Hypocretin (orexin) is a recently discovered neuropeptide synthesized by lateral hypothalamic area neurons that project widely throughout the brain and spinal cord. Functionally, hypocretin may play a key role in activation of many brain circuits related to attention, waking, or arousal. Absence of hypocretin or its hypocretin-2 receptor causes narcolepsy, a clinical condition characterized by short unexpected periods of sleep, both in animals and humans. A growing number of functional studies have shown that hypocretin may also modulate feeding, influence neuroendocrine neurons, alter blood pressure, and cellular physiology of the hypocretin cells. To facilitate the study of hypocretin neuron neurophysiology, we will use transgenic mice that express green fluorescent protein selectively in live hypocretin-acid transmitter will be studied with whole cell recording in cultured neurons and in hypothalamic slices. To facilitate the study of hypocretin neuron neurophysiology, synthesizing neurons. The hypothesis that hypocretin cells use glutamate as a primary fast-acting amino acid transmitter will be used with whole cell recording in cultured neurons and in hypothalamic slices. Hypocretin projects originating in the LH are found throughout the brain, including a dense local projection to the LH area where hypocretin axons make synaptic contact with hypocretin neurons. The hypothesis that hypocretin may excite hypocretin cells, potentially serving a positive feedback role in modulation of hypocretin cells, potentially serving a positive feedback role in modulation of hypocretin cells and pre-synaptic modulation of GABA and glutamate axons that innervate hypocretin neurons will be studied. Active and passive membrane properties of hypocretin neurons, concentrating hormone (MHC) is the other major neuropeptide found in cells interspersed with hypocretin neurons in the LH area. The hypothesis that MHC neurons make synaptic contact with hypocretin neurons in the LH area. The hypothesis that MCH neurons make synaptic contact with hypocretin, homeostasis, and may be the glucose-sensitive neurons of the LH, will be examined. Together, these experiments will provide a better understanding of the cellular mechanisms underlying hypocretin actions and neuronal communication to and from hypocretin neurons.
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