The long-term goal of the proposed research is to obtain information about basic mechanisms in the production of seizures. Slices of rat neocortex maintained in vitro will be used as a model system for the study of a novel type of epileptiform activity we have observed in immature animals. Quantitative neurophysiological techniques will be used to examine the contributions of synaptic potentials, changes in the extracellular ionic environment, and alterations in the characteristics of single calcium channels to the generation of epileptiform discharges. Using intracellular recording techniques, the alterations in membrane potential and input resistance associated with paroxysmal depolarizing shifts and long-lasting depolarizations (LLDs) will be determined. We will also ascertain whether a synaptic input with a demonstrable reversal potential initiates LLDs. Ion-selective microelectrodes will be used to examine the mechanisms underlying LLDs and to determine whether LLDs are an ictal event or a type of spreading depression. Ionic changes will be correlated wit simultaneously recorded changes in membrane potential. Finally, patch-clamp recordings of single ionic channels will be made to investigate the hypothesis that the transient changes in extracellular calcium concentration seen during epileptiform discharges result in alterations of channel properties. Clinical seizure disorders are a significant medical problem. The proposed research is directed toward a better understanding of the mechanisms underlying paroxysmal discharges in the brain. Research such as this will contribute to a better understanding of modes of communication among neurons and will eventually lead to advances in the management of clinical seizure disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS022373-08
Application #
3404665
Study Section
Neurology A Study Section (NEUA)
Project Start
1986-04-01
Project End
1996-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
8
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
Schools of Dentistry
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Albertson, Asher J; Williams, Sidney B; Hablitz, John J (2013) Regulation of epileptiform discharges in rat neocortex by HCN channels. J Neurophysiol 110:1733-43
Albertson, Asher J; Yang, Jianming; Hablitz, John J (2011) Decreased hyperpolarization-activated currents in layer 5 pyramidal neurons enhances excitability in focal cortical dysplasia. J Neurophysiol 106:2189-200
Skov, Jane; Andreasen, Mogens; Hablitz, John J et al. (2011) Baclofen and adenosine inhibition of synaptic transmission at CA3-CA1 synapses display differential sensitivity to K+ channel blockade. Cell Mol Neurobiol 31:587-96
Mathew, Seena S; Hablitz, John J (2011) Presynaptic NMDA receptors mediate IPSC potentiation at GABAergic synapses in developing rat neocortex. PLoS One 6:e17311
Hablitz, John J; Yang, Jianming (2010) Abnormal pyramidal cell morphology and HCN channel expression in cortical dysplasia. Epilepsia 51 Suppl 3:52-5
Hablitz, John J; Mathew, Seena S; Pozzo-Miller, Lucas (2009) GABA vesicles at synapses: are there 2 distinct pools? Neuroscientist 15:218-24
Campbell, Susan L; Hablitz, John J (2008) Decreased glutamate transport enhances excitability in a rat model of cortical dysplasia. Neurobiol Dis 32:254-61
Mathew, Seena S; Pozzo-Miller, Lucas; Hablitz, John J (2008) Kainate modulates presynaptic GABA release from two vesicle pools. J Neurosci 28:725-31
Mathew, Seena S; Hablitz, John J (2008) Calcium release via activation of presynaptic IP3 receptors contributes to kainate-induced IPSC facilitation in rat neocortex. Neuropharmacology 55:106-16
Campbell, Susan L; Mathew, Seena S; Hablitz, John J (2007) Pre- and postsynaptic effects of kainate on layer II/III pyramidal cells in rat neocortex. Neuropharmacology 53:37-47

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