The brainstem vocal control circuits

Abstract Vocalization is used in many species for social and emotional communications. Interestingly, mice can emit two types of vocalizations: ultrasonic vocalizations during social and courtship interactions (USVs) and audible squeaks in response to stress and pain. While previous studies, including our owns, have uncovered higher centers regulating vocalization, such as the gating of USV production by neurons in the periaqueductal gray (PAG), the precise neuronal cell types and the mechanisms for producing the actual sounds via vocal cord adduction and vocal-breathing coordination remain poorly understood. The circuit elements that selectively required for eliciting audible squeaks in mice also remain unknown. The objective of this research proposal is to solve these two fundamental questions of vocal control. In preliminary studies, we have used activity-dependent method that identified excitatory vocal premotor neurons located in the retroambiguus nucleus (RAmVOC) as sufficient for driving vocal-cord closure and elicit USVs. RAmVOC neurons are also absolutely necessary for both USVs and squeaks Here, we will (1) transcriptomically define the cell types of all laryngeal premotor (pre-MNlary) and as well as all RAmVOC presynaptic (pre- RAmVOC) neurons; (2) determine the activity and function of preBotCInh – RAmVOC pathways in vocal- respiratory coupling; and (3) determine the roles of different populations of periaqueductal gray (PAG), Kölliker-Fuse (KF), nucleus solitary tract (NTS) neurons in driving audible emotional vocalizations. We expect to not only identify the hitherto unknown circuits that trigger emotional cries but also reveal precise cells and mechanisms underlying vocal-respiration coordination and lay molecular foundations for future dissection of other aspects of vocal control (pitch and shape of syllables), for finding potential treatment targets for dysphonia and other disorders related to motor speech productions, as well as for revealing how other physiological needs control vocal cord movements in health and diseases.