Local Corticotropin-Releasing Factor Signaling in the Hypothalamic Paraventricular Nucleus.
TLDR
In this article, the authors characterize the electrophysiological and molecular properties of hypothalamic paraventricular nucleus-CRFR1 neurons and interrogate their monosynaptic connectivity using rabies virus-based tracing and optogenetic circuit mapping in male and female mice.Abstract:
Corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus (PVN) initiate hypothalamic-pituitary-adrenal axis activity through the release of CRF into the portal system as part of a coordinated neuroendocrine, autonomic, and behavioral response to stress. The recent discovery of neurons expressing CRF receptor type 1 (CRFR1), the primary receptor for CRF, adjacent to CRF neurons within the PVN, suggests that CRF also signals within the hypothalamus to coordinate aspects of the stress response. Here, we characterize the electrophysiological and molecular properties of PVN-CRFR1 neurons and interrogate their monosynaptic connectivity using rabies virus-based tracing and optogenetic circuit mapping in male and female mice. We provide evidence that CRF neurons in the PVN form synapses on neighboring CRFR1 neurons and activate them by releasing CRF. CRFR1 neurons receive the majority of monosynaptic input from within the hypothalamus, mainly from the PVN itself. Locally, CRFR1 neurons make GABAergic synapses on parvocellular and magnocellular cells within the PVN. CRFR1 neurons resident in the PVN also make long-range glutamatergic synapses in autonomic nuclei such as the nucleus of the solitary tract. Selective ablation of PVN-CRFR1 neurons in male mice elevates corticosterone release during a stress response and slows the decrease in circulating corticosterone levels after the cessation of stress. Our experiments provide evidence for a novel intra-PVN neural circuit that is activated by local CRF release and coordinates autonomic and endocrine function during stress responses.SIGNIFICANCE STATEMENT The hypothalamic paraventricular nucleus (PVN) coordinates concomitant changes in autonomic and neuroendocrine function to organize the response to stress. This manuscript maps intra-PVN circuitry that signals via CRF, delineates CRF receptor type 1 neuron synaptic targets both within the PVN and at distal targets, and establishes the role of this microcircuit in regulating hypothalamic-pituitary-adrenal axis activity.read more
Citations
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Journal ArticleDOI
Neurobiological links between stress and anxiety.
TL;DR: Circuits sharing subcortical nodes and underlying the processing of both stress and anxiety are revealed, and a new role for hypothalamic corticotropin-releasing hormone neurons in controlling anxiety-like and stress-induce behaviors is presented.
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Identification of a neurocircuit underlying regulation of feeding by stress-related emotional responses
Yuanzhong Xu,Yungang Lu,Ryan M. Cassidy,Leandra R. Mangieri,Canjun Zhu,Xugen Huang,Zhiying Jiang,Nicholas J. Justice,Yong Xu,Benjamin R. Arenkiel,Benjamin R. Arenkiel,Qingchun Tong +11 more
TL;DR: It is reported that projections from the paraventricular hypothalamus to the ventral part of the lateral septum regulates both feeding and behavioral responses to stress.
Journal ArticleDOI
CRF signaling between neurons in the paraventricular nucleus of the hypothalamus (PVN) coordinates stress responses.
TL;DR: Recent work characterizing an intra-PVN microcircuit in which locally released CRF release activates CRFR1+ neurons that make recurrent inhibitory GABAergic synapses onto CRF neurons to dampen excitability is reviewed, thereby limiting HPA axis hyperactivity in response to stress and promoting stress recovery.
Journal ArticleDOI
Roles for androgens in mediating the sex differences of neuroendocrine and behavioral stress responses.
TL;DR: The role of androgens in stress-related behaviors and HPA function has been explored in this paper, focusing on androgens as an important hormone for modulating the HPA axis and behaviors throughout life and for setting up sex differences in key stress regulatory systems that could impact risk for disease in adulthood.
Journal ArticleDOI
Paraventricular hypothalamic and amygdalar CRF neurons synapse in the external globus pallidus
Albert J. Hunt,Albert J. Hunt,Rajan Dasgupta,Rajan Dasgupta,Shivakumar Rajamanickam,Zhiying Jiang,Michael Beierlein,Michael Beierlein,C. Savio Chan,Nicholas J. Justice,Nicholas J. Justice +10 more
TL;DR: A novel neural circuit by which stress-relevant information carried by the limbic system signals in the GPe via CRF to influence motor output is described.
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