Erectile Function and Sexual Behavior: A Review of the Role of Nitric Oxide in the Central Nervous System

Nitric oxide (NO), the neuromodulator/neurotransmitter formed from l-arginine by neuronal, endothelial and inducible NO synthases, is involved in numerous functions across the body, from the control of arterial blood pressure to penile erection, and at central level from energy homeostasis regulation to memory, learning and sexual behavior. The aim of this work is to review earlier studies showing that NO plays a role in erectile function and sexual behavior in the hypothalamus and its paraventricular nucleus and the medial preoptic area, and integrate these findings with those of recent studies on this matter. This revisitation shows that NO influences erectile function and sexual behavior in males and females by acting not only in the paraventricular nucleus and medial preoptic area but also in extrahypothalamic brain areas, often with different mechanisms. Most importantly, since these areas are strictly interconnected with the paraventricular nucleus and medial preoptic area, send to and receive neural projections from the spinal cord, in which sexual communication between brain and genital apparatus takes place, this review reveals that central NO participates in concert with neurotransmitters/neuropeptides to a neural circuit controlling both the consummatory (penile erection, copulation, lordosis) and appetitive components (sexual motivation, arousal, reward) of sexual behavior.

Pubertal sex hormones control transcriptional trajectories in the medial preoptic area

Pubertal maturation aids development of emotion, cognition, and reproduction. We investigated transcriptional dynamics in the medial preoptic area (MPOA), a hypothalamic center for reproductive behaviors, in male and female mice at single-cell resolution (scRNAseq) during puberty. Defined subsets of neurons expressing Slc32a1 and Esr1 (Vgat+ Esr1+) were the most transcriptionally dynamic compared to other cell types throughout puberty. These cell type specific transcriptional progressions towards adulthood were bidirectionally controlled by the levels of circulating testosterone and estradiol. Selective deletion of Esr1 in Slc32a1-expressing cells in the MPOA prior to puberty arrested transcriptional progression and revealed a sexually dimorphic gene-regulatory network governed by Esr1. Deletion of Esr1 in Vgat+ cells prevented the development of mating behavior in both sexes. These analyses reveal both sexually common and dimorphic transcriptional progressions during puberty as well as their regulatory mechanisms, which have important implications towards understanding adaptative and maladaptive processes governing adolescent brain development.

Role of hypocretin in the medial preoptic area in the regulation of sleep, maternal behavior and body temperature of lactating rats.

The hypocretins (HCRT), also known as orexin, includes two neuroexcitatory peptides, HCRT-1 and HCRT-2 (orexin A y B, respectively), synthesized by neurons located in the postero-lateral hypothalamus, whose projections and receptors are widely distributed throughout the brain, including the medial preoptic area (mPOA). HCRT have been associated with a wide range of physiological functions including sleep-wake cycle, maternal behavior and body temperature, all regulated by the mPOA. Previously we showed that HCRT in the mPOA facilitates certain active maternal behaviors, while the blockade of HCRT-R1 increased the time spent in nursing. As mother rats mainly sleep while they nurse, we hypothesize that HCRT in the mPOA of lactating rats reduce sleep and nursing, while the intra-mPOA administration of the dual orexin receptor antagonist (DORA) would generate the opposite effect. Therefore, the aim of this study was to determine the role of HCRT within the mPOA, in the regulation and integration of the sleep-wake cycle, maternal behavior and body temperature of lactating rats. To evaluate this idea, we assessed the sleep-wake states, maternal behavior and body temperature of lactating rats following microinjections of HCRT-1 (100 and 200 uM) and DORA (5mM) into the mPOA. As expected, our data shows that HCRT-1 in mPOA promoted wakefulness and a slightly increase in body temperature, whereas DORA increased both NREM and REM sleep along with nursing and milk ejection. Taken together, our results strongly suggest that the reduction of the endogenous HCRT within the mPOA of lactating rats is important to promote sleep, nursing and milk ejection.

A Scientometric Approach to Review the Role of the Medial Preoptic Area (MPOA) in Parental Behavior

Research investigating the neural substrates underpinning parental behaviour has recently gained momentum. Particularly, the hypothalamic medial preoptic area (MPOA) has been identified as a crucial region for parenting. The current study conducted a scientometric analysis of publications from 01 January 1972 to 19 January 2021 using CiteSpace software to determine trends in the scientific literature exploring the relationship between MPOA and parental behaviour. In total, 677 scientific papers were analysed, producing a network of 1509 nodes and 5498 links. Four major clusters were identified: "C-Fos Expression'', "Lactating Rat'', "Medial Preoptic Area Interaction'' and "Parental Behavior''. Their content suggests an initial trend in which the properties of the MPOA in response to parental behavior were studied, followed by a growing attention towards the presence of a brain network, including the reward circuits, regulating such behavior. Furthermore, while attention was initially directed uniquely to maternal behavior, it has recently been extended to the understanding of paternal behaviors as well. Finally, although the majority of the studies were conducted on rodents, recent publications broaden the implications of previous documents to human parental behavior, giving insight into the mechanisms underlying postpartum depression. Potential directions in future works were also discussed.

A Scientometric Approach to Review the Role of the Medial Preoptic Area (MPOA) in Parental Behavior

Research investigating the neural substrates underpinning parental behaviour has recently gained momentum. Particularly, the hypothalamic medial preoptic area (MPOA) has been identified as a crucial region for parenting. The current study conducted a scientometric analysis of publications from 1 January 1972 to 19 January 2021 using CiteSpace software to determine trends in the scientific literature exploring the relationship between MPOA and parental behaviour. In total, 677 scientific papers were analysed, producing a network of 1509 nodes and 5498 links. Four major clusters were identified: “C-Fos Expression”, “Lactating Rat”, “Medial Preoptic Area Interaction” and “Parental Behavior”. Their content suggests an initial trend in which the properties of the MPOA in response to parental behavior were studied, followed by a growing attention towards the presence of a brain network, including the reward circuits, regulating such behavior. Furthermore, while attention was initially directed uniquely to maternal behavior, it has recently been extended to the understanding of paternal behaviors as well. Finally, although the majority of the studies were conducted on rodents, recent publications broaden the implications of previous documents to human parental behavior, giving insight into the mechanisms underlying postpartum depression. Potential directions in future works were also discussed.

A Scientometric Approach to Review the Role of the Medial Preoptic Area (MPOA) in Parental Behavior

Research investigating the neural substrates underpinning parental behaviour has recently gained momentum. Particularly, the hypothalamic medial preoptic area (MPOA) has been identified as a crucial region for parenting and other parent-related behaviour. The current study conducted a scientometric analysis of publications from 01 January 1972 to 19 January 2021 using CiteSpace software to determine trends in the scientific literature exploring the relationship between MPOA and parental behaviour. 677 scientific papers were analysed, producing a network of 1,509 nodes and 5,498 links. Four major clusters were identified: ``C-Fos Expression", ``Lactating Rat", ``Medial Preoptic Area Interaction" and ``Parental Behavior". Their content suggests an initial trend in which the properties of the MPOA in response to parental behavior were studied, followed by a growing attention towards the presence of a brain network, including the reward circuits, regulating such behavior. Furthermore, while attention was initially directed uniquely to maternal behavior, it has recently been extended to the understanding of paternal behaviors as well. Finally, although the majority of the studies were conducted on rodents, recent publications broaden the implications of previous documents to human parental behavior, giving insight into the mechanisms underlying postpartum depression. Potential directions in future works were also discussed.