Epilepsy is a major debilitating disorder of the central nervous system which is characterized by abnormal electrical activity of the brain. This disease affects the lives of millions of people. Although epilepsy can be treated in many cases with drug therapy, a significant number of patients are intractable to drug treatment.
The aim of this research plan is to determine the cellular mechanisms of epilepsy in humans, in order to assist in developing improved treatments of seizure disorders. The cellular mechanisms of seizure activity will be investigated by studying the electrical events which occur during the transition between normal and abnormal neuronal behavior in epileptic human tissue. The dentate gyrus holds a crucial position in the control of electrical activity of the hippocampus, a site of seizure initiation. Therefore, the electrical activity of neurons in the dentate gyrus will be examined with intracellular techniques using brain slices from rat, monkey and epileptic patients. Comparison of data from experiments carried out on three species should resolve several important issues concerning studies of human tissue. The influence of excitatory and inhibitory synaptic input on hyperexcitability of the dentate gyrus will be examined. The role neurotransmitters play in modulating neuronal activity will be examined in detail with respect to low frequency synaptic input. The results from the proposed experiments will provide greatly needed information concerning the physiological basis of seizure disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS023077-05
Application #
3406143
Study Section
Neurology A Study Section (NEUA)
Project Start
1986-07-01
Project End
1992-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
5
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Graduate Hospital (Philadelphia)
Department
Type
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19146
Masukawa, L M; Burdette, L J; McGonigle, P et al. (1999) Physiological and anatomical correlates of the human dentate gyrus: consequences or causes of epilepsy. Adv Neurol 79:781-94
Masukawa, L M; O'Connor, W M; Burdette, L J et al. (1997) Mossy fiber reorganization and its possible physiological consequences in the dentate gyrus of epileptic humans. Adv Neurol 72:53-68
Masukawa, L M; Wang, H; O'Connor, M J et al. (1996) Prolonged field potentials evoked by 1 Hz stimulation in the dentate gyrus of temporal lobe epileptic human brain slices. Brain Res 721:132-9
Burdette, L J; Hart, G J; Masukawa, L M (1996) Changes in dentate granule cell field potentials during afterdischarge initiation triggered by 5 Hz perforant path stimulation. Brain Res 722:39-49
O'Connor, W M; Masukawa, L; Freese, A et al. (1996) Hippocampal cell distributions in temporal lobe epilepsy: a comparison between patients with and without an early risk factor. Epilepsia 37:440-9
Masukawa, L M; O'Connor, W M; Lynott, J et al. (1995) Longitudinal variation in cell density and mossy fiber reorganization in the dentate gyrus from temporal lobe epileptic patients. Brain Res 678:65-75
Burdette, L J; Masukawa, L M (1995) Stimulus parameters affecting paired-pulse depression of dentate granule cell field potentials. II. Low-frequency stimulation. Brain Res 680:63-72
Uruno, K; O'Connor, M J; Masukawa, L M (1995) Effects of bicuculline and baclofen on paired-pulse depression in the dentate gyrus of epileptic patients. Brain Res 695:163-72
Uruno, K; O'Connor, M J; Masukawa, L M (1994) Alterations of inhibitory synaptic responses in the dentate gyrus of temporal lobe epileptic patients. Hippocampus 4:583-93
Strowbridge, B W; Masukawa, L M; Spencer, D D et al. (1992) Hyperexcitability associated with localizable lesions in epileptic patients. Brain Res 587:158-63

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