Neural Circuits and Brainstem Control of LUT Function

Research Interests

We seek to understand how the brain controls the bladder.

 

Normal bladder function is controlled by neural circuitry in the brain and spinal cord. Bladder detrusor activity is regulated by Barrington’s nucleus and the periaqueductal gray (PAG) regions of the brain. However, how these brain sites are innervated, the types of excitatory neurons involved in the bladder/voiding reflex, and the mechanisms of action, remain unclear.

Barrington’s nucleus (Bar) in the brainstem is postulated to be the motor function execution center that receives information from within the brain and sends information to the spinal cord. Descending Bar neuron projections target spinal regions with motor neurons and interneurons that innervate the bladder and external urethral sphincter muscles. To dissect functional neural circuits, we activate or silence specific neuronal populations and study the effects of interventions on neuronal activity patterns and urinary behaviors. 

Our research aims to answer questions such as:

* What is the interoceptive signal that the bladder is full? How does this signal get converted to motor action? Which neurons are critical for these processes?

* Which neurons make up and are active in the micturition reflex pathway? What controls the neurons in Barrington’s nucleus to become active or not to activate (i.e., to pee or not pee)?

* What are the different subtypes of neurons in Barrington’s nucleus in the brainstem, and what are their specific roles in regulating behaviors? How can urination be voluntarily controlled (i.e., when it is not the right time)?

* The lower urinary tract (LUT) is differently innervated in biological males and females. Do distinct neural circuits exist for sex-specific control over LUT function? How does hormone signaling - at specific levels of the brain-bladder axis – affect LUT function, in males and females?

 

Disturbances in the central nervous system control of bladder and sphincter function can cause or contribute to lower urinary tract dysfunction (LUTD); therefore, understanding the control circuits is central to identifying new cellular and molecular targets, which in turn will inform the development of more clinically practical drugs.