Neuronal Activity in the Preoptic Hypothalamus During Sleep

34 The preoptic hypothalamus is implicated in sleep regulation. Neurons in the median 35 preoptic nucleus (MnPO) and the ventrolateral preoptic area (VLPO) have been 36 identified as potential sleep regulatory elements. However, the extent to which MnPO 37 and VLPO neurons are activated in response to changing homeostatic sleep regulatory 38 demands is unresolved. To address this question, we continuously recorded the 39 extracellular activity of neurons in the rat MnPO, VLPO and dorsal lateral preoptic area 40 (LPO) during baseline sleep and waking, during 2 h of sleep deprivation (SD) and 41 during 2 h of recovery sleep (RS). Sleep-active neurons in the MnPO (n=11) and 42 VLPO (n=13) were activated in response to SD, such that waking discharge rates 43 increased by 95.8%±29.5% and 59.4±17.3%, respectively, above waking baseline 44 values. During RS, nonREM sleep discharge rates of MnPO neurons initially increased 45 to 65.6±15.2% above baseline values, then declined to baseline levels in association 46 with decreases in EEG delta power. Increase in nonREM sleep discharge rates in 47 VLPO neurons during RS averaged 40.5±7.6% above baseline. REM-active neurons 48 (n=16) in the LPO also exhibited increased waking discharge during SD and an 49 increase in nonREM discharge during RS. Infusion of A 2A adenosine receptor 50 antagonist into the VLPO, attenuated SD-induced increases in neuronal discharge. 51 Populations of LPO wake/REM-active and state-indifferent neurons and dorsal LPO 52 sleep-active neurons were unresponsive to SD. These findings support the hypothesis 53 that sleep-active neurons in the MnPO and VLPO, and REM-active neurons in the LPO 54 are components of neuronal circuits that mediate homeostatic responses to sustained 55 wakefulness.