Garrett Stanley, faculty host
Title: Investigating social spaces: Role of the prefrontal cortex in mediating social investigation
Malavika Murugan, PhD
Department of Biology
Although social interactions are crucial for the survival and well-being of all mammals, little is known about the neural substrates that support such behaviors. Several lines of evidence implicate the medial prefrontal cortex (mPFC) as important to mediating social behaviors. Combining cellular resolution imaging and optogenetics, we had earlier showed that mPFC neurons that project to the nucleus accumbens (NAc) encode a conjunction of social and spatial information and use this information to form social-spatial associations (Murugan et al., Cell, December 2017). However, in addition to the NAc, the mPFC projects to a number of downstream regions and it remains unclear if other mPFC projections play distinct (if any) role in regulating social behavior. In this study, we compared the role of two anatomical subpopulations in the mPFC: mPFC-NAc and mPFC-VTA (ventral tegmental area) neurons in mediating social behaviors. Using monosynaptic rabies tracing technology, we first established that the two subpopulations have significantly different patterns of inputs. The largest fraction of inputs to the mPFC-NAc neurons arose from the hippocampal formation. In contrast, mPFC-VTA neurons received majority of their input from thalamic structures. Additionally, we found that mPFC-NAc neurons received more inputs from the olfactory sensory areas such as piriform cortex and the taenia tecta relative to mPFC-VTA neurons, while the mPFC-VTA neurons received more input from the motor cortex. These significant anatomical differences in long range inputs suggest that these two populations likely serve different functions. To test this hypothesis and to characterize the neural dynamics of the two populations during social interactions we used cellular resolution imaging to monitor the activity of these neurons in freely moving mice in a modified version of the three-chamber social assay. We compared the activity of mPFC-VTA neurons (n=416 neurons, 14 animals) during social behaviors to that previously observed in the mPFC-NAc neurons (n=987 neurons, 8 animals). Interestingly, we found that significantly fewer mPFC-VTA neurons had social responses that depended on the spatial location of the social target compared to the mPFC-NAc population. We also found that, a significantly larger fraction of mPFC-VTA neurons encoded relative distance to the social target compared to the mPFC-NAc neurons. Taken together these results suggest that these two anatomical subpopulations of mPFC neurons play roles in mediating social behaviors.