Friday, April 26, 2024
4/26/2024
Abstract The circuit that controls the micturition reflex is composed of autonomic neurons that control smooth bladder muscle (Detrusor) and somatic (voluntary) neurons that control the skeletal muscle of the external urethral sphincter (EUS). After SCI, the coordination between these muscles is lost and they contract spontaneously. While something is known about how SCI alters the excitability of neuronal pathways that feed into the spinal cord (afferents) and how SCI alters the excitability of these muscles, relatively little is known how excitability of the neurons (autonomic bladder-innervating neurons) contained in a collection of neurons called the major pelvic ganglia (MPG) is altered. The primary aim of this proposal is to characterize how the excitability of these neurons changes after acute (3 days post injury) and chronic (28 days post injury) SCI. Mouse models of SCI will be used to determine how injury alters the ability of neurons to fire based on their intrinsic properties (as opposed to their input from other neurons). Underlying mechanisms for altered output will be investigated using voltage clamp and pharmacological dissection of ionic currents to measure changes in underlying membrane conductance. To determine whether underlying changes in membrane conductance are the result of alterations in channel expression, single-cell quantitative RT-PCR (qRT-PCR) will be used to measure transcript numbers from MPG neurons in injured and intact animals. The proposed work will greatly improve the basic understanding of bladder reflex circuitry by providing a much needed extension of the characterization of the physiological properties and underlying ionic mechanisms of MPG neuron function. In addition, these studies represent one of the first analyses of plasticity at the MPG as a result of SCI, with implications for the successful comprehensive treatment of neurogenic bladder dysfunction.
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