THE HYPOCRETINS - HYPOTHALAMUS-SPECIFIC PEPTIDES WITH NEUROEXCITATORYACTIVITY

We describe a hypothalamus-specific mRNA that encodes preprohypocretin , the putative precursor of a pair of peptides that share substantial amino acid identities with the gut hormone secretin, The hypocretin (H crt) protein products are restricted to neuronal cell bodies of the do rsal and lateral hypothalamic areas. The fibers of these neurons are w idespread throughout the posterior hypothalamus and project to multipl e targets in other areas, including brainstem and thalamus. Hcrt immun oreactivity is associated with large granular vesicles at synapses, On e of the Hcrt peptides was excitatory when applied to cultured, synapt ically coupled hypothalamic neurons, but not hippocampal neurons. Thes e observations suggest that the hypocretins function within the CNS as neurotransmitters.