Cholinergic Contribution to Circuits Underlying DepressionAcetylcholine facilitates stress-related learning and hypervigilance and promotes stress-related avoidance mediated through actions in the amygdala and hippocampus, decreases energy demands via the hypothalamus, and increases attention to emotionally-relevant stimuli through PFC. The effects in each of these brain areas are distinct and mediated through different receptor subtypes, but can be bound into an ensemble of stress-related behaviors by release of ACh. We have therefore hypothesized that increasing ACh signaling beyond an optimal range facilitates the transition to this stress-related behavioral ensemble and consequently, blocking cholinergic receptors of different kinds may promote an adaptive, antidepressant response. In particular, we are interested in the effects of ACh in amygdala and hippocampus because both structures receive dense input from cholinergic neurons of the basal forebrain and are reciprocally connected through direct neuronal projections. We hypothesize that cholinergic neurons in the basal forebrain complex that project to these brain regions coordinate an ensemble of behaviors related to anxiety and depression. Projects on this topic include identifying cholinergic mechanisms in amygdala underlying resilience to stress-related behaviors, determining whether phasic increases in ACh signaling in hippocampus induces behaviors related to depression, identifying the neuronal subtypes and mechanisms involved in behavioral effects of aberrant ACh signaling, and determining whether distinct populations of ACh neurons projecting to amygdala and hippocampus are responsible for the effects of cholinergic signaling on stress-induced behaviors.