Characteristics of Sleep-Active Neurons in the Medullary Parafacial Zone in Rats.

Growing evidence supports a role for the medullary parafacial zone in non-rapid eye movement (nonREM) sleep regulation. Cell-body specific lesions of the parafacial zone or disruption of its GABAergic/glycinergic transmission causes suppression of nonREM sleep, whereas, targeted activation of parafacial GABAergic/glycinergic neurons reduce sleep latency and increase nonREM sleep amount, bout duration, and cortical EEG slow-wave activity. Parafacial GABAergic/glycinergic neurons also express sleep-associated c-fos immunoreactivity. Currently, it is not clear if parafacial neurons are nonREM sleep-active and/or REM sleep-active or play a role in the initiation or maintenance of nonREM sleep. We recorded extracellular discharge activity of parafacial neurons across the spontaneous sleep-waking cycle using microwire technique in freely behaving rats. Waking-, nonREM sleep-, and REM sleep-active neuronal groups were segregated by the ratios of their discharge rate changes during nonREM- and REM-sleep versus waking and nonREM sleep versus REM sleep. Parafacial neurons exhibited heterogeneity in sleep-waking discharge patterns, but 34 of 86 (40%) recorded neurons exhibited increased discharge rate during nonREM sleep compared to waking. These neurons also exhibited increased discharge prior to nonREM sleep onset, similar to median preoptic nucleus (MnPO) and ventrolateral preoptic area (VLPO) sleep-active neurons. However, unlike MnPO and VLPO sleep-active neurons, parafacial neurons were weakly-moderately sleep-active and exhibited a stable rather than decreasing discharge across sustained nonREM sleep episode. We show for the first time that the medullary parafacial zone contains nonREM sleep-active neurons. These neurons are likely functionally important brainstem compliments to the preoptic-hypothalamic sleep-promoting neuronal networks that underlie sleep onset and maintenance.