Neural Circuits for Context-Dependent Control of Vocal Communication

PROJECT SUMMARY/ABSTRACT Vocal communication is essential for human social relationships, and deficits in vocal communication that characterize autism spectrum disorder (ASD) have devastating impacts on the affected individuals and on society. Despite the importance of vocalization to social behavior, the brain circuits that allow animals to vocalize appropriately according to behavioral context remain poorly understood. This proposal seeks to apply powerful intersectional tools in the mouse to (1) identify and characterize forebrain-to-midbrain circuits that underlie the context-dependent control of social vocalizations and (2) to understand the midbrain circuits that underlie the production of distinct acoustic categories of vocalization. Prior work has shown that midbrain- projecting neurons of the preoptic hypothalamus regulate courtship vocalizations in male mice. Aside from these neurons, the forebrain inputs to the midbrain that regulate social vocalizations, and whether the relevant inputs differ according to social context, remains unknown. Aim 1 will combine in vivo calcium imaging, neuronal silencing, and mapping of axonal projections to test the hypothesis that midbrain-projecting preoptic neurons regulate social vocalizations produced during affiliative female-female interactions. In Aim 2, retrograde tracing from the midbrain will be combined with Fos mapping and light sheet imaging of optically cleared brains to identify novel populations of midbrain-projecting forebrain neurons that are active during and may regulate vocal communication during courtship, during female-female interactions, or in both contexts. In Aim 3, activity-dependent labeling in the midbrain will be combined with neuronal ablation and retrograde tracing from hindbrain vocal premotor neurons to test the hypothesis that distinct sets of midbrain neurons control the production of different acoustic categories of vocalization. This work will delineate brain circuits that underlie the context-dependent control of vocalization in the mammalian brain, and more broadly, that link the encoding of social information to the flexible and appropriate execution of social behaviors. By identifying core mechanisms of healthy vocal communication, this work will provide a foundation to understand neural circuit alterations the contribute to vocal communication differences in mouse models of ASD and other neurodevelopmental disorders.