Cellular Composition of the Preoptic Area Regulating Sleep, Parental, and Sexual Behavior

Abstract

The preoptic area (POA) has long been recognized as a sleep center, first proposed by von Economo. The POA, especially the medial POA (MPOA), is also involved in the regulation of various innate functions such as sexual and parental behaviors. Consistent with its many roles, the MPOA is composed of subregions that are identified by different gene and protein expressions. This review addresses the current understanding of the molecular and cellular architecture of POA neurons in relation to sleep and reproductive behavior. Optogenetic and pharmacogenetic studies have revealed a diverse group of neurons within the POA that exhibit different neural activity patterns depending on vigilance states and whose activity can enhance or suppress wake, non-rapid eye movement (NREM) sleep, or rapid eye movement (REM) sleep. These sleep-regulating neurons are not restricted to the ventrolateral POA (VLPO) region but are widespread in the lateral MPOA and LPOA as well. Neurons expressing galanin also express gonadal steroid receptors and regulate motivational aspects of reproductive behaviors. Moxd1, a novel marker of sexually dimorphic nuclei (SDN), visualizes the SDN of the POA (SDN-POA). The role of the POA in sleep and other innate behaviors has been addressed separately; more integrated observation will be necessary to obtain physiologically relevant insight that penetrates the different dimensions of animal behavior.

The Role of Reproductive Hormones in Sex Differences in Sleep Homeostasis and Arousal Response in Mice

“…Current findings clearly show that there are large sex differences in sleep/wakefulness in mice. Since the rodent brain has sexual dimorphism, which underlies sex differences in innate behaviors such as sexual behavior, aggression, and parental behavior ( Bonthuis et al, 2010 ; McCarthy et al, 2017 ; Tsuneoka et al, 2017a ; Fujiyama et al, 2018 ; Tsuneoka and Funato, 2021 ), it is possible that sleep/wake behaviors are also controlled by neural groups with sexual dimorphism. Although the current study shows the role of gonadal hormone in sleep/wake regulation, gonadectomy does not eliminate all sex differences in sleep.…”

“…In male, testosterone also act on estrogen receptors, as well as androgen receptors, through aromatization to estradiol ( Purves-Tyson et al, 2012 ). Given that the MPOA expresses receptors for reproductive hormones and contains neurons that regulate sleep/wakefulness and exhibit sexual dimorphism ( Liu and Dan, 2019 ; Tsuneoka and Funato, 2021 ), the MPOA may be involved in sex difference in sleep/wakefulness.…”

Sleep promoting neurons remodel their response properties to calibrate sleep drive with environmental demands.

“…Thus, it is possible that additional sleep and wake promoting circuits downstream of AstA-GAL4 or 65D05-GAL4 will be found elsewhere in the brain. It is interesting to note that neurons expressing the mouse homologue of AstA, galanin, also regulate conflicting behaviors [77]. Specifically, Galanin expressing neurons that project to the tuberomammillary nucleus promote sleep while Galanin expressing neurons that projection to the medial amygdala promote parental behaviors [77, 87, 88].…”

“…It is interesting to note that neurons expressing the mouse homologue of AstA, galanin, also regulate conflicting behaviors [77]. Specifically, Galanin expressing neurons that project to the tuberomammillary nucleus promote sleep while Galanin expressing neurons that projection to the medial amygdala promote parental behaviors [77, 87, 88]. Thus it will be important for future studies to discern how AstA and galanin circuits regulate competing activities in other circuits.…”

Nitric Oxide Synthase Neurons in the Preoptic Hypothalamus Are NREM and REM Sleep-Active and Lower Body Temperature

“…The PO area also contains neurons that are required for REM sleep ( Lu et al, 2000 ), including REM-promoting cells in MPO ( Suntsova and Dergacheva, 2004 ; Gvilia et al, 2006 ). The PO area, which contains a huge diversity of cells ( Moffitt et al, 2018 ; Tsuneoka and Funato, 2021 ), also contributes to regulating many other functions, including nesting, thermoregulation, parenting, sexual behavior, water consumption, blood osmolarity, and daily torpor ( Nakamura and Morrison, 2008 , 2010 ; Morrison and Nakamura, 2011 ; Saper and Lowell, 2014 ; Abbott and Saper, 2017 ; Hrvatin et al, 2020 ; Takahashi et al, 2020 ; Tsuneoka and Funato, 2021 ).…”