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Michigan State UniversityBreedlove Jordan lab at MSU

Spinal Nucleus of the Bulbocavernosus

SNB Figure 1. SNB motoneurons are more numerous in male than in female rats

In rats, the motoneurons of the spinal nucleus of the bulbocavernosus (SNB) innervate striated muscles (bulbocavernosus and levator ani) attached to the base of the penis. Before birth, male and female rats have the muscles and the SNB motoneurons innervating them, but both die in females in the first week of life. The SNB system survives in males because they secrete androgenic hormones such as testosterone to spare the system from cell death. Thus in adulthood there is a prominent sexual dimorphism in the SNB region of the spinal cord (Figure 1). So if you expose newborn female rats to testosterone, you prevent the death of the motoneurons and their targets for life. We have evidence that the SNB motoneurons are not directly responding to the androgen. By elimination, it seems likely that androgen acts upon the target muscles to keep them alive and that the muscles in turn keep the SNB motoneurons alive. We would like to confirm this idea that the muscles are the primary site of androgen action to spare the SNB system, and ask which particular cell population within the muscles (muscle fibers, fibroblasts, Schwann cells, endothelial cells) are responding to the hormone.

SNB Figure 2. Androgen stimulation of target muscles augments dendrites in 2 or the 3 fields

In adulthood, the SNB system continues to respond to androgen. Castrating adult male rats causes the somata and dendrites of SNB motoneurons to shrink. Treating castrates with androgen can prevent or reverse this effect. Androgen acts directly on the muscle fibers to cause them to enlarge, too. The effect of androgen on SNB motoneuron somata is a direct, cell-autonomous response, as only SNB motoneurons that make functional androgen receptors can expand their somata after androgen treatment. On the other hand, androgen acts indirectly to expand SNB motoneuronal dendrites, because androgen treatment at the muscle can cause the dendrites to expand (Figure 2). We would like to know how the target muscles direct their innervating SNB motoneurons to expand dendrites and make new synapses.

SNB Figure 3. MK-801 blocks androgen's effect on SNB motoneuron size

NMDA-type glutamate receptors play a role in the androgen-responsiveness of adult SNB motoneurons. Pharmacological blockade of NMDA receptors prevents the motoneurons from expanding their somata in response to adult androgen treatment (Figure 3). We would like to identify the neurons that are providing glutamate stimulation to SNB motoneurons and ask how they contribute to androgen-mediated neural plasticity in this system.