THE ROLE OF VENTROMEDIAL PREFRONTAL PARVALBUMIN NEURONS IN MEDIATING PROACTIVE DEFENSIVE RESPONSES

Abstract

When under an approaching threat, it is vital that an animal is able to initiate a new action, which often requires the termination of an ongoing action. Failure to implement a proper defensive action at the correct time can significantly reduce an animal’s survival chance. The ventromedial prefrontal cortex (vmPFC) has been known to play a crucial role in suppressing passive reactive freezing responses and promoting active defensive actions. In this dissertation, we interrogated the role of parvalbumin neurons (PV) within the mouse vmPFC in supporting the implementation of proactive defensive action. We first used fiber photometry to record vmPFC PV neurons in an active avoidance task and found that vmPFC PV neuronal activity increased as animals transitioned from a freezing to active state to avoid the upcoming shock after hearing the shock-predicting tone. Importantly, vmPFC PV neuronal activity was not modulated by non-defensive movements such as voluntary movement or approaching a known reward. While suppression of this population does not affect voluntary movement or reward approaches, it does extend the freezing duration and delayed the avoidance response to a shock-predicting tone. These results suggest that vmPFC PV neuronal activity signals are necessary for initiating active avoidance, a type of proactive defensive action. To further confirm the importance of vmPFC PV neurons in regulating proactive defensive actions, we recorded vmPFC PV neuronal activity through fiber photometry when mice explored and assessed the risk in a novel and exposed environment. We first showed the neuronal activity increased as mice reared (stood on their hind limbs and stretched their body to look up) in an open field test (OFT). Then through using an elevated plus maze, we found that vmPFC PV neuronal activity at the closed arm exit differed based on the mouse’s future actions. The vmPFC PV neuronal activity was only elevated in the trials where mice eventually turned into an exposed and risky open arm. In trials where mice eventually chose the safer option by going into another closed arm or retracting back to the original closed arm, vmPFC PV neuronal activity remained unchanged or even decreased. These results show that the activity of vmPFC PV neurons also signals the initiation of proactive risk assessing behaviors when no distinct threat is present. Together, these results demonstrate the importance of vmPFC PV neurons in supporting the initiation of proactive defensive responses that are crucial for an animal’s survival.