The central nervous system orchestrates the regulation of body temperature within a narrow range to optimize cellular function and facilitate homeostasis. The neural networks mediating thermoregulatory compensations for a cold external environment include the afferent pathway for cutaneous cold, thermoregulatory integrative sites in the preoptic area and hypothalamus and descending pathways to spinal neurons controlling effector function. We have conducted a series of anatomical and in vivo electrophysiological studies to elucidate central thermoregulatory networks. Experiments were conducted on rats anesthetized intravenously with urethane (0.8g/kg) and chloralose (70 mg/kg) and under neuromuscular blockade with d-tubocurarine (0.2mg/hr), during which, adequacy of anesthesia was monitored as described(3). Here we describe the feedforward reflex pathway underlying the stimulation of thermogenesis in brown adipose tissue (BAT) in response to skin cooling. The presence of uncoupling protein in the mitochondrial membrane of brown adipocytes allows them to respond to their sympathetic neural input by generating heat through fatty acid oxidation. Cutaneous cold signals, sensed by TRP channels in thermal receptor membranes, excite cool-responsive neurons in the spinal dorsal horn that provide a glutamatergic excitation to neurons in the lateral parabrachial nucleus(6). Lateral parabrachial neurons excited by skin cooling send their axons primarily to the median preoptic nucleus (MnPO)(6) where they excite GABAergic interneurons that reduce the activity of warm-responsive neurons in the medial preoptic area. The discharge of warm-responsive neurons in the preoptic area is increased as local brain temperature rises(1) and this core temperature information is integrated with inhibitory synaptic input from the cutaneous cold afferent pathway and excitatory synaptic drive from cutaneous warm afferents to produce a preoptic area efferent signal that inhibits cold defense mechanisms, including BAT thermogenesis(2). Thus, stimulation of BAT thermogenesis in response to skin cooling involves disinhibition of the sympathoexcitatory drive to BAT preganglionic neurons. Potential targets of the inhibitory projection neurons in the preoptic area are the dorsomedial hypothalamus (DMH) and the rostral raphe pallidus (rRPa): (a) both sites receive direct projections from the preoptic area, (b) blockade of GABA_A receptors in either the DMH or the rRPa stimulates BAT thermogenesis and (c) blockade of glutamate receptors in either site eliminates skin cooling-evoked increases in BAT sympathetic nerve activity (SNA)(4,5,7). The rRPa and the neighboring parapyramidal area contain BAT sympathetic premotor neurons whose activity is necessary for activation of BAT thermogenesis, including that evoked from the DMH, which sends a direct projection to the rRPa(7). At least some BAT sympathetic premotor neurons in rRPa contain serotonin and spinal serotonin release can augment the level of BAT SNA by potentiating the glutamate receptor-mediated excitation of BAT sympathetic preganglionic neurons(3). In summary, the cutaneous cold afferent pathway involves dorsal horn, lateral parabrachial nucleus and MnPO neurons that act to inhibit warm-responsive inhibitory projection neurons in the medial preoptic area which allows increased activity in an efferent pathway involving DMH neurons, BAT premotor neurons in rRPa and BAT sympathetic preganglionic neurons that drives a feedforward increase in BAT thermogenesis to prevent a fall in brain and core body temperatures.