The emergence of genetic tools has provided new means of mapping functionality in central amygdala (CeA) neuron populations based on their molecular profiles, response properties, and importantly, connectivity patterns. While abundant evidence indicates that neuronal signals arrive in the CeA eliciting both aversive and appetitive behaviors, our understanding of the anatomy of the underlying long-range CeA network remains fragmentary. In this study, we combine viral tracings, electrophysiological, and optogenetic approaches to establish in male mice, a wiring chart between the insula cortex (IC), a major sensory input region of the lateral and capsular part of the CeA (CeL/C), and four principal output streams of this nucleus. We found that retrogradely labeled output neurons occupy discrete and likely strategic locations in the CeL/C, and that they are disproportionally controlled by the IC. We identified a direct line of connection between the IC and the lateral hypothalamus (LH), which engages numerous LH-projecting CeL/C cells whose activity can be strongly upregulated on firing of IC neurons. In comparison, CeL/C neurons projecting to the bed nucleus of the stria terminalis (BNST) are also frequently contacted by incoming IC axons, but the strength of this connection is weak. Our results provide a link between long-range inputs and outputs of the CeA and pave the way to a better understanding of how internal, external, and experience dependent information may impinge on action selection by the CeA.

SIGNIFICANCE STATEMENT Our current knowledge of the circuit organization within the central amygdala (CeA), a critical regulator of emotional states, includes independent information about its long-range efferents and afferents. We do not know how incoming sensory information is appraised and routed through the CeA to the different output channels. We address this issue by using three different techniques to investigate how a sensory region, the insula cortex (IC), connects with the motor, physiological and autonomic output centers of the CeA. We uncover a strong connection between the IC and the lateral hypothalamus (LH) with a monosynaptic relay in the CeA and shed new light on the previously described functions of IC and CeA through direct projections to the LH.

遗传工具的出现提供了新的映射中枢杏仁核（CeA）神经元种群功能的新方法，这些分子的分子特征，响应特性以及重要的是连通性模式。虽然大量证据表明神经元信号进入CeA引起厌恶和食欲行为，但我们对潜在的远程CeA网络的解剖结构的理解仍然是零碎的。在这项研究中，我们结合病毒示踪，电生理学和光遗传学方法在雄性小鼠中建立岛状皮层（IC），CeA的外侧和囊状部分的主要感觉输入区域（CeL / C）之间的接线图，以及该核的四个主要输出流。我们发现，逆向标记的输出神经元在CeL / C中占据离散且可能的战略位置，并且它们不受集成电路的控制。我们确定了IC与外侧下丘脑（LH）之间的直接连接线，该直线参与了许多LH投射的CeL / C细胞，这些细胞的活性在激发IC神经元时会强烈上调。相比之下，突入纹状体床核（BNST）的CeL / C神经元也经常与传入的IC轴突接触，但这种连接的强度较弱。我们的结果提供了CeA的远程输入和输出之间的链接，并为更好地了解内部，外部和经验相关信息如何影响CeA的行动铺平了道路。它参与了许多投射LH的CeL / C细胞，这些细胞的活性在发射IC神经元时会强烈上调。相比之下，突入纹状体床核（BNST）的CeL / C神经元也经常与传入的IC轴突接触，但这种连接的强度较弱。我们的结果提供了CeA的远程输入和输出之间的链接，并为更好地了解内部，外部和经验相关信息如何影响CeA的行动铺平了道路。它参与了许多投射LH的CeL / C细胞，这些细胞的活性在发射IC神经元时会强烈上调。相比之下，突入纹状体床核（BNST）的CeL / C神经元也经常与传入的IC轴突接触，但这种连接的强度较弱。我们的结果提供了CeA的远程输入和输出之间的链接，并为更好地了解内部，外部和经验相关信息如何影响CeA的行动铺平了道路。

意义陈述我们目前对中央杏仁核（CeA）内的电路组织的了解，CeA是情绪状态的关键调节器，包括有关其远程传出和传出的独立信息。我们不知道如何评估传入的感官信息并将其通过CeA路由到不同的输出通道。我们通过使用三种不同的技术来研究感觉区域，即大脑皮层（IC）如何与CeA的运动，生理和自主输出中心连接，从而解决了这一问题。我们发现在CeA中的单突触中继与IC和外侧下丘脑（LH）之间的牢固连接，并通过直接投影到LH揭示了先前描述的IC和CeA的功能。