State-dependent encoding of exploratory behaviour in the amygdala.

The behaviour of an animal is determined by metabolic, emotional and social factors1,2. Depending on its state, an animal will focus on avoiding threats, foraging for food or on social interactions, and will display the appropriate behavioural repertoire3. Moreover, survival and reproduction depend on the ability of an animal to adapt to changes in the environment by prioritizing the appropriate state4. Although these states are thought to be associated with particular functional configurations of large-brain systems5,6, the underlying principles are poorly understood. Here we use deep-brain calcium imaging of mice engaged in spatial or social exploration to investigate how these processes are represented at the neuronal population level in the basolateral amygdala, which is a region of the brain that integrates emotional, social and metabolic information. We demonstrate that the basolateral amygdala encodes engagement in exploratory behaviour by means of two large, functionally anticorrelated ensembles that exhibit slow dynamics. We found that spatial and social exploration were encoded by orthogonal pairs of ensembles with stable and hierarchical allocation of neurons according to the saliency of the stimulus. These findings reveal that the basolateral amygdala acts as a low-dimensional, but context-dependent, hierarchical classifier that encodes state-dependent behavioural repertoires. This computational function may have a fundamental role in the regulation of internal states in health and disease.

Adaptive disinhibitory gating by VIP interneurons permits associative learning.

Learning drives behavioral adaptations necessary for survival. While plasticity of excitatory projection neurons during associative learning has been extensively studied, little is known about the contributions of local interneurons. Using fear conditioning as a model for associative learning, we found that behaviorally relevant, salient stimuli cause learning by tapping into a local microcircuit consisting of precisely connected subtypes of inhibitory interneurons. By employing deep-brain calcium imaging and optogenetics, we demonstrate that vasoactive intestinal peptide (VIP)-expressing interneurons in the basolateral amygdala are activated by aversive events and provide a mandatory disinhibitory signal for associative learning. Notably, VIP interneuron responses during learning are strongly modulated by expectations. Our findings indicate that VIP interneurons are a central component of a dynamic circuit motif that mediates adaptive disinhibitory gating to specifically learn about unexpected, salient events, thereby ensuring appropriate behavioral adaptations.

Amygdala ensembles encode behavioral states.

Internal states, including affective or homeostatic states, are important behavioral motivators. The amygdala regulates motivated behaviors, yet how distinct states are represented in amygdala circuits is unknown. By longitudinally imaging neural calcium dynamics in freely moving mice across different environments, we identified opponent changes in activity levels of two major, nonoverlapping populations of basal amygdala principal neurons. This population signature does not report global anxiety but predicts switches between exploratory and nonexploratory, defensive states. Moreover, the amygdala separately processes external stimuli and internal states and broadcasts state information via several output pathways to larger brain networks. Our findings extend the concept of thalamocortical "brain-state" coding to include affective and exploratory states and provide an entry point into the state dependency of brain function and behavior in defined circuits.