Figure 5

Computer model of PMC-PAG switching circuits. Diagram illustrating the putative pathways in the PAG and PMC that contribute to urine storage and voiding. This circuitry shows the neuronal elements and connections used in the computer model. The right side illustrates the ascending afferent limb of the spinobulbospinal micturition reflex that projects to the PAG, and the left side shows the descending limb that connects the PMC direct neuron to the bladder efferent neuron in the sacral spinal cord. During urine storage, as the bladder slowly fills, a low level of afferent activity activates an excitatory neuron (E) in the PAG, which relays information (pathway A) to an inverse neuron (I) in the PMC that in turn provides inhibitory input to the type 1 direct neuron (D) to maintain continence. Bladder afferent input is also received by a second neuron in the PAG (E) that is on the excitatory pathway (pathway B) to the PMC type 1 direct neuron (D) and to a transiently active PMC neuron (T) that fires at the beginning of micturition. However, the PAG excitatory relay neuron (E) is not activated during the early stages of bladder filling because it is inhibited by a tonically active independent neuron (I). The PMC type 1 direct neuron is also inhibited by a tonically active independent neuron (I) located in the PMC. Bladder afferent firing gradually increases during bladder filling, which increases feed-forward inhibition of the direct neuron via the PAG-PMC inverse neuron pathway. However, at a critical level of afferent firing, excitatory input to the PAG excitatory relay neuron surpasses the tonic inhibition and sends signals to the PMC transient neuron. This process briefly inhibits the inverse neuron, reducing inhibitory input to the direct neuron, allowing it to overcome tonic inhibition and fire action potentials that activate by an axon collateral (pathway C), a reciprocal inhibitory neuron (R) that suppresses the inverse neuron (I) and further reduces inhibition of the direct neuron (D). The direct neuron then switches into maximal firing mode and sends excitatory input to the spinal efferent pathway to the bladder, inducing a large bladder contraction and more afferent firing, which further enhances synaptic transmission in the PAG-PMC micturition reflex pathways. The reflex circuitry returns to storage mode as the bladder empties and afferent firing declines. Excitatory neurons are green and inhibitory neurons are red. Reprinted with permission from (31): de Groat WC, Wickens C. (2013) Organization of the neural switching circuitry underlying reflex micturition. Acta Physiol. (Oxf). 207:66–84.