Grant: Discovery Grants Program - Individual

The medial prefrontal cortex (mPFC) plays important roles in memory, decision making, and social behaviour. The mPFC projects directly to subcortical structures that generate ultrasonic vocalizations, both the 50 kHz calls associated with positive affect and the 22 kHz calls associated with negative affect. However, much remains unknown about how ultrasonic vocalizations are used and what role the mPFC plays in regulating them. My first aim is to learn more about how vocalizations are used in social interactions. The 50 kHz calls can be subdivided into as many as 14 distinct call types and we have recently shown that many of these calls have specific behavioural correlates. These studies have been limited by the inability to determine which of two interacting animals is giving a particular call. Hence, I propose to record vocalizations while simultaneously recording larynx muscle electromyographic (EMG) signals using an implanted wireless transmitter. This technique will be applied to playful interactions in juvenile rats, potentially aggressive encounters among adult rats, and mating in male/female pairs. This will provide a much clearer picture of exactly how vocalizations are used to coordinate social interactions. My second aim is to determine which parts of mPFC are most directly involved in vocal communication. Mapping studies in monkeys have identified a region in the cingulate cortex where vocalizations can be elicited by electrical stimulation. Do rats have a similar region? To answer this question, I propose to use electrode arrays to map the cingulate vocalization region in rats. A second experiment using focal lesions will test the causal role of mPFC subregions in vocalizations. Together, these studies will clarify exactly which mPFC regions are most critical in regulating vocal communication. A third and final aim is to examine the encoding of ultrasonic vocalizations in ensembles of mPFC cells. Specifically, rats will be implanted with microdrives with multiple electrodes, allowing for the simultaneous recording of 50-100 cells in mPFC in behaving rats. A first study will examine the responses of single cells to the playback of recorded calls (22 kHz and the various types of 50 kHz calls). A second experiment will examine neural responses during the production of vocalizations. These experiments will address question such as: 1) What fraction of mPFC cells are responsive to vocalizations? 2) Are different cells tuned to different calls? and 3) Are 22 kHz and 50 kHz cells intermingled or segregated? In sum, the proposed research with provide a much more detailed picture of how ultrasonic vocalizations are used to coordinate social interactions, elucidate which regions of mPFC are involved in vocal regulation, and provide insights into how the mPFC represents vocalizations. Its primary impact will be to open an entirely new avenue of research into how mPFC regulates social communication.