Optogenetic activation of GABAergic PZ neurons induces cortical slow-wave activity and slow-wave sleep in awake animals.[1] In cases of genetic disruption of GABAergic transmizzion from PZ in mice, the mice were observed to go through periods of significantly longer, sustained wakefulness.[7] PZ neurons are also believed to be sleep active, as they express c-Fos after sleep but not after wakefulness.[1][8]
The parafacial is located within the medulla oblongata, lateral and dorsal to the facial nerve.[8] It overlaps with the alpha part of the parvocellular reticular formation (PCRt), which is thought to govern states of consciousness as well as have some control over sleep-wake sensory signals and mechanisms. However, PZ and PCRt activity are believed to be of separate nature.
Inputs
The parafacial zone receives inputs mainly from three areas: the hypothalamus, the midbrain, and the pons and medulla.[9]
From the hypothalamus, the PZ receives inputs from the hypothalamic area, zona incerta, and the parasubthalamic nucleus; while the zona incerta and parasubthalamic nucleus functions remain largely unknown, several of their functions have been proposed to deal with action selection and limbic-motor integration.
From the midbrain, the PZ receives input from the substantia nigra, pars reticulata, and deep mesencephalic nucleus. These brain structures are believed to deal heavily with movement, as well as reward and unconscious reflex; additionally, the par reticulata especially has been documented to project nearly all GABAergic inhibitory neurons. And from the pons and medulla, the PZ receives input from the intermediate reticular nucleus and medial vestibular nucleus (parvocellular), areas that are thought to be involved in expiration and respiratory rhythm generation.
Thirty-four various nuclei also share strong reciprocal projections with PZ GABAergic neurons, including various nuclei of the stria terminalis, the lateral hypothalamic area, the substantia nigra, the zona incerta, and the central amygdaloid nucleus.[9] These strong reciprocal projections suggest feedback control and the ability to regulate specific functions.
^ abcdefAnaclet C, Ferrari L, Arrigoni E, Bass CE, Saper CB, Lu J, Fuller PM (September 2014). "The GABAergic parafacial zone is a medullary slow wave sleep-promoting center"(PDF). Nat. Neurosci. 17 (9): 1217–1224. doi:10.1038/nn.3789. PMC4214681. PMID25129078. In the present study we show, for the first time, that activation of a delimited node of GABAergic neurons located in the medullary PZ can potently initiate SWS and cortical SWA in behaving animals. ... For now however it remains unclear if the PZ is interconnected with other sleep– and wake–promoting nodes beyond the wake–promoting PB. ... The intensity of cortical slow–wave–activity (SWA: 0.5–4Hz) during SWS is also widely accepted as a reliable indicator of sleep need ... In conclusion, in the present study we demonstrated that all polygraphic and neurobehavioral manifestation of SWS, including SWA, can be initiated in behaving animals by the selective activation of a delimited node of GABAergic medullary neurons.
^ abcSchwartz MD, Kilduff TS (December 2015). "The Neurobiology of Sleep and Wakefulness". The Psychiatric Clinics of North America. 38 (4): 615–644. doi:10.1016/j.psc.2015.07.002. PMC4660253. PMID26600100. This ascending reticular activating system (ARAS) is comprised of cholinergic laterodorsal and pedunculopontine tegmentum (LDT/PPT), noradrenergic locus coeruleus (LC), serotonergic (5-HT) Raphe nuclei and dopaminergic ventral tegmental area (VTA), substantia nigra (SN) and periaqueductal gray projections that stimulate the cortex directly and indirectly via the thalamus, hypothalamus and BF.6, 12-18 These aminergic and catecholaminergic populations have numerous interconnections and parallel projections which likely impart functional redundancy and resilience to the system.6, 13, 19 ... More recently, the medullary parafacial zone (PZ) adjacent to the facial nerve was identified as a sleep-promoting center on the basis of anatomical, electrophysiological and chemo- and optogenetic studies.23, 24 GABAergic PZ neurons inhibit glutamatergic parabrachial (PB) neurons that project to the BF,25 thereby promoting NREM sleep at the expense of wakefulness and REM sleep. ... Sleep is regulated by GABAergic populations in both the preoptic area and the brainstem; increasing evidence suggests a role for the melanin-concentrating hormone cells of the lateral hypothalamus and the parafacial zone of the brainstem
^ abCherasse Y, Urade Y (November 2017). "Dietary Zinc Acts as a Sleep Modulator". International Journal of Molecular Sciences. 18 (11): 2334. doi:10.3390/ijms18112334. PMC5713303. PMID29113075. More recently, Fuller's laboratory also discovered that sleep can be promoted by the activation of a gamma-aminobutyric acid-ergic (GABAergic) population of neurons located in the parafacial zone [11,12], while the role of the GABAergic A2AR-expressing neurons of the nucleus accumbens [13] and the striatum has just been revealed [14,15].
^Oishi Y, Xu Q, Wang L, Zhang BJ, Takahashi K, Takata Y, Luo YJ, Cherasse Y, Schiffmann SN, de Kerchove d'Exaerde A, Urade Y, Qu WM, Huang ZL, Lazarus M (September 2017). "Slow-wave sleep is controlled by a subset of nucleus accumbens core neurons in mice". Nature Communications. 8 (1): 734. Bibcode:2017NatCo...8..734O. doi:10.1038/s41467-017-00781-4. PMC5622037. PMID28963505. Here, we show that chemogenetic or optogenetic activation of excitatory adenosine A2A receptor-expressing indirect pathway neurons in the core region of the NAc strongly induces slow-wave sleep. Chemogenetic inhibition of the NAc indirect pathway neurons prevents the sleep induction, but does not affect the homoeostatic sleep rebound.
