Activation of the Ventrolateral Preoptic Neurons Projecting to the Perifornical-Hypothalamic Area Promotes Sleep: DREADD Activation in Wild-Type Rats

Abstract

The ventrolateral preoptic area (VLPO) predominantly contains sleep-active neurons and is involved in sleep regulation. The perifornical-hypothalamic area (PF-HA) is a wake-regulatory region and predominantly contains wake-active neurons. VLPO GABAergic/galaninergic neurons project to the PF-HA. Previously, the specific contribution of VLPO neurons projecting to the PF-HA (VLPO > PF-HAPRJ) in sleep regulation in rats could not be investigated due to the lack of tools that could selectively target these neurons. We determined the contribution of VLPO > PF-HAPRJ neurons in sleep regulation by selectively activating them using designer receptors exclusively activated by designer drugs (DREADDs) in wild-type Fischer-344 rats. We used a combination of two viral vectors to retrogradely deliver the Cre-recombinase gene, specifically, in VLPO > PF-HA neurons, and further express hM3Dq in those neurons to selectively activate them for delineating their specific contributions to sleep–wake functions. Compared to the control, in DREADD rats, clozapine-N-oxide (CNO) significantly increased fos-expression, a marker of neuronal activation, in VLPO > PF-HAPRJ neurons (2% vs. 20%, p p p PF-HAPRJ neurons constitute a critical component of the hypothalamic sleep–wake regulatory circuitry and promote sleep by suppressing wake-active PF-HA neurons.

Keywords

• sleep
• hypothalamus
• ventrolateral preoptic area
• designer receptors exclusively activated by designer drugs
• clozapine-N-oxide
• Fischer-344 rats