Clitoral sexual arousal: neuronal tracing study from the clitoris through the spinal tracts.

PURPOSE: Although genital tactile stimulation is regarded as a precursor to sexual arousal and a recognized initiator of central nervous system arousal, specific afferent neural pathways transmit sensory stimuli of arousal, beginning at the epithelial level on the clitoris and following the course of arousal stimuli through the central nervous system. Limited knowledge exists of the pathway from the cutaneous receptors of nerves originating in the epithelial tissue of the clitoris and continuing to spinal cord afferents. Such information may contribute to an understanding of sexual arousal, particularly in female vertebrates. We further defined the neural pathways and mechanisms responsible for arousal originating in the epithelium of the clitoris as well as related neural pathways to the spinal cord in a murine model. MATERIALS AND METHODS: We performed a comprehensive review of the published relevant clinical and histological material from human and nonhuman vertebrate studies. In 29 adult female C57B1/6 mice the distribution of pelvic nerves and vessels was mapped. Gross dissection of 4 female mice was facilitated by resin injection of the vascular system in 2. Neuronal tracing was performed in 25 mice that received clitoral injection of wheat germ agglutinin-horseradish peroxidase into the clitoris and were sacrificed after 72 to 96 hours. The spinal cord and periclitoral tissue were removed and fixed. Immunohistochemistry was performed. RESULTS: Gross anatomy of the mouse clitoris showed that pudendal and hypogastric nerves have a major role in the innervation of the external genitalia. Neuronal tracing revealed that the greatest nerve density was noted in the L5/6 spinal cord. The distribution extended from S1 to L2 with no labeling seen in the L3 spinal cord. Wheat germ agglutinin-horseradish peroxidase labeling was seen caudal in levels S1 through L4 and rostral in L2. CONCLUSIONS: Understanding the neuroanatomy of the clitoris using a murine model may provide a valuable tool for the study of sexual arousal disorders and the further understanding of sexual function related to neural pathologies and trauma.

Clitoral sexual arousal: an immunocytochemical and innervation study of the clitoris.

OBJECTIVE: To further define neural pathways and mechanisms responsible for the arousing properties of the epithelium of the clitoris as well as related neural pathways associated with sexual arousal in a murine model. MATERIALS AND METHODS: Adult female C57B1/6 mice were used for gross dissection, facilitated by resin injection of the vascular system, and silver staining, and immunostaining for S-100 and neuronal nitric oxide synthase (nNOS). We also comprehensively reviewed relevant published clinical and histological material from both human and non-human vertebrate studies. RESULTS: The distal innervation consists of three nerve bundles: one related to the perineal region, one through the corpus cavernosum, and the third between the dorsal part of the clitoris and the urethra. Communicating nerve fibres were identified between the perineal, the corpus cavernous nerve (CN) and the dorsal nerve of the clitoris. Immunostaining for nNOS showed that the CN sends nNOS-positive fibres to join the dorsal nerve of the clitoris. In the same distal area of the clitoris, the connecting branches between the perineal nerve and the dorsal nerve of the clitoris are also nNOS positive. CONCLUSIONS: A rich network of nerve bundles and terminal branches were identified and associated with nNOS immunostaining in the cavernosal tissue of the body of clitoris. NO control of vasodilatation and neuronal signalling between the CN and the dorsal nerve of the clitoris could contribute to the engorgement and subsidence of clitoral tissue. This supports the initiation of sexual arousal by tactile stimuli. The distribution pattern of the general and peptidergic innervation in the murine clitoris is similar to that of the penis.

Interactions between estrogen effects and hunger effects in ovariectomized female mice. I. Measures of arousal.

UNLABELLED: Measures of arousal were used to study effects of estradiol and food restriction, and their potential interactions, in ovariectomized female C57Bl/6 mice. It was hypothesized based on a proposed theoretical equation [Pfaff, D.W., 2006a. Brain Arousal and Information Theory. Harvard University Press, Cambridge, Pfaff, D.W., (Ed.), 2006b. Knobil and Neill's The Physiology of Reproduction, 3rd edition. Elsevier/Academic Press, San Diego] that each treatment would increase arousal-related behaviors and that their combination would further increase arousal behavior. Following baseline testing, animals (n=28) were divided into 3 groups that, in different experimental phases, received either estradiol (in subcutaneous capsules), restricted diet (a liquid diet providing 60% of daily caloric requirements) or a combination of those two. An automated arousal behavior monitoring system was used to measure home cage voluntary motor activity and sensory responsiveness, these being components of a new operational definition of 'generalized arousal'. KEY FINDINGS: (1) During the light, all treatments reduced voluntary activity. (2) In the dark, estrogens increased, while estrogens in combination with restricted diet decreased, horizontal activity. (3) In the dark, restricted diet alone had little effect on voluntary activity, but reduced it when combined with estrogen treatment. (4) All treatments reduced responses to the olfactory stimulus. The dependence of results on time of day was unexpected. Further, different patterns of results for the three treatments suggest that estrogens and food restriction did not have equivalent or additive effects on arousal. While contrary to the main prediction, these findings are discussed in terms of the animals' adaptive preparations for reproduction [Schneider, J.E., 2006. Metabolic and hormonal control of the desire for food and sex: implications for obesity and eating disorders. Horm. Behav. 50, 562-571].

Mouse model of diffuse brain damage following anoxia, evaluated by a new assay of generalized arousal.

Diffuse brain damage following anoxia due to cardiac failure, drowning, carbon monoxide exposure or other accidents constitutes a major medical problem. We have created a novel mouse model using the breathing of pure nitrogen, followed by a recently developed assay that reflects an operational definition of generalized arousal. The operational definition is precise, complete, and leads to quantitative, physical measures in a genetically tractable animal. Exposure to pure nitrogen for controlled periods had a surprising bifurcate effect: about half the mice survived with neurological measures that were virtually normal while the other half died. The new assay detected behavioral deficits unrevealed by neurological screening. Two important features of the results were that (i) deficits were not equal across the circadian cycle, and (ii) deficits were not equal across all the measures within the operational definition of arousal. Specific voluntary motor measurements were decreased in a manner that depended on the phase of the circadian cycle. Sensory responses were also decreased, with an emphasis on vertical movement responses; but, interestingly, fear learning was not damaged. This study establishes the first useful approach to diffuse brain damage in a genetically tractable animal. The model and its outcome measurements will be useful during future attempts at amelioration of acquired neurological disabilities following hypoxic-ischemic injuries.

Mechanisms underlying sexual and affiliative behaviors of mice: relation to generalized CNS arousal.

The field of social neuroscience has grown dramatically in recent years and certain social responses have become amenable to mechanistic investigations. Toward that end, there has been remarkable progress in determining mechanisms for a simple sexual behavior, lordosis behavior. This work has proven that specific hormone-dependent biochemical reactions in specific parts of the mammalian brain regulate a biologically important behavior. On one hand, this sex behavior depends on underlying mechanisms of CNS arousal. On the other hand, it serves as a prototypical social behavior. The same sex hormones and the genes that encode their receptors as are involved in lordosis, also affect social recognition. Here we review evidence for a micronet of genes promoting social recognition in mice and discuss their biological roles.

The effects of mating stimulation on c-Fos immunoreactivity in the female hamster medial amygdala are region and context dependent.

During mating in hamsters, both tactile and nontactile sensory stimulation experienced by the female affect sexual behavior and progestational neuroendocrine reflexes. To test the interactions of these types of mating stimulation, c-Fos immunohistochemistry measured brain cellular activity during sexual behavior under conditions that included combinations of tactile and nontactile mating stimulation. Test groups received: (1) mating stimulation from a male, females being either fully mated or mated while wearing a vaginal mask, or (2) experimenter applied manual vaginocervical stimulation (VCS)-with or without males present, or (3) handling similar to VCS but without insertions-with or without males present. Numbers of c-Fos immunoreactive cells were counted in specific subdivisions of the posterior medial amygdala (MeP) and ventromedial hypothalamus (VMH). The medial amygdala dorsal and ventral subdivisions responded differentially to components of mating stimulation. The posterodorsal Me (MePD) cellular activation was greatest during mating conditions that included VCS and/or males present. However, the posteroventral Me (MePV) was sensitive to male exposure and not to VCS. Also, MePV and VMH shell responses mirrored each other, both being primarily sensitive to male exposure. In separate tests, manual VCS induced pseudopregnancy, though the procedure was most effective with additional nontactile stimulation from males present. In summary, contextual cues provided by nontactile male stimulation enhance the effect of vaginocervical and other tactile stimulation on reproductive processes. Furthermore, c-Fos expression in the female hamster medial amygdala is region and context dependent.