Poster abstracts
Poster number 85 submitted by Cameron Ford
Differential Regulation of Ependymal Ciliary Beat Frequency by Neuromodulators and Neurotransmitters
Cameron Ford (Neuroscience Graduate Department), Candice Askwith (Neuroscience Graduate Department ), Kirk Mykytyn (Molecular, Cellular and Developmental Biology Program)
Abstract:
Ependymal cells line the ventricular system of the brain and extend motile cilia into the cerebrospinal fluid (CSF). Coordinated beating of these cilia is thought to drive directional CSF flow, which is essential for nutrient distribution, metabolic waste clearance, and normal brain development and homeostasis. Disruption of ependymal cilia function or CSF dynamics is associated with neuroinflammation and neurological disorders, including hydrocephalus and neurodegenerative disease. While neuromodulators and neurotransmitters are present in the CSF and have been shown to influence ependymal ciliary beat frequency (CBF), the extracellular signals and cellular mechanisms governing this regulation remain poorly defined. Here, using pharmacological manipulation, we demonstrate that exposure to adenosine and norepinephrine robustly increases CBF. Adenosine-induced elevations are reversible upon washout, whereas norepinephrine produces a sustained elevation in CBF that persists following ligand removal. These effects are mimicked by forskolin, a protein kinase A (PKA) activator, consistent with modulation through intracellular signaling pathways. In contrast, exposure to serotonin and GABA decreases CBF. We have found that ependymal cells segregate into distinct responder and non-responder subpopulations. Response prevalence varies by ventricular region, with serotonin and GABA exhibiting regional response rate specificity between the dorsal third ventricle and the lateral ventricles. Together, these findings reveal functional heterogeneity among ependymal cells and identify neuromodulatory signals that bidirectionally regulate ciliary dynamics. Our results support a model in which ependymal cells actively sense and integrate neuromodulatory input to dynamically adjust CBF in response to changes in extracellular components, rather than functioning solely as passive drivers of fluid movement. Ongoing work aims to define the specific receptors and intracellular signaling mechanisms underlying this modulation. Elucidation of these pathways may provide insight into how altered transmitter signaling and CSF dynamics contribute to neurological disease and reveal new targets for therapeutic intervention.
Keywords: Ependymal Cilia, NeurotransmittersNeuromodulators, Ciliary beat frequency (CBF)