PMID- 36623874 OWN - NLM STAT- MEDLINE DCOM- 20230222 LR - 20240214 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 43 IP - 7 DP - 2023 Feb 15 TI - Arc-Expressing Accessory Olfactory Bulb Interneurons Support Chemosensory Social Behavioral Plasticity. PG - 1178-1190 LID - 10.1523/JNEUROSCI.0847-22.2022 [doi] AB - The accessory olfactory system (AOS) is critical for the development and expression of social behavior. 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, we sought to better understand how Arc-expressing IGCs shape AOB information processing and social behavior in the context of territorial aggression. We used "ArcTRAP" (Arc-CreERT2) transgenic mice to selectively and permanently label Arc-expressing IGCs following male-male resident-intruder interactions. Using whole-cell patch-clamp electrophysiology, we found that Arc-expressing IGCs display increased intrinsic excitability for several days after a single resident-intruder interaction. Further, we found that Arc-expressing IGCs maintain this increased excitability across repeated resident-intruder interactions, during which resident mice increase or "ramp" their aggression. We tested the hypothesis that Arc-expressing IGCs participate in ramping aggression. Using a combination of ArcTRAP mice and chemogenetics (Cre-dependent hM4D(G(i))-mCherry AAV injections), we found that disruption of Arc-expressing IGC activity during repeated resident-intruder interactions abolishes the ramping aggression exhibited by resident male mice. This work shows that Arc-expressing AOB IGC ensembles are activated by specific chemosensory environments, and play 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.SIGNIFICANCE STATEMENT The accessory olfactory system plays a vital role in rodent chemosensory social behavior. We studied experience-dependent plasticity in the accessory olfactory bulb and found that internal granule cells expressing the immediate-early gene Arc after the resident-intruder paradigm increase their excitability for several days. We investigated the roles of these Arc-expressing internal granule cells on chemosensory social behavior by chemogenetically manipulating their excitability during repeated social interactions. We found that inhibiting these cells eliminated intermale aggressive ramping 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. CI - Copyright (c) 2023 Zuk et al. FAU - Zuk, Kelsey E AU - Zuk KE AD - Neuroscience Graduate Program, University of Texas Southwestern Medical Center, Dallas, Texas 75390. AD - Department of Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642. FAU - Cansler, Hillary L AU - Cansler HL AUID- ORCID: 0000-0001-8267-0515 AD - Department of Pharmacology, University of Florida College of Medicine, Gainesville, Florida 32603. FAU - Wang, Jinxin AU - Wang J AD - Department of Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642. FAU - Meeks, Julian P AU - Meeks JP AUID- ORCID: 0000-0002-7537-4491 AD - Department of Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642 julian_meeks@urmc.rochester.edu. AD - Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642. LA - eng GR - F31 DC018440/DC/NIDCD NIH HHS/United States GR - R01 DC015784/DC/NIDCD NIH HHS/United States GR - R01 DC017985/DC/NIDCD NIH HHS/United States GR - R21 NS104826/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20230109 PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 SB - IM MH - Mice MH - Male MH - Female MH - Animals MH - *Olfactory Bulb/physiology MH - *Interneurons/physiology MH - Neurons MH - Social Behavior MH - Aggression MH - Mice, Transgenic MH - Mammals PMC - PMC9962775 OTO - NOTNLM OT - Arc OT - accessory olfactory bulb OT - aggression OT - interneuron OT - plasticity OT - social behavior EDAT- 2023/01/10 06:00 MHDA- 2023/02/22 06:00 PMCR- 2023/02/15 CRDT- 2023/01/09 20:52 PHST- 2022/05/02 00:00 [received] PHST- 2022/11/18 00:00 [revised] PHST- 2022/11/22 00:00 [accepted] PHST- 2023/01/10 06:00 [pubmed] PHST- 2023/02/22 06:00 [medline] PHST- 2023/01/09 20:52 [entrez] PHST- 2023/02/15 00:00 [pmc-release] AID - JNEUROSCI.0847-22.2022 [pii] AID - JN-RM-0847-22 [pii] AID - 10.1523/JNEUROSCI.0847-22.2022 [doi] PST - ppublish SO - J Neurosci. 2023 Feb 15;43(7):1178-1190. doi: 10.1523/JNEUROSCI.0847-22.2022. Epub 2023 Jan 9.