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The Journal of Neuroscience, April 15, 1999, 19(8):3171-3182
Hypothalamic Hypocretin (Orexin): Robust Innervation of the
Spinal Cord
Anthony N.
van den Pol
Department of Neurosurgery, Yale University School of Medicine, New
Haven, Connecticut 06520
Hypocretin (orexin) is synthesized by neurons in the lateral
hypothalamus and has been reported to increase food intake and regulate
the neuroendocrine system. In the present paper, long descending axonal
projections that contain hypocretin were found that innervate all
levels of the spinal cord from cervical to sacral segments, as studied
in mouse, rat, and human spinal cord and not previously described. High
densities of axonal innervation are found in regions of the spinal cord
related to modulation of sensation and pain, notably in the marginal
zone (lamina 1). Innervation of the intermediolateral column and lamina
10 as well as strong innervation of the caudal region of the sacral
cord suggest that hypocretin may participate in the regulation of both the sympathetic and parasympathetic parts of the autonomic nervous system. Double-labeling experiments in mice combining retrograde transport of diamidino yellow after spinal cord injections and immunocytochemistry support the concept that hypocretin-immunoreactive fibers in the cord originate from the neurons in the lateral
hypothalamus. Digital-imaging physiological studies with fura-2
detected a rise in intracellular calcium in response to hypocretin in
cultured rat spinal cord neurons, indicating that spinal cord neurons
express hypocretin-responsive receptors. A greater number of cervical cord neurons responded to hypocretin than another hypothalamo-spinal neuropeptide, oxytocin. These data suggest that in addition to possible
roles in feeding and endocrine regulation, the descending hypocretin
fiber system may play a role in modulation of sensory input,
particularly in regions of the cord related to pain perception and
autonomic tone.
Key words:
hypothalamus; neuroendocrine; spinal cord; autonomic
nervous system; pain; food intake; energy regulation; lamina 1
Copyright © 1999 Society for Neuroscience 0270-6474/99/1983171-12$05.00/0
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