# Intraspinal circuits supporting synergy between the bladder and urethral sphincter in mice

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $335,808

## Abstract

Project summary
Detrusor-sphincter-dyssynergia (DSD) is a major urological problem inducing inefficient voiding, increased
amount of post-void residual urine and high intravesical pressure after spinal cord injury (SCI). Until recently the
majority of studies on spinal mechanisms of coordination between external urethral sphincter (EUS) and the
bladder (BL) were conducted in female rats, although in clinical practice DSD develops more often in males.
Furthermore, sexual dimorphism in anatomy and function of the lower urinary tract (LUT) suggests differences
in the spinal neural circuits of male and female. With development of genetic modifications and optogenetic
techniques the mouse model of LUT dysfunction is becoming more useful than the rat. Therefore, in the
proposed project “Intraspinal circuits supporting synergy between the bladder and urethral sphincter in
mice” we will use transgenic mice of both sexes for electrophysiological, optogenetic, immunohistochemical,
pharmacological and anatomical studies of spinal cord circuits involved in interaction between the bladder (BL)
and the external urethral sphincter (EUS) in spinal intact animals and after spinal cord injury.
 We will test several hypotheses in in vivo and in vitro experiments. In urethane anesthetized animals of
both sexes, we will determine functional differences in spinal regulation of micturition and in control and SCI
mice. Male and female animals will be also used to determine hypothesized sexual dimorphism in LUT-related
spinal circuits and their plasticity after chronic SCI. Using electrical stimulation of the Lumbar Spinal Coordinating
Center (LSCC) which we have recently discovered in L3/L4 spinal segments, we will test whether an external
command can initiate voiding. Using trans-synaptic viral labeling, we will trace neuronal populations involved in
coordination between EUS and BL to determine structural and functional differences in LUT spinal networks
between males and females. In spinal cord slice preparations, we will use transgenic mice expressing channel
rhodopsin (ChR2) in inhibitory or excitatory neurons to study reactions of EUS motoneurons to light-evoked
activity of LUT-related spinal interneurons embedded in specific spinal pathways, and will identify and
characterize the inhibitory circuit which is responsible for EUS relaxation. We will define the role of the L3/L4
LSCC in activity of EUS motoneurons and EUS relaxation and its mode of interaction with L6/S1 motor neuronal
pool. We will evaluate the contribution of a hypothesized recurrent inhibitory circuit in L6/S1 to the generation of
EUS bursting and relaxation as well as to bladder-sphincter coordination.
 The long-term objectives of the research project are to increase our understanding of the
pathophysiological mechanisms inducing DSD and voiding problems after SCI and to develop new and effective
therapeutic interventions for the treatment of DSD in spinal cord disorders. Considering gender relate...

## Key facts

- **NIH application ID:** 10841047
- **Project number:** 5R01DK129194-04
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** SERGEI V KARNUP
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $335,808
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10841047

## Citation

> US National Institutes of Health, RePORTER application 10841047, Intraspinal circuits supporting synergy between the bladder and urethral sphincter in mice (5R01DK129194-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10841047. Licensed CC0.

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