Relaxin family peptide receptor 3 (RXFP3) expressing cells in the zona incerta/lateral hypothalamus augment behavioural arousal.

Autor: Richards BK; The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.; Florey Department of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.; School of Psychological Sciences, Macquarie University, North Ryde, New South Wales, Australia., Ch'ng SS; The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.; Florey Department of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia., Simon AB; The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.; Florey Department of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia., Pang TY; The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.; Florey Department of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.; Institute of Health and Sports (IHES), Victoria University, Footscray, Victoria, Australia., Kim JH; The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.; Florey Department of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.; IMPACT-The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia., Lawrence AJ; The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.; Florey Department of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia., Perry CJ; The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.; Florey Department of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.; School of Psychological Sciences, Macquarie University, North Ryde, New South Wales, Australia.
Jazyk: angličtina
Zdroj: Journal of neurochemistry [J Neurochem] 2024 Sep 04. Date of Electronic Publication: 2024 Sep 04.
DOI: 10.1111/jnc.16217
Abstrakt: Fear-related psychopathologies, such as post-traumatic stress disorder, are linked to dysfunction in neural circuits that govern fear memory and arousal. The lateral hypothalamus (LH) and zona incerta (ZI) regulate fear, but our understanding of the precise neural circuits and cell types involved remains limited. Here, we examined the role of relaxin family peptide receptor 3 (RXFP3) expressing cells in the LH/ZI in conditioned fear expression and general arousal in male RXFP3-Cre mice. We found that LH/ZI RXFP3+ (LH/ZI RXFP3 ) cells projected strongly to fear learning, stress, and arousal centres, notably, the periaqueductal grey, lateral habenula, and nucleus reuniens. These cells do not express hypocretin/orexin or melanin-concentrating hormone but display putative efferent connectivity with LH hypocretin/orexin+ neurons and dopaminergic A13 cells. Following Pavlovian fear conditioning, chemogenetically activating LH/ZI RXFP3 cells reduced fear expression (freezing) overall but also induced jumping behaviour and increased locomotor activity. Therefore, the decreased freezing was more likely to reflect enhanced arousal rather than reduced fear. Indeed, stimulating these cells produced distinct patterns of coactivation between several motor, stress, and arousal regions, as measured by Fos expression. These results suggest that activating LH/ZI RXFP3 cells generates brain-wide activation patterns that augment behavioural arousal.
(© 2024 The Author(s). Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)
Databáze: MEDLINE
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