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Submitted on August 17, 2005
Accepted on September 22, 2005
Netherlands Institute for Brain Research, Meibergdreef 33, Amsterdam, The Netherlands; Tongji Medical College of Huazhong University of Science and Technology, 13 Hangkong Rd. Wuhan, P.R. China
* To whom correspondence should be addressed. E-mail: c.yi{at}nih.knaw.nl.
The arcuate nucleus (ARC) is crucial for the maintenance of energy homeostasis as an integrator of long- and short-term hunger and satiety signals. Expression of receptors for metabolic hormones, such as insulin, leptin and ghrelin, allows ARC to sense information from the periphery and signal it to the central nervous system. The ventromedial ARC (vmARC) mainly comprises orexigenic neuropeptide AGRP and NPY neurons, which are sensitive to circulating signals. To investigate neural connections of vmARC within the central nervous system, we injected the neuronal tracer cholera toxin B into vmARC. Due to variation of injection sites, tracer was also injected into the subependymal layer of the median eminence (seME) which showed similar projection patterns as the vmARC. We propose that the vmARC forms a complex with the seME, their reciprocal connections with viscerosensory areas in brain stem and other circumventricular organs suggesting exchange of metabolic and circulating information. For the first time the vmARC-seMe was shown to have reciprocal interaction with the suprachiasmatic nucleus (SCN). Activation of vmARC neurons by systemic administration of the ghrelin mimetic GHRP-6 combined with SCN tracing showed vmARC neurons to transmit feeding related signals to the SCN. The functionality of this pathway was demonstrated by systemic injection of GHRP-6, which induced Fos in the vmARC, and resulted in a reduction of about 40% of early daytime Fos immunoreactivity in the SCN. This observation suggests an anatomical and functional pathway for peripheral hormonal feedback to the hypothalamus, which may serve to modulate the activity of the SCN.
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