Central regulation of ejaculation
Introduction
Male sexual behavior is a motivated behavior dependent on intrinsic and extrinsic signals [55]. It is a complex behavior consisting of several components, including pursuit and investigation of the female, mounting and intromissions, the culmination of which, results in ejaculation. Ejaculation is defined as the expulsion of seminal fluid from the urethral meatus [86], [96]. In men, ejaculation is closely associated with orgasm, which refers to the ejaculation, extragenital responses and the subjective pleasurable feelings. Analogously, rats ejaculation is associated with reward [119]. Ejaculation is mediated by a spinal control center, referred to as a spinal ejaculation generator [86], [96], spinal pattern generator [98], spinal pacemaker [126] or central pattern generator [18]. This spinal ejaculation generator coordinates sympathetic, parasympathetic and motor outflow to induce the two phases of ejaculation, emission and expulsion. In addition, the spinal ejaculation generator integrates this outflow with inputs related to the summation of sexual activity prior to ejaculation and that are required to trigger ejaculation. In turn, the spinal ejaculation generator is under the influence of supraspinal sites in brainstem, hypothalamus and preoptic area. Finally, sensory information related to ejaculation is processed in the spinal cord and brain, possibly contributing to the rewarding properties of ejaculation. This is summarized in Fig. 1.
The purpose of this paper is to review the current knowledge of the central pathways involved in regulation of the multiple aspects of ejaculation. The review will primarily focus on studies performed in rat, unless noted otherwise. The spinal efferents and innervation of the pelvic organs will first be discussed, followed by a review of the spinal afferents that relay sensory information involved in triggering ejaculation. Subsequently, new evidence concerning the spinal ejaculation generator is summarized. Finally, supraspinal sites involved in descending control of the spinal reflexes or receiving ascending inputs related to ejaculation are reviewed.
Section snippets
Evidence for a spinal ejaculation generator
Ejaculation is a spinal reflex, best illustrated by the ability of vibratory stimulation of the penis to induce ejaculation in patients with complete spinal cord transection above the 10th thoracic segmental level [13], [14], [40], [132]. Likewise, in animals, ejaculatory reflexes remain intact upon transection of the spinal cord [98], [116]. The ability of a peripheral stimulation to induce ejaculation despite the complete loss of reciprocal connections with supraspinal structures implies that
Autonomic nuclei
Ejaculation consists of two phases: emission and expulsion. Emission involves parasympathetic responses, such as secretion of seminal fluids from epithelial cells and the accessory sex glands, as well as sympathetic responses that move the seminal fluids to the proximal urethra. The latter includes contraction of the ductus deferens, and closure of the bladder neck. Expulsion of the semen, which involves both sympathetic and somatic outputs, is a result of rhythmic contractions of striated
Motor nuclei
Somatic motor outputs are also involved in the ejaculatory reflex, specifically the pudendal motoneurons, which are located in the lumbosacral spinal cord (Fig. 2). In humans, cats and primates, the pudendal motoneurons are located in a single nucleus called Onuf's nucleus [79], [129], [136]. In the rat, this nucleus consists of a medial (DM, also referred to as the spinal nucleus of the bulbocavernosus, SNB) and a lateral (DL) group of motoneurons innervating the striated perineal muscles,
Sensory inputs trigger ejaculation
The onset of ejaculation is triggered by sensory inputs to the spinal ejaculation generator during the sexual activity prior to ejaculation. The precise nature of the afferent stimuli that activate the spinal ejaculation generator and thus trigger ejaculation is unknown and may involve somatosensory, visceral sensory, or proprioceptive inputs. Somatosensory inputs may derive from tactile stimulation of the penis. The penis has a high density of sensory fibers, but tactile sensitivity (light
Spinal afferents
The majority of the spinal afferents involved in transmitting the sensory inputs mediating ejaculation travel via the pudendal nerve and the dorsal nerve of the penis (DNP), a branch of the pudendal nerve (Fig. 2). Pudendal nerve fibers terminate primarily in the lower lumbar and upper sacral segments, bilaterally, in the medial portions of the dorsal horn and the dorsal gray commissure [97], [123], [141]. In addition, there is a less prominent projection to the lateral edge of the dorsal horn
Interneurons
An integral component of a spinal ejaculation generator is a group of interneurons in the lumbosacral spinal cord that convert sensory signals into motor and/or secretory outputs [96]. The exact location and identity of these interneurons has long been unknown. Previous studies have used viral tract tracing from pelvic organs to identify interneurons that are presynaptic to pudendal motor neurons and autonomic preganglionic neurons [90], [92], [134]. These interneurons are located bilaterally
Supraspinal control: descending pathways
So far, we have discussed the spinal control of ejaculation by the spinal ejaculation generator. It is important to note that this spinal control center is in turn under descending inhibitory and excitatory influence of supraspinal sites [90], [95]. These sites include the medial preoptic area (MPOA) [58], [87], [115], paraventricular nucleus of the hypothalamus (PVN) [91] and the nucleus paragigantocellularis (nPGi) [88], [89], [103], [156]. These sites form a heavily interconnected network
Relay of sensory signals related to ejaculation
The neural pathways for relay of ejaculation-related sensory information to the brain are currently unclear. Recently, our laboratory identified one candidate pathway in the position to relay ejaculation-related signals from the pelvic organs to the thalamus via the lumbar spinal cord. Specifically, the LSt cells previously discussed for their role in triggering ejaculation form a nodal point in this spinothalamic pathway. LSt cells provide inputs to a medial subdivisions of the SPFp [26], [65]
Ejaculation, reward and learning
In male rodents, sexual behavior is a rewarding behavior, and ejaculation appears to be the most reinforcing component of sexual behavior (for a review, see Ref. [119]). In contrast to males allowed to intromit or mount, but not ejaculate, males allowed to copulate to ejaculation developed faster running speeds in T-mazes [66], straight-arm runway [82], or hurdle climbing [130]. In addition, Kippin and Pfaus [72] demonstrated that ejaculation was essential for the formation of conditioned
Conclusion
Great progress has been made in recent years towards a better understanding of the central regulation of ejaculatory function. However, major gaps in our knowledge remain, including the sensory signals and pathways that trigger ejaculation; the mechanisms via which LSt cells control ejaculation; the supraspinal circuitry that influences the spinal ejaculation generator; the ascending anatomical pathways that relay sensory signals related to ejaculation to the brain; and finally, the neural
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