PMID- 16364907
OWN - NLM
STAT- MEDLINE
DCOM- 20060224
LR  - 20190508
IS  - 0896-6273 (Print)
IS  - 1097-4199 (Electronic)
IS  - 0896-6273 (Linking)
VI  - 48
IP  - 6
DP  - 2005 Dec 22
TI  - Integration of endocannabinoid and leptin signaling in an appetite-related neural 
      circuit.
PG  - 1055-66
AB  - Recently developed therapeutics for obesity, targeted against cannabinoid 
      receptors, result in decreased appetite and sustained weight loss. Prior studies 
      have demonstrated CB1 receptors (CB1Rs) and leptin modulation of cannabinoid 
      synthesis in hypothalamic neurons. Here, we show that depolarization of 
      perifornical lateral hypothalamus (LH) neurons elicits a CB1R-mediated 
      suppression of inhibition in local circuits thought to be involved in appetite 
      and "natural reward." The depolarization-induced decrease in inhibitory tone to 
      LH neurons is blocked by leptin. Leptin inhibits voltage-gated calcium channels 
      in LH neurons via the activation of janus kinase 2 (JAK2) and of 
      mitogen-activated protein kinase (MAPK). Leptin-deficient mice are characterized 
      by both an increase in steady-state voltage-gated calcium currents in LH neurons 
      and a CB1R-mediated depolarization-induced suppression of inhibition that is 
      6-fold longer than that in littermate controls. Our data provide direct 
      electrophysiological support for the involvement of endocannabinoids and leptin 
      as modulators of hypothalamic circuits underlying motivational aspects of feeding 
      behavior.
FAU - Jo, Young-Hwan
AU  - Jo YH
AD  - Department of Pathology and Cell Biology, Center for Neurobiology and Behavior, 
      Columbia University, College of Physicians and Surgeons, New York, New York 
      10032, USA. yjo@aecom.yu.edu
FAU - Chen, Ying-Jiun J
AU  - Chen YJ
FAU - Chua, Streamson C Jr
AU  - Chua SC Jr
FAU - Talmage, David A
AU  - Talmage DA
FAU - Role, Lorna W
AU  - Role LW
LA  - eng
GR  - NS22061/NS/NINDS NIH HHS/United States
GR  - R01 NS022061-21/NS/NINDS NIH HHS/United States
GR  - R01 NS022061-22/NS/NINDS NIH HHS/United States
GR  - R01 DK057621/DK/NIDDK NIH HHS/United States
GR  - R01 NS022061/NS/NINDS NIH HHS/United States
GR  - R01 NS022061-23/NS/NINDS NIH HHS/United States
GR  - CA79737/CA/NCI NIH HHS/United States
GR  - DK57621/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neuron
JT  - Neuron
JID - 8809320
RN  - 0 (Calcium Channels)
RN  - 0 (Cannabinoid Receptor Modulators)
RN  - 0 (Endocannabinoids)
RN  - 0 (Leptin)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptor, Cannabinoid, CB1)
RN  - 0 (Receptors, Leptin)
RN  - 0 (leptin receptor, mouse)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Jak2 protein, mouse)
RN  - EC 2.7.10.2 (Janus Kinase 2)
SB  - IM
MH  - Animals
MH  - Appetite Regulation/drug effects/*physiology
MH  - Calcium Channels/drug effects/metabolism
MH  - Calcium Signaling/drug effects/genetics
MH  - Cannabinoid Receptor Modulators/*metabolism/pharmacology
MH  - *Endocannabinoids
MH  - Hypothalamic Area, Lateral/drug effects/*metabolism
MH  - Hypothalamus/drug effects/physiology
MH  - Janus Kinase 2
MH  - Leptin/genetics/*metabolism/pharmacology
MH  - MAP Kinase Signaling System/drug effects/physiology
MH  - Membrane Potentials/drug effects/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Motivation
MH  - Neural Inhibition/drug effects/physiology
MH  - Neural Pathways/drug effects/*metabolism
MH  - Neurons/drug effects/metabolism
MH  - Organ Culture Techniques
MH  - Patch-Clamp Techniques
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Receptor, Cannabinoid, CB1/antagonists & inhibitors/metabolism
MH  - Receptors, Leptin
MH  - Reward
MH  - Signal Transduction/drug effects/*physiology
MH  - Time Factors
PMC - PMC2280039
MID - NIHMS40547
EDAT- 2005/12/21 09:00
MHDA- 2006/02/25 09:00
PMCR- 2008/04/03
CRDT- 2005/12/21 09:00
PHST- 2005/03/17 00:00 [received]
PHST- 2005/07/22 00:00 [revised]
PHST- 2005/10/05 00:00 [accepted]
PHST- 2005/12/21 09:00 [pubmed]
PHST- 2006/02/25 09:00 [medline]
PHST- 2005/12/21 09:00 [entrez]
PHST- 2008/04/03 00:00 [pmc-release]
AID - S0896-6273(05)00886-X [pii]
AID - 10.1016/j.neuron.2005.10.021 [doi]
PST - ppublish
SO  - Neuron. 2005 Dec 22;48(6):1055-66. doi: 10.1016/j.neuron.2005.10.021.