Certain rostral hypothalamic neurons sense their own temperature and receive afferent information about peripheral temperatures. This integrative neuronal network communicates with other hypothalamic and brain stem areas to control thermoregulatory responses, including cutaneous blood flow, evaporative heat loss (sweating, panting), shivering (muscle tremor), metabolic endocrines, and various behaviors. The neural control of these responses is dramatically affected by neural disease, lesions, drugs, and thermal stress. This network is also affected by fever-producing pyrogens, and during many disease states, it is important in evoking immune and acute phase responses. While previous studies reveal much about neuronal types and integration of thermal information, surprisingly little is known about the cellular basis of neuronal thermosensitivity. Using hypothalamic tissue slices, the immediate aim of this research is to understand inherent and synaptic mechanisms responsible for temperature sensitive and insensitive neurons. Our lone-term objective is to use this information to understand how endogenous substances (e.g., pyrogens) influence neurons regulating body temperature and other homeostatic systems. This is the first intracellular study of warm sensitive, cold sensitive. and temperature insensitive neurons in the mammalian hypothalamus. It tests hypotheses that inherent neuronal thermosensitivity is due to temperature dependent changes in membrane potential, pacemaker potential and excitability. To reveal mechanisms for these changes, input resistance will be studied and ionic conductances will be altered. Also, ouabain blockade of the Na-K pump will determine the pump's role in thermally-dependent changes in membrane characteristics, particularly in cold sensitive and temperature insensitive neurons. Finally, neurons showing delayed responses to temperature may be an important, but overlooked component of temperature regulation. Experiments will determine whether delayed thermal responses are due to synaptic mechanisms, the Na-K pump, or cyclic AMP.
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