Neural Circuits and Brainstem Control of LUT Function
project — Mapping brainstem control of bladder filling and voiding
Neurons in Barrington’s nucleus (Bar) in the brainstem are both sufficient and necessary for regulating detrusor activity and voiding contractions. This project aims to define the anatomical and functional interfaces between these neurons and neurons that connect to them.
Our goal is to develop a complete map of the anatomy and functional brain circuits that regulate bladder filling and voiding.
We use retrograde tracing, including modified rabies virus labeling (1) and CTb, and (trans-synaptic) anterograde (2-5) tracing techniques, to identify the neurons that innervate critical neuronal subpopulations and to map the central nervous system (CNS) circuits in control of maintaining continence. We also perform Channelrhodopsin-Assisted-Circuit-Mapping (CRACM) (6,7) followed by optogenetic activation or inhibition of neurons. This allows us to detect and manipulate neuronal activity of specific, monosynaptically connected, neuron populations.
>> This project uses state of the art neural mapping methods, coupled with careful measurements of bladder function in awake and anesthetized states. This application further investigates how the brain integrates signals from the bladder and the external environment to control bladder filling and voiding <<
- Funding and collaboration on the project: NIH/NIDDK, R01 DK113030 (Zeidel - PI), 2017-2022 and R01 DK135541 (Zeidel - PI), 2023-2028
References:
1) Callaway and Luo., (2015) J. Neurosci. 35, p8979-8985. 2) Zingg et al., (2017) Neuron 93, p33-47. 3) Zhingg et al., (2020) J Neurosci. 40, 16 p3250-3267. 4) Tsai et al., (2022) Nat.Neurosci. 25, p659-674. 5) Verstegen et al., (2019) Current Biology 29, 2775-2789. 6) Hull et al., (2009) J. Neurosci. 29, p8991– 8995. 7) Petreanu et al., (2009) Nature 457, p1142-1145.
Read more:
Barrington’s nucleus contains predominantly glutamatergic neurons, as shown by the presence of a GFP reporter for the type 2 vesicular glutamate transporter (Vglut2) and absence of a reporter for the vesicular GABA/glycine transporter (Vgat). Panels (a) and (b) compare the distributions of Vglut2 (glutamatergic) and Vgat (GABAergic/ glycinergic) neurons, respectively.
Injecting CTb into the lumbosacral spinal cord retrogradely labels neurons in Barrington’s nucleus and the Locus Coeruleus (LC).