In a series of experiments in brain slices and in mice, the researchers examined the organization and stability of inputs to hypocretin cell bodies, which act as filters in other brain cells. They found that hypocretin neurons have an "unorthodox" organization in which excitatory currents exert control on nerve cell bodies with minimal inhibitory inputs to filter them.

Overnight food deprivation promoted the formation of more excitatory inputs. Those new inputs were reversed upon refeeding, they reported, an indication of the extreme plasticity of the hypocretin system to prevailing conditions.

That sensitivity and adaptability makes sense, given the neurons' role as the body's natural alarm, rousing one from slumber in response to external cues, Horvath said. However, the structure of the system might also explain the prevalence of sleep disorders and, perhaps, the associated rise in obesity.

"In an evolutionary sense, the response of the hypocretin system to small stimuli would have been necessary for survival," he said. "But in today's chronically stressful environment, the circuitry may also be an underlying cause of insomnia and associated metabolic disturbances, including obesity."

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Contact: Heidi Hardman
hhardman@cell.com
1-617-397-2879
Cell Press
12-Apr-2005