky choice behaviors, such as the central amygdala and the bed nucleus of the stria terminalis. These experiments will prepare me for the R00 phase in which I will study the role of amygdala circuitry in light-mediated anxiety and risky behavior by combining pharmacological manipulation of amygdalar neurons, fiber photometry, and translational mouse models (Aim 3). Because the amygdala is a well-conserved structure, the proposed research will be translationally relevant for understanding the effect of altered environmental lighting during pubertal development and for the design of appropriate integrative interventions to promote emotional well-being in adolescents.
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