Neural Systems Laboratory, Department of Health Sciences, Boston University, Boston, Massachusetts 022152.
Graduate Program in Neuroscience, Boston University and School of Medicine, Boston, Massachusetts 02118.
J Neurosci. 2023 Apr 26;43(17):3061-3080. doi: 10.1523/JNEUROSCI.2066-22.2023. Epub 2023 Mar 28.
The amygdala, hippocampus, and subgenual cortex area 25 (A25) are engaged in complex cognitive-emotional processes. Yet pathway interactions from hippocampus and A25 with postsynaptic sites in amygdala remain largely unknown. In rhesus monkeys of both sexes, we studied with neural tracers how pathways from A25 and hippocampus interface with excitatory and inhibitory microcircuits in amygdala at multiple scales. We found that both hippocampus and A25 innervate distinct as well as overlapping sites of the basolateral (BL) amygdalar nucleus. Unique hippocampal pathways heavily innervated the intrinsic paralaminar basolateral nucleus, which is associated with plasticity. In contrast, orbital A25 preferentially innervated another intrinsic network, the intercalated masses, an inhibitory reticulum that gates amygdalar autonomic output and inhibits fear-related behaviors. Finally, using high-resolution confocal and electron microscopy (EM), we found that among inhibitory postsynaptic targets in BL, both hippocampal and A25 pathways preferentially formed synapses with calretinin (CR) neurons, which are known for disinhibition and may enhance excitatory drive in the amygdala. Among other inhibitory postsynaptic sites, A25 pathways innervated the powerful parvalbumin (PV) neurons which may flexibly regulate the gain of neuronal assemblies in the BL that affect the internal state. In contrast, hippocampal pathways innervated calbindin (CB) inhibitory neurons, which modulate specific excitatory inputs for processing context and learning correct associations. Common and unique patterns of innervation in amygdala by hippocampus and A25 have implications for how complex cognitive and emotional processes may be selectively disrupted in psychiatric disorders. The hippocampus, subgenual A25, and amygdala are associated with learning, memory, and emotions. We found that A25 is poised to affect diverse amygdalar processes, from emotional expression to fear learning by innervating the basal complex and the intrinsic intercalated masses. Hippocampal pathways uniquely interacted with another intrinsic amygdalar nucleus which is associated with plasticity, suggesting flexible processing of signals in context for learning. In the basolateral (BL) amygdala, which has a role in fear learning, both hippocampal and A25 interacted preferentially with disinhibitory neurons, suggesting a boost in excitation. The two pathways diverged in innervating other classes of inhibitory neurons, suggesting circuit specificities that could become perturbed in psychiatric diseases.
杏仁核、海马体和 subgenual 皮质区 25（A25）参与复杂的认知-情绪过程。然而，海马体和 A25 与杏仁核后突触位点的通路相互作用在很大程度上仍不清楚。在两性恒河猴中，我们使用神经示踪剂研究了 A25 和海马体的通路如何在多个尺度上与杏仁核的兴奋性和抑制性微电路接口。我们发现，海马体和 A25 都支配着杏仁核基底外侧（BL）核的不同和重叠部位。独特的海马体通路强烈支配着与可塑性相关的固有旁侧 BL 核。相比之下，眶额 A25 优先支配着另一个内在网络，即中间隔网络，这是一个抑制性网状结构，控制着杏仁核的自主输出，并抑制与恐惧相关的行为。最后，使用高分辨率共聚焦和电子显微镜（EM），我们发现，在 BL 中的抑制性突触后靶点中，海马体和 A25 通路都优先与 calretinin（CR）神经元形成突触，这些神经元以去抑制作用而闻名，可能增强杏仁核的兴奋性驱动。在其他抑制性突触后部位中，A25 通路支配着强大的 parvalbumin（PV）神经元，这些神经元可以灵活地调节 BL 中神经元集合的增益，从而影响内部状态。相比之下，海马体通路支配着 calbindin（CB）抑制性神经元，这些神经元调节特定的兴奋性输入，用于处理上下文和学习正确的关联。海马体和 A25 在杏仁核中的共同和独特的支配模式对复杂的认知和情绪过程如何在精神障碍中被选择性地破坏具有启示意义。海马体、亚区 A25 和杏仁核与学习、记忆和情绪有关。我们发现，A25 通过支配基底复合体和内在的中间隔网络，能够影响杏仁核的多种过程，从情绪表达到恐惧学习。海马体通路与另一个与可塑性相关的内在杏仁核核团独特地相互作用，这表明在上下文环境中对信号进行灵活处理以进行学习。在参与恐惧学习的基底外侧（BL）杏仁核中，海马体和 A25 都与去抑制神经元优先相互作用，这表明兴奋得到了增强。这两个通路在支配其他类别的抑制性神经元方面存在分歧，这表明存在特定于回路的特异性，这可能在精神疾病中受到干扰。
