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Local and distal origins of limbic-related projections to the paraventricular nucleus of the hypothalamus Anonuevo, Adam Manuel Smith

Abstract

Cortico-limbic circuits are often activated in response to emotional stress to provide salient information about individual stimuli. This allows organisms to recruit adequate response mechanisms, one of which is the hypothalamic-pituitary-adrenal axis. Cellular groups directly adjacent to the paraventricular nucleus of the hypothalamus (PVN) are in position to integrate and relay cortico-limbic projections to the PVN directly. Using a neuroanatomical approach we discovered unique patterns and strengths of cortico-limbic projections to separate cell groups in the PVN surround. Further, in response to restraint stress, dual retrograde labeling with the cellular activation marker FOS suggests these PVN surround circuits are involved in adaptive responses to emotional stress. Of the PVN surround subregions, the zona incerta (ZI) showed particularly dense connectivity with the medial prefrontal cortex (mPFC), lateral septum, and paraventricular thalamus. Due to the strength of this connectivity we sought to confirm that it can act as a relay site to the PVN through targeted injections of anterograde tracer. ZI injections of anterograde tracer led to terminally labeled fibers in the PVN confirming the capacity to influence hypophysiotropic neurons of the PVN. Additionally, there is the potential for the ZI to share functional cross-talk with other PVN surround subregions. In our final experiment we directed injections of retrograde tracer into the PVN in concert with anterograde injections in the mPFC resulting in convergence of tracer labeling within the ZI. The abutted signals strongly indicate the PVN surround is a promising site for limbic influence on HPA.

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