Serotonin differentially modulates excitatory and inhibitory synaptic inputs to putative sleep-promoting neurons of the ventrolateral preoptic nucleus

Abstract

The role of serotonin (5-HT) in sleep-wake regulation has been a subject of intense debate and remains incompletely understood. In the ventrolateral preoptic nucleus (VLPO), the main structure that triggers non-rapid eye movement (NREM) sleep, putative sleep-promoting (PSP) neurons were shown ex vivo to be either inhibited (Type-1) or excited (Type-2) by 5-HT application. To determine the complex action of this neurotransmitter on PSP neurons, we recorded spontaneous and miniature excitatory and inhibitory postsynaptic currents (sEPSCs, sIPSCs, mEPSCs and mIPSCs) in response to bath application of 5-HT. We established in mouse acute VLPO slices that 5-HT reduces spontaneous and miniature EPSC and IPSC frequencies to Type-1 neurons, whereas 5-HT selectively increases sIPSC and mIPSC frequencies to Type-2 VLPO neurons. We further determined that Type-1 neurons display a lower action potential threshold and a smaller soma size than Type-2 neurons. Finally, single-cell RT-PCR designed to identify the 13 serotonergic receptor subtypes revealed the specific mRNA expression of the 5-HT1A,B,D,F receptors by Type-1 neurons. Furthermore, the 5-HT2A-C,4,7 receptors were found to be equivalently expressed by both neuronal types. Altogether, our results establish that the excitatory and inhibitory inputs to Type-1 and Type-2 VLPO PSP neurons are differentially regulated by 5-HT. Electrophysiological, morphological and molecular differences were also identified between these two neuronal types. Our results provide new insights regarding the orchestration of sleep regulation by 5-HT release, and strongly suggest that Type-2 neurons could play a permissive role, whereas Type-1 neurons could have an executive role in sleep induction and maintenance.

Sedative Effect ofSophora flavescensand Matrine

“…Input to type 2 neurons containing 5-HT 2, 4, 7 receptors, however, is enhanced by 5-HT. Although 2 neurons are inversely influenced by 5-TH, they promotes sleep by involving initiation and maintenance of sleep, respectively (Sangare et al ., 2016). It was also reported that injection of 5-HT receptor 1A agonist increases wake time (Monti and Jantos, 2003).…”

TBI and Sleep–Wake Disorders: Pathophysiology, Clinical Management, and Moving towards the Future

“…Sangare et al used whole-cell patch clamp and single-cell reverse tran-scription polymerase chain reaction to identify the likely players in serotonin-mediated wake-and sleep-state transitioning. 25 Their data revealed that in the VLPO nucleus, type 1 neurons uniquely express 5-HT1A receptors, which mediate the inhibitory response to serotonin, while type 2 neurons express primarily 5-HT2C receptors. Taken in conjunction with early human and animal data, 26,27 5-HT2C agonists may therefore be of great value to the selective pharmacological induction of physiological sleep.…”

Neuropeptide S promotes wakefulness through the inhibition of sleep-promoting ventrolateral preoptic nucleus neurons

“…Animals were decapitated at ZT-0. Brains were quickly extracted without removing the meninges, and coronal slices (300 µm thick) were cut as previously described 23,24 . Individual slices were then placed in a submerged recording chamber Vascular reactivity.…”

“…Indeed, the pipette solution contained a low concentration of Cl -(1 mM), resulting in an ECl of -111 mV. Therefore, inward currents were considered as sEPSCs and outward currents as sIPSCs 24 . Data were filtered at 2 kHz, digitized at 10 kHz and acquired on-line using the pCLAMP 10 (Clampex) software (Axon Instruments).…”