Molecular Approach to Hypothalamic Rhythms
Abstract
We have identified 4 new CNS receptors for the circadian phase-resetting indoleamine neurotransmitter serotonin: 5-HT1F' 5-HT5A' 5-HT5B and 5-HT7. We found that the 5-HT5A receptor is located predominantly on astrocytes throughout the CNS, while the 5-HT7 receptor, which we have directly implicated in circadian phase-shifting, is located in the region of the suprachiasmatic nucleus that receives the primary retinal innervation. We have generated knock-out mice null for the 5-HT7 gene, but this mutation proved lethal when homozygous, hence we are unable to establish a genetic test its involvement in the mature nervous system. However, we have shown that this receptor is expressed in the thalamus and hypothalamus in the same neurons; that are transcriptionally activated by the sleep-inducing lipid oleamide. We have characterized new neuropeptides, two (the hypocretins) expressed from a common precursor exclusively by a previously unrecognized nucleus within the hypothalamus, and another (cortistatin) expressed predominanyly by cortical and hippocampal interneurons that affects the onset of slow-wave sleep. To learn about the cellular mechanisms of entrainment, we have developed a new PCR-based methodology to identify mRNA molecules whose expression is specifically enriched in the SCN or whose accumulation there is stimulated by an entraining pulse of light, using RNA extracted from punched SCN tissue. The method has now been completely automated and has been coupled with a powerful bioinformatics network.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 24, 1998
- Accession Number
- ADA348785
Entities
People
- J. G. Sutcliffe
Organizations
- Scripps Research