Neuroscience Graduate Program, University of California San Francisco, San Francisco, California 94143.
Department of Physiology, University of California San Francisco, San Francisco, California 94143.
J Neurosci. 2019 Sep 4;39(36):7102-7117. doi: 10.1523/JNEUROSCI.3137-18.2019. Epub 2019 Jul 18.
The lateral septum (LS) plays an important role in regulating aggression. It is well recognized that LS lesions lead to a dramatic increase in aggressive behaviors. A better understanding of LS neurophysiology and its functional output is therefore important to assess LS involvement in regulating aggression. The LS is a heterogeneous structure that maintains inputs and outputs with multiple brain regions, and is also divided into subregions that innervate one another. Thus, it is challenging to identify the exact cell type and projections for characterization. In this study, we determined the expression pattern of the calcium-activated chloride channel, TMEM16B, in the LS of both male and female mice. We then investigated the physiological contribution of the calcium-activated chloride channel to LS neuronal signaling. By performing whole-cell patch-clamp recording, we showed that TMEM16B alters neurotransmitter release at the hippocampal-LS synapse, and regulates spike frequency and spike frequency adaptation in subpopulations of LS neurons. We further demonstrated that loss of TMEM16B function promotes lengthened displays of aggressive behaviors by male mice during the resident intruder paradigm. In conclusion, our findings suggest that TMEM16B function contributes to neuronal excitability in subpopulations of LS neurons and the regulation of aggression in male mice. Aggression is a behavior that arose evolutionarily from the necessity to compete for limited resources and survival. One particular brain region involved in aggression is the lateral septum (LS). In this study, we characterized the expression of the TMEM16B calcium-activated chloride channel in the LS and showed that TMEM16B regulates the action potential firing frequency of LS neurons. We discovered that loss of TMEM16B function lengthens the displays of aggressive behaviors in male mice. These findings suggest that TMEM16B plays an important role in regulating LS neuronal excitability and behaviors associated with LS function, thereby contributing to our understanding of how the LS may regulate aggression.
外侧隔核（LS）在调节攻击行为方面起着重要作用。众所周知，LS 损伤会导致攻击行为急剧增加。因此，更好地了解 LS 的神经生理学及其功能输出对于评估 LS 在调节攻击行为中的作用非常重要。LS 是一个异构结构，它与多个脑区保持输入和输出，并且还分为相互支配的亚区。因此，确定确切的细胞类型和投射对于特征描述是具有挑战性的。在这项研究中，我们确定了 TMEM16B 钙激活氯离子通道在雄性和雌性小鼠 LS 中的表达模式。然后，我们研究了钙激活氯离子通道对 LS 神经元信号传递的生理贡献。通过进行全细胞膜片钳记录，我们表明 TMEM16B 改变了海马体-LS 突触处的神经递质释放，并调节了 LS 神经元亚群中的尖峰频率和尖峰频率适应。我们进一步证明，TMEM16B 功能的丧失会促进雄性小鼠在常驻入侵者范式中表现出更长时间的攻击行为。总之，我们的研究结果表明，TMEM16B 功能有助于 LS 神经元亚群的神经元兴奋性和雄性小鼠的攻击性调节。攻击性是一种从竞争有限资源和生存的必要性中演化而来的行为。参与攻击行为的一个特定脑区是外侧隔核（LS）。在这项研究中，我们对 TMEM16B 钙激活氯离子通道在 LS 中的表达进行了表征，并表明 TMEM16B 调节 LS 神经元动作电位的发放频率。我们发现 TMEM16B 功能的丧失会延长雄性小鼠攻击行为的表现。这些发现表明 TMEM16B 在调节 LS 神经元兴奋性和与 LS 功能相关的行为方面起着重要作用，从而有助于我们理解 LS 如何调节攻击性。
