Sleep‐active neurons in the preoptic area project to the hypothalamic paraventricular nucleus and perifornical lateral hypothalamus

Abstract

The lamina terminalis consists of the organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus (MnPO) and subfornical organ. The MnPO and ventrolateral preoptic area (vlPOA) are known to contain high densities of neurons that are sleep active. The prevalence of sleep-active neurons in the OVLT and subfornical organ is unknown. The vlPOA and subdivisions of the lamina terminalis project to hypothalamic regions involved in the control of behavioral, electrographic or autonomic arousal, including the lateral hypothalamic area (LHA) and paraventricular nucleus (PVN). The extent to which projection neurons are active during sleep is unknown. We quantified c-Fos protein immunoreactivity (IR) in the lamina terminalis and vlPOA in sleeping and awake rats that received injections of retrograde tracer into either the LHA or PVN. Fos IR was also examined in lamina terminalis neurons following tracer injections into the vlPOA. Significantly more projection neurons from the MnPO, OVLT and vlPOA to the LHA were Fos-immunoreactive in sleeping vs. awake animals. Waking Fos IR was more prevalent in lamina terminalis neurons projecting to the PVN although a subset of MnPO projection neurons in sleeping rats was Fos-immunoreactive. Almost 50% of vlPOA-PVN projection neurons expressed Fos IR during sleep, compared with 3% during waking. Significantly more neurons in the OVLT and MnPO projecting to the vlPOA were Fos-immunoreactive in sleeping vs. awake rats. Inhibition of LHA and PVN neurons arising from OVLT, MnPO and vlPOA neurons may contribute to suppression of behavioral, electroencephalographic and sympathetic nervous system activation during sleep.

The Median Preoptic Nucleus Reciprocally Modulates Activity of Arousal-Related and Sleep-Related Neurons in the Perifornical Lateral Hypothalamus

“…Recent anatomical studies showed that the MnPN input to the PF/LH is one of the heaviest among the structures involved in control of behavioral states (Yoshida et al, 2006). MnPN-PF/LH projection neurons include a subset of cells exhibiting sleep-related c-Fos immunoreactivity (Uschakov et al, 2006). These findings allow us to hypothesize that MnPN plays an important role in sleeprelated inhibitory modulation of hypocretin and nonhypocretin arousal-related PF/LH neurons.…”

“…If these projections originate in sleep-related cells, they are expected to be excitatory. Activation of GABA/galaninergic VLPO neurons projecting to the PF/LH Uschakov et al, 2006;Yoshida et al, 2006) is likely to be a complementary mechanism of inhibitory control of PF/LH arousal network.…”

“…Here, we show that MnPN inactivation results in sustained wakefulness. Many MnPN sleep-active neurons are GABAergic and project to different neuronal groups involved in arousal control, including the PF/LH (Uschakov et al, 2006), one of the key components of the wake-promoting system. Our data indicate that majority of PF/LH wake-active neurons receive inhibitory inputs from the MnPN.…”

Orexins and the cardiovascular events of awakening

“…A set of testable hypotheses has been recently proposed. 4 The lower values of SNA to the skeletal muscles and kidneys during NREM sleep compared with wakefulness may result from: (a) inhibition of a "stress pathway" that involves the hypothalamic paraventricular nucleus, 21 a master autonomic and endocrine controller; 22 (b) inhibition of a "command neuron" pathway that involves the pedunculopontine nucleus of the rostral pons, 23,24 part of the mesencephalic locomotor region; 25 and (c) potentiation of a "baroreflex pathway" 26 that involves the pontine parabrachial nucleus 27 and the medullary nucleus of the solitary tract. 28 The lower values of skin SNA during NREM sleep compared with wakefulness may result from inhibition of a "thermoregulatory pathway" for heat generation and retention, which includes the hypothalamic median preoptic nucleus, the hypothalamic medial preoptic area, and the rostral medullary raphe.…”

Neurobiology of Arousal and Sleep: Updates and Insights Into Neurological Disorders

“…MnPO neurons project to the DRN and LC. MnPO and VLPO neurons that express sleep-related c-Fos project to the HCT neuronal field in the lateral hypothalamus [64]. Sleep-active neurons in VLPO and MnPO exhibit discharge profiles across the wake-NREM-REM cycle that are reciprocal to those of wakepromoting HA, 5HT, NE, and HCT neurons [63] .…”