Publication Date:
2001-12-26
Description:
The circadian clock in the suprachiasmatic nucleus (SCN) is thought to drive daily rhythms of behavior by secreting factors that act locally within the hypothalamus. In a systematic screen, we identified transforming growth factor-alpha (TGF-alpha) as a likely SCN inhibitor of locomotion. TGF-alpha is expressed rhythmically in the SCN, and when infused into the third ventricle it reversibly inhibited locomotor activity and disrupted circadian sleep-wake cycles. These actions are mediated by epidermal growth factor (EGF) receptors on neurons in the hypothalamic subparaventricular zone. Mice with a hypomorphic EGF receptor mutation exhibited excessive daytime locomotor activity and failed to suppress activity when exposed to light. These results implicate EGF receptor signaling in the daily control of locomotor activity, and identify a neural circuit in the hypothalamus that likely mediates the regulation of behavior both by the SCN and the retina.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kramer, A -- Yang, F C -- Snodgrass, P -- Li, X -- Scammell, T E -- Davis, F C -- Weitz, C J -- HD-18686/HD/NICHD NIH HHS/ -- MH62589/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2001 Dec 21;294(5551):2511-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11752569" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Biological Clocks/drug effects/physiology
;
Body Temperature/drug effects
;
Cerebral Ventricles/metabolism
;
Circadian Rhythm/drug effects/*physiology
;
Cricetinae
;
Darkness
;
Epidermal Growth Factor/pharmacology
;
Female
;
Hypothalamus/*metabolism
;
Ligands
;
Light
;
Male
;
Mesocricetus
;
Mice
;
*Motor Activity/drug effects
;
Neural Pathways/physiology
;
Neurons/metabolism
;
Point Mutation
;
Receptor, Epidermal Growth Factor/genetics/*metabolism
;
Retina/metabolism
;
Retinal Ganglion Cells/metabolism
;
Signal Transduction
;
Sleep/drug effects/*physiology
;
Suprachiasmatic Nucleus/*metabolism
;
Transforming Growth Factor alpha/administration &
;
dosage/genetics/metabolism/pharmacology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
