Neural Circuits and Brainstem Control of LUT Function

 

project — From sensory signal to motor action

The brain coordinates sensory input from the lower spinal cord and pelvis and information from the external environment to ‘decide’ when to void, by activating or inhibiting neurons in the brain pontine micturition center, aka Barrington’s nucleus. 

Our goal is to identify the specific neurons that comprise i) the bladder-afferent activity sensing circuits and ii) the continence regulating neural circuits; both of which function critically within the reflex micturition pathway. 

The lab uses in vivo fiber photometry (1,2) to study the temporal sequence underlying Barrington’s nucleus neuron activation. Furthermore, we use neuroscience techniques such as opto- and chemogenetics and conditional ablation of neurons for manipulating neural activity (3-7), and to ‘connect’ neurons in specific ‘nodes’ of the micturition reflex pathway with roles in regulating spontaneous voiding.

 
>> This project investigates which neurons detect, relay and process the bladder distention signal, so that it ultimately becomes integrated into coherent neural control for proper bladder function. <<

- Funding: NIH/NIDDK, RO1 DK125708 (Verstegen – PI), 2020-2025 

References:

1) Lin et al., (2016) Nat Neurosci. 19, 1142-1153. 2) Chen et al., (2013) Nature 499, 295- 300. 3) Deisseroth. (2015) Nat Neurosci. 18, 1213-1225. 4) Atasoy and Sternson. (2018) Physiol Rev. 98, 391-418. 5) Roth. (2016) Neuron 89, 683-694. 6) Anaclet et al., (2018) J. Neurosci. 38, 5168-5181. 7) Todd et al., (2018) Nat Neurosci. 21, 717–724.

Read more:

Verstegen et al., 2019 - Non-Crh glutamatergic neurons in Barrington’s nucleus ... Current Biology 29, 2775-2789.


 
 
Schematic of ChR2.mCherry construct and viral targeting unilateral to a PMC-afferent brain site.

Schematic of ChR2-mCherry construct and viral targeting unilateral to a Barrington’s nucleus-afferent brain site.

Schematic of GCaMP6s construct and viral targeting unilateral to a PMC-afferent brain site.

Schematic of GCaMP6s construct and viral targeting unilateral to a Barrington’s nucleus-afferent brain site.