SEG · Anatomical and functional characterization of the neural circuits controlling ejaculation

Anatomical and functional characterization of the neural circuits controlling ejaculation

Despite the importance of sex for the existence and quality of human life, its underlying neurobiological mechanisms are poorly understood. Sex fits the basic structure of pleasure cycles and can be divided into appetitive, consummatory and inhibitory phases. This proposal focuses on the consummatory (ejaculation) phase in mice. During sexual behaviour, copulation-related sensory information and modulatory signals from the brain must be integrated and converted into the motor and secretory outputs that characterize ejaculation. Studies in humans and rats suggest the existence of a group of interneurons in the lumbar spinal cord that mediates this step: the spinal ejaculation generator (SEG). The SEG is thought to control motor neuron activity innervating the bulbospongiosus muscle (BSM): the BSM surrounds the base of the penis, and its rhythmic contraction is necessary for ejaculation to occur. The SEG has access to peripheral information via the sensory branch of the pudendal nerve and descending input from the brain. Experiments in the rat suggest that the SEG can trigger ejaculation and might also be involved in the establishment of the post-ejaculatory refractory period (PERP), during which male mice won’t perform any sexual behaviour. However, these ideas remain controversial, in part because the methods used have poor anatomical and cellular specificity and low temporal resolution. Hence, we employed cutting-edge molecular based strategies with high specificity (viruses combined with transgenic mice) and high temporal resolution (optogenetics and electrophysiology) to gain mechanistic insights about the neural circuits controlling ejaculation. Thereby, we found that BSM-motor neurons receive direct synaptic input from a group of galanin-expressing (Gal+) interneurons located in the upper lumbar spinal cord and that this population is progressively activated during sexual behavior and the recipient of genital sensory input. Electrical and optogenetic activation of the Gal+ neurons evoked BSM-motor neuron and BSM-muscle activity after spinalization, but the effects were dependent on the behavioral state of the male and drastically decreased with repeated stimulation. Moreover, genetic ablation of the Gal+ neurons severely impacted the latency to ejaculate and the structure of the copulatory sequence. Taken together, our results imply an unexpected involvement of the spinal cord in the integration of signals during copulation and in the post-ejaculatory refractory period, suggesting a more central and intricate involvement of the periphery in the control of copulatory behavior than previously suspected.

Data: CORDIS, © European Union