• Jun-Nan Li and Patrick L Sheets.
• Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, United States.
• Pain. 2020 Jan 1; 161 (1): 166176166-176.

AbstractDissecting the organization of circuit pathways involved in pain affect is pivotal for understanding behavior associated with noxious sensory inputs. The central nucleus of the amygdala (CeA) comprises distinct populations of inhibitory GABAergic neurons expressing a wide range of molecular markers. CeA circuits are associated with aversive learning and nociceptive responses. The CeA receives nociceptive signals directly from the parabrachial nucleus (PBn), contributing to the affective and emotional aspects of pain. Although the CeA has emerged as an important node in pain processing, key questions remain regarding the specific targeting of PBn inputs to different CeA subregions and cell types. We used a multifaceted approach involving transgenic reporter mice, viral vector-mediated optogenetics, and brain slice electrophysiology to delineate cell-type-specific functional organization of the PBn-CeA pathway. Whole-cell patch clamp recordings of molecularly defined CeA neurons while optogenetically driving long-range inputs originating from PBn revealed the direct monosynaptic excitatory inputs from PBn neurons to 3 major subdivisions of the CeA: laterocapsular (CeC), lateral (CeL), and medial (CeM). Direct monosynaptic excitatory inputs from PBn targeted both somatostatin-expressing (SOM+) and corticotropin-releasing hormone expressing (CRH+) neurons in the CeA. We find that monosynaptic PBn input is preferentially organized to molecularly specific neurons in distinct subdivisions of the CeA. The spared nerve injury model of neuropathic pain differentially altered PBn monosynaptic excitatory input to CeA neurons based on molecular identity and topographical location within the CeA. These results provide insight into the functional organization of affective pain pathways and how they are altered by chronic pain.

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