Investigation of Accessory Olfactory Interneuron Physiology and Function After Experience-Dependent Plasticity

The accessory olfactory system (AOS) is critical for the development and expression of social behavior. Through the detection of non-volatile chemosignals, the AOS has been specifically implicated in the display of sex-typical behavior, such as mating, maternal behavior, and territorial aggression. The proper display of these sex-typical behaviors is essential for rodents to successfully navigate through their environments. The first dedicated circuit in the AOS, the accessory olfactory bulb (AOB), exhibits cellular and network plasticity in male and female mice after social experience. In the AOB, interneurons called internal granule cells (IGCs) express the plasticity-associated immediate-early gene Arc following intermale aggression or mating. Here, I sought to understand how Arc-expressing IGCs shape AOB information processing and social behavior in the context of territorial aggression over multiple days. I used "ArcTRAP" (Arc-CreERT2) transgenic mice to selectively and permanently label Arc-expressing IGCs following intermale resident-intruder interactions. Using whole-cell patch clamp electrophysiology, I found that Arc-expressing IGCs display increased intrinsic excitability for several days after a single resident-intruder interaction. Further, I found that Arc-expressing IGCs maintain this increased excitability across repeated resident-intruder interactions, during which resident mice increase or "ramp" their aggression. I tested the hypothesis that Arc-expressing IGCs participate in ramping aggression. Using a combination of ArcTRAP mice and chemogenetics (Cre-dependent hM4D(Gi)-mCherry AAV injections), I found that disrupting Arc-expressing IGC activity during repeated resident-intruder interactions abolished the ramping aggression exhibited by resident male mice. This work shows that Arc-expressing AOB IGC ensembles are activated by specific chemosensory environments, and that regulation of their activity plays an integral role in the establishment and expression of sex-typical social behavior. These studies identify a population of plastic interneurons in an early chemosensory circuit that display physiological features consistent with simple memory formation, increasing our understanding of central chemosensory processing and mammalian social behavior.