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.
