Arc-Expressing Accessory Olfactory Bulb Interneurons Support Chemosensory Social Behavioral Plasticity.
Arc-Expressing Accessory Olfactory Bulb Interneurons Support Chemosensory Social Behavioral Plasticity.
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DOI：
10.1523/jneurosci.0847-22.2022
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发表时间：
2023-02-15
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辅助嗅觉系统(AOS)对社会行为的发展和表达起着至关重要的作用。AOS中的第一个专用回路是辅助嗅球(AOB)，在经过社会经验后，它在雄性和雌性小鼠身上显示出细胞和网络的可塑性。在AOB中，称为内颗粒细胞(IGCs)的中间神经元在雄性间攻击或交配后表达可塑性相关的即刻早期基因Arc。在这里，我们试图更好地理解在领土侵略的背景下，表达Arc的IGCs如何塑造AOB信息处理和社会行为。我们使用“ArcTRAP”(Arc-CreERT2)转基因小鼠来选择性和永久性地标记雄性-雄性居民-入侵者相互作用后表达Arc的IGCs。利用全细胞膜片钳电生理学，我们发现表达Arc的IGCs在单个居住者-入侵者相互作用后的几天内表现出更强的内在兴奋性。此外，我们发现，表达Arc的IGCs在反复的居民-入侵者相互作用中保持这种增强的兴奋性，在此期间，驻留小鼠增加或“增强”它们的攻击性。我们检验了Arc表达的IGCs参与斜坡式攻击性的假设。使用ArcTRAP小鼠和化学遗传学(Cre依赖的hM4D(GI)-mCherry AAV注射)的组合，我们发现在反复的常驻-入侵者互动过程中中断Arc表达的IGC活性可以消除常驻雄性小鼠表现出的猛烈攻击行为。本工作表明，表达Arc的AOB IGC系综被特定的化学感觉环境激活，并在性典型社会行为的建立和表达中发挥不可或缺的作用。这些研究确定了早期化学感觉回路中的一组可塑性中间神经元，这些中间神经元表现出与简单记忆形成一致的生理特征，增加了我们对中枢化学感觉加工和哺乳动物社会行为的理解。意义陈述副嗅觉系统在啮齿动物的化学感觉社会行为中起着至关重要的作用。我们研究了副嗅球的经验依赖性可塑性，发现在常驻-入侵者范式之后，表达即刻早期基因Arc的内部颗粒细胞在几天内增加了它们的兴奋性。我们研究了这些表达Arc的内部颗粒细胞在化学感觉社会行为中的作用，方法是在重复的社会互动中通过化学遗传学控制它们的兴奋性。我们发现，抑制这些细胞可以消除雄性间的攻击性斜行行为。这些研究确定了早期化学感觉回路中的一组可塑性中间神经元，这些中间神经元表现出与简单记忆形成一致的生理特征，增加了我们对中枢化学感觉加工和哺乳动物社会行为的理解。
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(Gi)-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.
影响因子：
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作者：
Walther G;Zimmerman N;Moore W;Parks D;Meehan S;Belitskaya I;Pan J;Herzenberg L
通讯作者：
Herzenberg L
影响因子：
3
作者：
Grinevich, Valery;Kolleker, Alexander;Eliava, Marina;Takada, Naoki;Takuma, Hiroshi;Fukazawa, Yugo;Shigemoto, Ryuichi;Kuhl, Dietmar;Waters, Jack;Seeburg, Peter H.;Osten, Pavel
通讯作者：
Osten, Pavel