Grant: Discovery Grants Program - Individual

Intercellular communication channels composed of connexin proteins form gap junctions between neurons, creating electrical synapses that mediate direct electrical neurotransmission. My group and others have found electrical synapses formed by connexin36 (Cx36) in many regions of brain and spinal cord. One of our long-term objectives is to extend knowledge of the functional roles of these synapses in neuronal circuitry. Here, we aim to acquire understanding of the requirements for electrical synapses in a neuronal system that governs fundamentally important physiological processes related to sexual behaviour. We have documented an abundance of electrical synapses connecting motoneurons at lower levels of the spinal cord. These motoneurons are unique because, unlike other motoneurons, they are linked by gap junctions and they are sexually dimorphic, meaning that they along with their target muscles are well developed in males and less so in females. These motoneurons control the activity of muscles in the pelvic floor that govern sexual behavior. Intermingled among these motoneurons are those that mediate contraction of the external urethral and external anal sphincters and that also appear to be linked by gap junctions. As in rodents, gap junctions between these motoneurons were found in humans. During elicitation of the urethrogenital reflex, which mimics motoneuronal activity during sexual activity, the dimorphic motoneurons and their target muscles are highly synchronously active. Such synchronization is a hallmark property conferred by electrical synapses. However, electrical coupling between sexually dimorphic motoneurons has not been studied, and nothing is known about how this coupling between these motoneurons innervating their different target muscles might be organized. This dimorphic system provides an ideal model in which the key features that electrical synapses confer in a neuronal network can be related to physiological functions subserved by that network. We hypothesize that electrical coupling is an essential element of dimorphic motoneurons and those innervating sphincter muscles, and is required for coordinating synchronous motoneuronal and target muscle activity during sexual behavior. We will use anatomical and electrophysiological approaches in normal and transgenic mice lacking Cx36 to establish the extent to which these synapses contribute to physiological processes related to sexual activity.