Mechanisms and functions of amygdala-hippocampus beta synchrony

PROJECT SUMMARY Using intracranial EEG (iEEG) recordings from human epilepsy patients, we previously identified a biomarker, based on beta-frequency coherence between the amygdala and hippocampus, that tracks real-time fluctuations in self-reported mood and anxiety. We recently published a study which validates that this same biomarker predicts emotional state in mice, and shows that it is specifically associated with bursts of beta- frequency synchronization between somatostatin (SST)-expressing neurons in the basolateral amygdala (BLA) and ventral hippocampus (vHPC). We further showed that patterns of optogenetic stimulation designed to disrupt or reproduce this cell type-specific pattern of synchronization bidirectionally modulate avoidance and risk-assessment behaviors in the elevated plus maze. Having successfully back-translated this human biomarker to mice, identified associated cell types, and found that it causally influences behavior, we are now poised to understand its mechanisms and functions. Here we propose to identify specific connections between the BLA and vHPC which generate this pattern of synchrony. We will then use voltage indicators, calcium indicators, and electrophysiology to study how these bursts of beta-frequency synchronization dynamically re- organize activity within the BLA-vHPC circuit in a behaviorally-dependent manner. We hypothesize that this facilitates interactions between specific cell types within the BLA-vHPC circuit in order to recruit output pathways that promote particular behaviors. Finally, we will map out the cell type-specific organization of connections within and between the BLA and vHPC. Understanding this pattern of connectivity will help elucidate microcircuit mechanisms through which specific connections generate bursts of beta-frequency synchronization, and through which BLA-vHPC cell types interact during bursts in order to perform specific information processing functions. Results from this project will be broadly useful for understanding the function of these two key nodes in the limbic system, yield insights about the general function of oscillations in brain circuits, and advance the development of strategies for therapeutic modulation targeting this cell type-specific pattern of rhythmic synchronization.