As anyone who has had a cold recently can testify, the response to infection includes both a fever and drowsiness. And anyone who has tried to sleep through a hot, sticky summer night will realize that sleep and control of body temperature are intertwined. Recent work in the laboratory of Clifford Saper, in the Department of Neurology at Beth Israel Hospital, is beginning to make sense of this connection.
His group monitors the cell groups in the rodent brain that are turned on during physiological responses. By using carefully controlled physiological stimuli and watching for evidence of a protein called Fos, a product of the gene c-fos, expressed when neurons are activated, investigators can both monitor which neurons are activated and simultaneously determine the connections and neurotransmitters that are used.
Saper's group finds that, in a brain structure, the hypothalamus, known to command many automatic body functions, there are two adjacent cell groups that share many connections. One, the ventrolateral preoptic nucleus, seems to be responsible for sleep and, in fact, is the only cell group in the brain that shows Fos-activation during sleep. The other, the ventromedial preoptic area, is thought to be involved in thermoregulation/fever.
Studies of the two areas' connections suggest that both may use the same neurotransmitter, called GABA, one to inhibit the brain's arousal system, allowing sleep to occur, and the other to inhibit warm-sensitive cells that act as a thermostat. Activation of the ventromedial preoptic area can "fool" the thermostat into thinking body temperature is lower than it actually is, and cause excess heat production. Both cell groups are activated during fever caused by immune stimulation, producing the characteristic elevation of body
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