Survival in a hostile environment requires the ability to assess potential threats and take the most appropriate
defensive action. Accumulating evidence suggests that the amygdala is well positioned to integrate information
about threats and to guide or shift responses along a spectrum of potential defensive behaviors. In both
humans and mice, the amygdala plays an essential role in defensive responses to the threat of suffocation,
signaled by rising systemic carbon dioxide (CO2) levels in the body. Lesioning the amygdala, or manipulating it
more precisely in other ways, reduces some defensive behaviors evoked by CO2 inhalation (e.g. freezing)
while simultaneously increasing others (e.g. fight-or-flight). Because CO2 inhalation evokes a variety of
defensive responses in a robust, reproducible, and concentration-dependent manner, CO2 provides a
straightforward and translatable approach to studying the amygdala's role in defensive behavior regulation. In
this application, we propose to study defensive behaviors evoked by CO2 using state-of-the-art, neuron-
specific manipulations and electrophysiological recording to deconstruct roles of select neuron populations in
the basolateral amygdala (BLA). We hypothesize that distinct defensive behaviors are differentially regulated
by the BLA and that principal neurons and interneurons in the BLA each play unique roles. To test this
hypothesis we will use genetic, optogenetic, and electrophysiological approaches to specifically activate and
silence specific BLA neuron populations and quantify the effects on neural activity and defensive behaviors.
Together these experiments will allow us to discern how these neurons regulate different defensive behaviors.
Understanding basic mechanisms that guide or shift defensive behaviors along their spectrum will be essential
for identifying abnormalities in these processes and for finding ways to correct them. This knowledge will
ultimately impact mental illnesses where defensive behaviors are inappropriately extreme such as panic
disorder and post-traumatic stress disorder.