NDLI: A Novel Excitatory Paraventricular Nucleus to AgRP Neuron Circuit that Drives Hunger

Content Provider	PubMed Central
Author	Krashes, Michael J. Shah, Bhavik P. Madara, Joseph C. Olson, David P. Strochlic, David E. Garfield, Alastair S. Vong, Linh Pei, Hongjuan Watabe-uchida, Mitsuko Uchida, Naoshige Liberles, Stephen D. Lowel, Bradford B.
Abstract	Hunger is a hard-wired motivational state essential for survival. Agouti-related peptide (AgRP)-expressing neurons in the arcuate nucleus (ARC) at the base of the hypothalamus are crucial to its control. They are activated by caloric deficiency and, when naturally or artificially stimulated, they potently induce intense hunger and subsequent food intake 1-5 . Consistent with their obligatory role in regulating appetite, genetic ablation or pharmacogenetic inhibition of AgRP neurons decreases feeding 3,6,7 . Excitatory input to AgRP neurons is key in caloric-deficiency-induced activation, and is notable for its remarkable degree of caloric state-dependent synaptic plasticity 8-10 . Despite the important role of excitatory input, its source(s) has been unknown. Here, through the use of Cre-recombinase-enabled, cell-specific neuron mapping techniques, we have discovered strong excitatory drive that, unexpectedly, emanates from the hypothalamic paraventricular nucleus, specifically from subsets of neurons expressing Thyrotropin-releasing hormone (TRH) and Pituitary adenylate cyclase-activating polypeptide (PACAP). Pharmaco-genetic stimulation of these afferent neurons in sated mice markedly activates AgRP neurons and induces intense feeding. Conversely, acute inhibition in mice with caloric deficiency-induced hunger decreases feeding. Discovery of these afferent neurons capable of triggering hunger advances understanding of how this intense motivational state is regulated.
Related Links	http://dx.doi.org/10.1038/nature12956
Ending Page	242
Page Count	5
Starting Page	238
File Format	PDF
ISSN	00280836
e-ISSN	14764687
Journal	Nature
Issue Number	7491
Volume Number	507
Language	English
Publisher Date	2014-02-01
Access Restriction	Open
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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