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Intellectual and Developmental Disabilities Research Center

Houston, Texas

Intellectual and Developmental Disabilities Research Center
Intellectual and Developmental Disabilities Research Center
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Ionic Homeostasis and Seizure Regulation

The goal of this project is to explore the role seizure-induced alterations in intracellular calcium concentrations play in the morphological and physiological changes induced by seizures in early-life. Our previous studies have shown that seizure-like activity in developing hippocampal neurons in slice cultures suppresses dendrite growth and synapse formation. We have also shown that this is an NMDA receptor dependent process. Since activation of NMDA receptors leads to large increases in intracellular calcium, we have hypothesized that intracellular calcium signaling plays a crucial role in this process.

The goal of the studies planned is to use 2-photon microscopy coupled with whole cell patch clamp recordings to fully characterize where within hippocampal pyramidal cells calcium concentrations change when seizures occurs. The sources of intracellular calcium will be identified using pharmacological and genetic tools. Our ultimate goal is to identify the molecular mechanisms that underlie the effects seizures have on brain development in order to develop new strategies to prevent the progression of epilepsy and cognitive deficits commonly seen in individuals with a history of intractable childhood epilepsy .

Relevance of the project to IDDRC mission:

Seizure-induced alterations in intracellular calcium likely play a causative role in both the progression of an epileptic syndrome and cognitive impairments that are often reported in patients. The goal of this program is to further an understanding of the cellular changes in calcium activity that occur during seizure-like discharges in a relevant in vitro model system and the molecular consequences of these changes.

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