The proposed research combines electrophysiological recordings and immunohistochemistry to study hypothalamic neuronal networks that regulate body temperature and fever. The study focuses on the preoptic area and anterior hypothalamus, a region containing thermosensitive neurons that not only sense brain temperature but also receive afferent inputs from peripheral thermoreceptors. These neurons integrate central and peripheral temperatures, and they are believed to be responsible for a variety of physiological and behavioral responses that control body temperature. Responses include skin blood flow, evaporative heat loss (e.g., salivation/skin wetting, panting, sweating), shivering and non-shivering thermogenesis (via metabolic hormones and brown adipose tissue). Moreover, cytokines affect preoptic neurons to produce fever, and it is likely that reproductive hormones affect these same neurons to produce menopausal hot flushes and phase changes in body temperature during the menstrual cycle. Thus, this research explores a neuronal network that controls several crucial, interrelated systems. Our studies have identified at least five neuronal types; and the proposal presents models describing how these neurons may form synaptic networks controlling thermoregulatory responses. In the proposed experiments, intracellular microelectrodes record the action potentials and synaptic activity of neurons in rat hypothalamic tissue slices. Excitatory and inhibitory synaptic events are recorded during current- and voltage-clamp conditions. For each neuronal type, neurotransmitters are studied using selective antagonists and immunohistochemistry, and axonal pathways are identified using retrograde tracers.
Aim 1 tests and expands the models by characterizing different neurons according to their physiological properties, dendritic orientations and endogenous neurochemicals.
Aim 2 examines hypothalamic synaptic I networks: (a) by characterizing the thermosensitivity of presynaptic neurons; and (b) by identifying neurotransmitters and their receptors using specific antagonists and immunohistochemistry.
Aim 3 uses retrograde tracers to examine axonal projections to midbrain effector sites. The overall goal is to identify hypothalamic networks by characterizing neurons according to their physiological responses, dendritic morphologies, synaptic inputs and axonal projections.
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