A five-year training program providing the applicant with the opportunity to develop the knowledge and skills required to perform future independent investigations in synapse physiology and the basic mechanisms of epilepsy is proposed. Having completed clinical training in child neurology and clinical neurophysiology at Children's Hospital Boston, the principal investigator is now an Assistant Professor of Neurology and Pediatrics at the University of Virginia. The opportunity to expand upon his scientific skills under the mentorship of Dr. Jaideep Kapur, a recognized leader in the basic mechanisms of epilepsy, and the UVA Department of Neurology's commitment to this candidate makes UVA the ideal setting for the applicant's training as a physician-scientist. The proposed research will focus on providing an improved understanding of the changes that occur at inhibitory synapses during status epilepticus. First line therapies for the treatment of status epilepticus, which target inhibitory synaptic transmission, often fail leaving the patient at risk for mortality or significant neurological morbidity. It is posited that an improved understanding of the changes that occur at inhibitory synapses during status epilepticus will provide a framework on which to base new therapies with the goal of improving the prognosis for those who present in status epilepticus. While two distinct lines of evidence suggest that an alteration in inhibitory synaptic transmission does occur during status epilepticus and that this alteration is, in part, the result of a modification in the complement of GABAA receptors present at the synapse, the mechanism underlying the modification is not known. Using an in vitro and an in vivo model of status epilepticus combined with electrophysiological and cellular imaging techniques, the mechanism underlying the modification in the post-synaptic GABAA receptor population will be investigated by completing four Specific Aims: 1) To characterize the impact of in vitro status epilepticus on GABA-mediated synaptic transmission by means of patch clamp recording, 2) To characterize the impact of in vivo status epilepticus on GABA-mediated synaptic transmission by means of patch clamp recording, 3) To characterize the impact of status epilepticus on the rate of internalization and distribution of GABAA receptors by means of immunocytochemistry combined with microscopy and 4) To characterize the impact of status epilepticus on GABA release from the pre-synaptic terminals by means of patch clamp recording.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Clinical Investigator Award (CIA) (K08)
Project #
Application #
Study Section
NST-2 Subcommittee (NST)
Program Officer
Jacobs, Margaret
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Virginia
Schools of Medicine
United States
Zip Code
Sánchez Fernández, Iván; Abend, Nicholas S; Agadi, Satish et al. (2014) Gaps and opportunities in refractory status epilepticus research in children: a multi-center approach by the Pediatric Status Epilepticus Research Group (pSERG). Seizure 23:87-97
Donner, Elizabeth J; Goodkin, Howard P (2010) Pediatric epilepsy surgery: looking back while moving forward. Neurology 74:1756-7
Goodkin, Howard P; Quigg, Mark (2010) Toothbrushing EEG artifact recorded from chronically implanted subdural electrodes. Neurology 75:1850
Perrin, Margaret W; Sahoo, Sanjiv K; Goodkin, Howard P (2010) Latency to first psychogenic nonepileptic seizure upon admission to inpatient EEG monitoring: evidence for semiological differences. Epilepsy Behav 19:32-5
Rajasekaran, Karthik; Zanelli, Santina A; Goodkin, Howard P (2010) Lessons from the laboratory: the pathophysiology, and consequences of status epilepticus. Semin Pediatr Neurol 17:136-43
Goodkin, Howard P; Joshi, Suchitra; Mtchedlishvili, Zakaria et al. (2008) Subunit-specific trafficking of GABA(A) receptors during status epilepticus. J Neurosci 28:2527-38
Traul, David E; Traul, Christine S; Matsumoto, Julie et al. (2008) Acute encephalopathy with biphasic seizures and late restricted diffusion on MRI in a Japanese child living in the USA. Dev Med Child Neurol 50:717-9
Sheehan, Jason P; Jane, John A; Ray, Dibyendu K et al. (2008) Brain abscess in children. Neurosurg Focus 24:E6
Goodkin, Howard R; Joshi, Suchitra; Kozhemyakin, Maxim et al. (2007) Impact of receptor changes on treatment of status epilepticus. Epilepsia 48 Suppl 8:14-5
Buck, Marcia L; Gurka, Matthew J; Goodkin, Howard P (2007) Postmarketing modifications in the safety labeling of the new antiepileptics. Neurology 68:1536-7

Showing the most recent 10 out of 11 publications