Thursday, April 25, 2024
4/25/2024
DESCRIPTION (provided by applicant): The objective of the proposed experiments is to identify temporal and spatial patterns of pudendal afferent neuron activity during natural bladder behaviors and to determine whether these patterns can be mimicked with external stimuli to produce better control of bladder functions than achieved by conventional non-specific pudendal afferent stimulation. A secondary objective is to identify putative flow receptors within the urethra that may detect turbulent flow and mediate an excitatory micturition reflex through the pudendal nerve. The first specific aim is to quantify the neural sensory coding of the lower urinary tract. Recording electrodes, initially single tungsten wires and subsequently multi-electrode arrays will be used to record single unit activity from sacral afferent neurons. The firing pattern and rate of these neurons will be recorded during a series of controlled bladder function conditions, correllated with physiological variables, then used to quantify sensory coding of relevant physiological parameters. The second aim is to measure the physiological urinary responses to biomimetic patterns of electrical stimulation. The patterns of stimulation will be based on the patterns of sensory neuron activity decoded from the initial recordings and applied by multi-electrode arrays. Continence and micturition responses will be characterized during bladder filling and emptying then compared to the responses evoked by non- selective electrical stimulation of pudendal nerve afferents at 10 Hz (continence) and 33 Hz (micturition). The third aim is to identify the putative flow receptors within the urethra to determine whether the putative flow receptors are Pacinian corpuscles. Urethral tissue will be harvested immediately after sacrifice, then treated with a variety of staining reagents and observed using light microscopy. Identified structures will be characterized by location along the length of the urethra, size, and distance to the lumen wall to test the plausibility of each structure as a potential flow receptor. The long-term goal of this research is to develop an implantable, pacemaker-like device that can be used to restore bladder function in persons with neurological injury or disease. The results of the proposed studies will develop and establish the feasibility of using biomimetic stimulation of the sacral dorsal root ganglia and will guide development of a device intended for eventual use in humans.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
