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An adaptive stress response involves various mediators and circuits orchestrating a complex interplay of physiological, emotional, and behavioral adjustments. We identified a population of corticotropin-releasing hormone (CRH) neurons in the lateral part of the interstitial nucleus of the anterior commissure (IPACL), a subdivision of the extended amygdala, which exclusively innervate the substantia nigra (SN). Specific stimulation of this circuit elicits hyperactivation of the hypothalamic-pituitary-adrenal axis, locomotor activation, and avoidance behavior contingent on CRH receptor type 1 (CRHR1) located at axon terminals in the SN, which originate from external globus pallidus (GPe) neurons. The neuronal activity prompting the observed behavior is shaped by IPACL and GPe neurons coalescing in the SN. These results delineate a previously unidentified tripartite CRH circuit functionally connecting extended amygdala and basal ganglia nuclei to drive locomotor activation and avoidance behavior.
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http://dx.doi.org/10.1126/sciadv.abo1023 | DOI Listing |
Elife
September 2025
Department of Psychiatry & Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, United States.
Fragile X syndrome (FXS), a leading inherited cause of intellectual disability and autism, is frequently accompanied by sleep and circadian rhythm disturbances. In this study, we comprehensively characterized these disruptions and evaluated the therapeutic potential of a circadian-based intervention in the fragile X mental retardation 1 () knockout (KO) mouse. The KO mice exhibited fragmented sleep, impaired locomotor rhythmicity, and attenuated behavioral responses to light, linked to an abnormal retinal innervation and reduction of light-evoked neuronal activation in the suprachiasmatic nucleus.
View Article and Find Full Text PDFAnn Neurol
September 2025
Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Zurich, Switzerland.
Objective: Impaired ability to induce stepping after incomplete spinal cord injury (SCI) can limit the efficacy of locomotor training, often leaving patients wheelchair-bound. The cuneiform nucleus (CNF), a key mesencephalic locomotor control center, modulates the activity of spinal locomotor centers via the reticulospinal tract. Even with severe corticospinal damage, the widely distributed reticulospinal fibers frequently cross the lesion, and lumbosacral spinal locomotor centers remain responsive.
View Article and Find Full Text PDFAlpha Psychiatry
August 2025
Department of Pharmacology, School of Pharmaceutical Science, Ohu University, Koriyama, 963-8611 Fukushima, Japan.
Objective: Hypothalamic‒pituitary‒adrenal axis response is essential for coping with acute stressors, while maladaptive stress coping may increase the risk of major depressive disorder. We previously demonstrated that behavioral patterns induced by prior psychological stress predict coping levels in response to future stressors. This study investigated whether activating corticotropin-releasing hormone (CRH) and corticosteroid receptors mediates psychological stress-induced coping behavior.
View Article and Find Full Text PDFComp Biochem Physiol C Toxicol Pharmacol
September 2025
Occupational Health, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126, Ancona, Italy. Electronic address:
Artificial light at night (ALAN) can disrupt numerous biological processes, and is increasingly studied in animal models. Here, we evaluated the impact of red and blue ALAN on Drosophila melanogaster, focusing on fertility, development, circadian rhythms, and gene expression. All results were compared to those of a control group maintained under a 12 h white light/12 h dark cycle.
View Article and Find Full Text PDFFront Neurosci
August 2025
Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Introduction: Siestas, or daytime naps, play a critical role in relieving sleep pressure and maintaining physiological balance. However, the effects of siesta disruption remain largely unexplored.
Methods: In this study, we disrupted the natural siesta period (ZT20-23) through daily bedding changes for 2 weeks and examined its effects on overall stress levels, sleep architecture, behavior, and transcriptional responses in the frontal cortex.