Universität zu Köln

Todd, William D., Fenselau, Henning, Wang, Joshua L., Zhang, Rong ORCID: 0000-0001-7906-6210, Machado, Natalia L., Venner, Anne ORCID: 0000-0001-7481-3248, Broadhurst, Rebecca Y., Kaur, Satvinder, Lynagh, Timothy ORCID: 0000-0003-4888-4098, Olson, David P., Lowell, Bradford B., Fuller, Patrick M. and Saper, Clifford B. (2018). A hypothalamic circuit for the circadian control of aggression. Nat. Neurosci., 21 (5). S. 717 - 728. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1546-1726

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Abstract

'Sundowning' in dementia and Alzheimer's disease is characterized by early-evening agitation and aggression. While such periodicity suggests a circadian origin, whether the circadian clock directly regulates aggressive behavior is unknown. We demonstrate that a daily rhythm in aggression propensity in male mice is gated by GABAergic subparaventricular zone (SPZ(GABA)) neurons, the major postsynaptic targets of the central circadian clock, the suprachiasmatic nucleus. Optogenetic mapping revealed that SPZ(GABA) neurons receive input from vasoactive intestinal polypeptide suprachiasmatic nucleus neurons and innervate neurons in the ventrolateral part of the ventromedial hypothalamus (VMH), which is known to regulate aggression. Additionally, VMH-projecting dorsal SPZ neurons are more active during early day than early night, and acute chemogenetic inhibition of SPZ(GABA) transmission phase-dependently increases aggression. Finally, SPZ(GABA)-recipient central VMH neurons directly innervate ventrolateral VMH neurons, and activation of this intra-VMH circuit drove attack behavior. Altogether, we reveal a functional polysynaptic circuit by which the suprachiasmatic nucleus clock regulates aggression.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Todd, William D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fenselau, Henning UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Joshua L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhang, Rong UNSPECIFIED orcid.org/0000-0001-7906-6210 UNSPECIFIED Machado, Natalia L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Venner, Anne UNSPECIFIED orcid.org/0000-0001-7481-3248 UNSPECIFIED Broadhurst, Rebecca Y. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaur, Satvinder UNSPECIFIED UNSPECIFIED UNSPECIFIED Lynagh, Timothy UNSPECIFIED orcid.org/0000-0003-4888-4098 UNSPECIFIED Olson, David P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lowell, Bradford B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fuller, Patrick M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Saper, Clifford B. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-187116
DOI:	10.1038/s41593-018-0126-0
Journal or Publication Title:	Nat. Neurosci.
Volume:	21
Number:	5
Page Range:	S. 717 - 728
Date:	2018
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	NEW YORK
ISSN:	1546-1726
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SUPRACHIASMATIC NUCLEUS; SUBPARAVENTRICULAR ZONE; PARAVENTRICULAR NUCLEUS; GABAERGIC NEURONS; EFFERENT PROJECTIONS; DEMENTIA; SLEEP; BEHAVIORS; TRANSPORT; OUTPUT Multiple languages Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18711