The long-term objective of this research is to understand the neural mechanisms of epilepsy. This proposal focuses on the physiology and possible behavioral dysfunctions of kindled spontaneous interictal spikes (SISs) in the hippocampus. It is hypothesized that hippocampal SISs in the CA1 region results from spontaneous neuronal bursting in CA3, through synapses that undergo long-term potentiation. Spaced electrical stimulations through chronically indwelling electrodes in the hippocampus of the rat (kindling) will serve as a model of epilepsy. The CA3 and CA1 evoked responses following stimulation of the stratum oriens and stratum radiatum, and the hippocampal SIS rate in the animals will be studied after daily tetanizations until seizures are evoked. Similar time courses of change of evoked responses and SIS rate may suggest a common underlying mechanism, possibly long-term potentiation. In the seizing animals, the relations between seizures and SISs, and the behavioral (sleep) relation of seizures and SISs will be studied by 24-hour computer-aided recordings. The intracellular correlates of kindled interictal spikes will be studied in urethane-anaesthetized animals to reveal the depolarization and hyperpolarization that may accompany the different types of SISs. Hippocampal slices from kindled, especially spontaneously seizing rats, will be compared to normal rats in their ability to sustain SISs, in CA3/CA1 evoked population excitability, and in the intrinsic membrane properties of CA3 and CA1 neurons. In addition, the behavioral dysfunctions of the hippocampus in relation to the SISs will be studied in an open 8- arm maze. By manipulating the SIS rate by cessation of tetanizations, the relation between maze-performance and the frequency of SIS may be revealed. A better understanding of the interictal spikes may result in a more efficient diagnosis and perhaps in the treatment of epilepsy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS025383-01
Application #
3410673
Study Section
Biopsychology Study Section (BPO)
Project Start
1988-02-01
Project End
1991-01-31
Budget Start
1988-02-01
Budget End
1989-01-31
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Western Ontario
Department
Type
DUNS #
208469452
City
London
State
ON
Country
Canada
Zip Code
N6 3K7
Wu, K; Canning, K J; Leung, L S (1998) Functional interconnections between CA3 and the dentate gyrus revealed by current source density analysis. Hippocampus 8:217-30
Wu, K; Leung, L S (1998) Monosynaptic activation of CA3 by the medial perforant path. Brain Res 797:35-41
Leung, L S (1998) Generation of theta and gamma rhythms in the hippocampus. Neurosci Biobehav Rev 22:275-90
Wu, C; Leung, L S (1997) Partial hippocampal kindling decreases efficacy of presynaptic GABAB autoreceptors in CA1. J Neurosci 17:9261-9
Leung, L S; Brzozowski, D; Shen, B (1996) Partial hippocampal kindling affects retention but not acquisition and place but not cue tasks on the radial arm maze. Behav Neurosci 110:1017-24
Ma, J; Brudzynski, S M; Leung, L W (1996) Involvement of the nucleus accumbens-ventral pallidal pathway in postictal behavior induced by a hippocampal afterdischarge in rats. Brain Res 739:26-35
Leung, L S; Roth, L; Canning, K J (1995) Entorhinal inputs to hippocampal CA1 and dentate gyrus in the rat: a current-source-density study. J Neurophysiol 73:2392-403
Leung, L S; Zhao, D (1995) Glial potentials evoked by single afferent pulses in hippocampal CA1 area in vitro. Brain Res 697:262-5
Leung, L S; Shen, B (1995) Long-term potentiation at the apical and basal dendritic synapses of CA1 after local stimulation in behaving rats. J Neurophysiol 73:1938-46
Leung, L W (1995) Simulation of perforant path evoked field and intracellular potentials in hippocampal CA1 area. Hippocampus 5:129-36

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