Todd A Fiacco
University of California-Riverside, CA·Neuroscience
Brain cells swell and shrink constantly, and the space between them changes with sleep, alertness and how hard neurons are firing. Controlling that swelling is not just housekeeping: when cells swell, they open channels that dump chemicals into the surrounding fluid, and some of those chemicals excite neurons.
- Fields
Neuroscience
Physiology
Biology
- Topics
astrocytes
volume-regulated anion channel
cell volume regulation
- Grants
- 1 known grant, through Nov 2029
What they work on
- Determine how much the volume-regulated anion channel in astrocytes contributes to brain tissue swelling and seizure generation in living mice, using astrocyte-specific conditional knockout animals.
- Test whether astrocytic VRAC is required for epilepsy to develop, combining overexpression of the channel with rescue strategies that restore it in conditional knockout mice.
- Identify the cellular mechanisms by which astrocytic VRAC alters neuronal excitability and regulates astrocyte volume, examining swelling-activated release of glutamate, the brain's main excitatory transmitter, in brain tissue.
- Assess whether loss of astrocytic VRAC changes epilepsy-associated pathology, including hippocampal sclerosis and neuronal cell loss.
More about the research
This project asks whether that process, running in astrocytes — the star-shaped support cells that outnumber neurons and regulate the brain's extracellular environment — helps generate seizures and drive the development of epilepsy.
Why it matters
Current anti-seizure drugs often cause cognitive side effects because they act broadly on neurons. Showing that a swelling-activated channel in astrocytes drives seizures and epilepsy development would offer a different kind of target, one aimed at support cells rather than neurons. The mechanisms studied also bear on cerebral edema, stroke, ischemia and Alzheimer's disease, where brain swelling and excess glutamate contribute to damage.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Alexander Mongin
Albany Medical College, NY·Neuroscience
Test whether LRRC8A-containing volume-regulated anion channels (VRACs) control extracellular taurine and GABA, inhibitory brain chemicals, using microdialysis in mice with brain-specific LRRC8A deletion that develop lethal seizures.
Peter Nelson
University of Kentucky, KY·Neuroscience
Test whether the ABCC9 gene variant linked to LATE+HS risk lowers ABCC9 expression in human astrocytes, using RNA-Seq to map transcripts and splicing and immunohistochemistry on genotyped human brains.
Shelley J Russek
Boston University, MA·Neuroscience
Test whether STAT3 signaling in excitatory neurons drives epilepsy progression by silencing synaptic plasticity and neuroinflammation genes, using mice with neuron-specific STAT3 knockout in the intrahippocampal kainate model.
The school
University of California-Riverside: 21 labs on PI Pages, $232M a year on research, 328 research doctorates a year.
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