The cortex receives sensory information from the penis and genitalia. Stimulation of thalamic and cortical areas associated with somatomotor pathways elicits sexual feelings and genital sensations but does not lead to penile erection. Conversely, stimulation of cortical-subcortical areas linked to the limbic system elicit penile erections in response to stimulation, as demonstrated in monkeys (5,171-173). Direct study of the human brain is limited to observations made during neurosurgical procedures. Conversely, stimulation of the amygdala (a limbic structure) can induce erotic emotions similar to those experienced during intercourse. Analogous observations have been made by comparing the experiences of patients suffering from epilepsy with parietal lobe foci to those with mediobasal temporal foci. Animal experiments have shown that damage to the fornix and prefornical area also injures the paraventricular nucleus (PVN) outflow to the MFB, possibly accounting for the impotence associated with these operations.
The current hypothesis of the inhibitory role of the cortex is supported by the findings of hypersexuality and penile erection in the Kluver-Bucy syndrome, resulting from a lesion in the pyriform cortex and amygdaloid complex. The nucleus para gigantocellu-laris (nPGi) of the brain stem has also been studied for its role in the coordination of erectile control. This region is consistently transneuronally labeled in experiments in which the rat penis is injected with pseudorabies virus (174,175). The nPGi inhibits ejac-ulatory reflexes, and lesions within this nucleus facilitate copulatory reflexes and male sexual behavior (176). In addition to receiving inputs from the medial pre-optic area (MPOA) and PVN, the nPGi also receives dense projections from the midbrain central gray region (177-180). This region has been demonstrated as an important component in the control of sexual function, and the nPGi likely acts as a relay point for forebrain inputs as they descend to the spinal cord.
The limbic system has been described inconsistently over recent decades, but there is a general consensus that it includes cortical and subcortical structures. The amygdala, septal nuclei, fornix, thalamus, hypothalamus, and hippocampus are specifically interesting. These structures influence affect, emotional displays, and male sexual behavior (6,181-187). Cortical signals pass through these limbic structures en route to spinal cord targets, thereby adding an additional level of control to penile erections. Invasive studies in animals have revealed that penile erections may be induced by stimulation of the septal nuclei, mammillary bodies, and other elements ofthe hypothalamus (5,173). Anecdotal reports from human studies using implanted electrodes have indicated that penile erection may occur in response to stimulation of the MFB or septal region. Thalamic loci induce an ejaculatory response that has been shown to occur independently of erection (188). In neurologically intact men, ejaculation is presumed to involve afferent signals evoked by genital stimulation inputs that reach the thalamus.
Numerous experiments have shown that the MPOA ofthe hypothalamus is a key component in the central control ofcopulatory behavior in male mammals (189-194). Neuro-toxin-selective destruction of nerve cell bodies within the MPOA disrupts the male animal's copulatory behavior pattern—that is, mounting and thrusting (195-198)—whereas stimulation of the MPOA facilitates male sexual behavior (189,191,192,199). In rats, stimulation of neurons within the MPOA produces rhythmic firing of the perineal muscles in anesthetized animals as well as a rise in intracavernosal pressure (199). The MPOA contains a high density of testosterone receptors (200) and has numerous interconnec-
tions with other brain regions, including the limbic system, midbrain, and lower autonomic brain stem nuclei (177,201-205). Therefore, the MPOA is capable of integrating sensory and hormonal signals that initiate sexual reflexes in males. Neuro-anatomical tracing studies have demonstrated that axons exiting the MPOA pass through or terminate in many areas ofthe brain, including the MFB. Bilateral lesions of the MFB abolish male sexual behavior. Electrical stimulation as well as micro-injection of excitatory amino acids within the MPOA induce rhythmic firing of pudendal motor neurons. Moreover, in conjunction with contralateral MFB lesions, unilateral electrolytic lesions of the MPOA abolish male sexual behavior. This finding of "asymmetrical" damage disrupting male copulatory behavior to the same extent as bilateral lesions to either the MPOA or MFB is consistent with the concept that both of these structures are components of the pathway that regulates male sexual behavior (176,178-180,205). Recent studies have further shown that lesions within the peri-aqueductal gray region block MPOA-induced activation of the ejaculatory response, indicating that these descending pathways pass through, and likely relay within, the peri-aqueductal gray region (206).
Over several recent decades, several groups have contributed to the initial discovery and further characterization ofthe PVN ofthe hypothalamus as a sexual response center (207-212). The discovery of a group of oxytocinergic neurons within the PVN was particularly important. In response to sexual stimulation, there is an increase in plasma oxytocin levels, with maximum levels reached at the time of ejaculation. Therefore, oxytocin in the circulation plays a facilitative role in penile erections and male sexual behavior. These oxytocinergic neurons are activated by dopamine, excitatory amino acids (i.e., glutamate), and by oxytocin itself via the NOS pathway (213,214). Dopamine receptor agonists, such as the mixed D1/D2 agonist apomorphine, induce penile erection when injected into the PVN (210,215). These neurons are inhibited by y-aminobutyric acid (GABA) and opiates that impair erectile function and copulatory behavior. The oxytocinergic fibers run the length of the entire spinal cord, with connections to both sympathetic and parasympathetic targets. These interconnections may account for another aspect ofthe PVN's role in integrating the neural inputs and outputs that underlie the male sexual response.
The hippocampus appears to act in concert with the PVN in the central neural regulation ofpenile erection. MacLean and Ploog (207) found electroencephalographic evidence of an interaction between the hippocampus and its projections to the septum, the MPOA, and thalamus (via the fornix) during experimentally induced erection. Tumescence was frequently associated with after-discharge in the hippocampus, although other areas of the midbrain had been subjected to electrostimulation. During this recorded hippocam-pal activity, the erections became throbbing in character and reached their maximal size, often waxing and waning in size after discharge for up to 10 min. When certain diencephalic sites were electrostimulated (e.g., the anterior thalamus), erection followed the termination of stimulation rather than occurring with the stimulation. These "rebound" erections were concurrent with hippocampal discharges and provide evidence of the intimate anatomical and functional organization of the inhibitory and excitatory mechanisms involved. Recent investigations have further demonstrated that micro-injection of glutamate receptor agonists within the CA3 hippocampal region leads to a significant increase in intracavernous pressure in rats, similarly to those occurring after activation of the PVN (216-218).
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