With the development of modern immunocytochemical and intracellular electrophysiological techniques, the complexity of local circuitry in hippocampus has become apparent. Although the hippocampus is a relatively simple cortical structure, it is thought to participate in complex information processing tasks. The diversity of interneuron types, their transmitters, and their local circuitry must be key elements in providing the system with the means of modulating the activity of primary projection cells. In the present application, we continue our study of those interneurons and local circuitries. Further, we propose to initiate a series of studies examining the effects of various """"""""traumatic"""""""" treatments on the interneurons of hippocampus, and the consequences of damaging specific vulnerable cell populations. The studies will be carried out on parallel, but closely interacting, tracks. Morphological characterization, by light and electron n=microscopic/immunocytochemical techniques, will describe the locations, arborization patterns, and putative neurotransmitter content of specific interneuron populations in the CA1, CA3, and dentate regions of rat hippocampus. These studies will also provide guidance for in vitro slice electrophysiological investigations with will attempt to characterize interneurons on the basis of their electrophysiological properties and their synaptic inter-actions with principal cell types (using simultaneous intracellular recordings of cell pairs). Interneurons will be intracellularly labeled and examined, in turn, at the morphological level. The same morphological and electrophysiological techniques will be used to assess the effects of various treatments on hippocampal interneurons and interneuron-dependent circuitry. Ischemia, anoxia, and stimulation treatments will be delivered to intact animals, which will be examined morphologically, and from which hippocampal slices will be obtained from electrophysiological investigation. Parallel treatments will be carried out in slices while recording from suspected vulnerable interneurons. Procedures will be developed to """"""""protect"""""""" vulnerable interneurons from effects of these treatments. These studies will provide a descriptive basis for understanding interneurons and interneuron local circuitry in hippocampus, and will test a number of specific hypotheses regarding interneuron action in hippocampus.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS018895-09
Application #
3398941
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1983-01-01
Project End
1993-12-31
Budget Start
1991-01-01
Budget End
1991-12-31
Support Year
9
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Kinoshita, Yoshito; Wenzel, H Jurgen; Kinoshita, Chizuru et al. (2012) Acute, but reversible, kainic acid-induced DNA damage in hippocampal CA1 pyramidal cells of p53-deficient mice. Epilepsia 53 Suppl 1:125-33
Knight, Leena S; Wenzel, H Jurgen; Schwartzkroin, Philip A (2012) Inhibition and interneuron distribution in the dentate gyrus of p35 knockout mice. Epilepsia 53 Suppl 1:161-70
Wenzel, H Jurgen; Tamse, Catherine T; Schwartzkroin, Philip A (2007) Dentate development in organotypic hippocampal slice cultures from p35 knockout mice. Dev Neurosci 29:99-112
Tschuluun, Naranzogt; Wenzel, H Jurgen; Schwartzkroin, Philip A (2007) Irradiation exacerbates cortical cytopathology in the Eker rat model of tuberous sclerosis complex, but does not induce hyperexcitability. Epilepsy Res 73:53-64
Tschuluun, N; Wenzel, J H; Katleba, K et al. (2005) Initiation and spread of epileptiform discharges in the methylazoxymethanol acetate rat model of cortical dysplasia: functional and structural connectivity between CA1 heterotopia and hippocampus/neocortex. Neuroscience 133:327-42
Wenzel, H Jurgen; Patel, Leena S; Robbins, Carol A et al. (2004) Morphology of cerebral lesions in the Eker rat model of tuberous sclerosis. Acta Neuropathol (Berl) 108:97-108
Patel, Leena S; Wenzel, H Jurgen; Schwartzkroin, Philip A (2004) Physiological and morphological characterization of dentate granule cells in the p35 knock-out mouse hippocampus: evidence for an epileptic circuit. J Neurosci 24:9005-14
Lopantsev, V; Wenzel, H J; Cole, T B et al. (2003) Lack of vesicular zinc in mossy fibers does not affect synaptic excitability of CA3 pyramidal cells in zinc transporter 3 knockout mice. Neuroscience 116:237-48
Lopantsev, Valeri; Tempel, Bruce L; Schwartzkroin, Philip A (2003) Hyperexcitability of CA3 pyramidal cells in mice lacking the potassium channel subunit Kv1.1. Epilepsia 44:1506-12
Lopantsev, V; Schwartzkroin, P A (2001) GABA(A)-dependent chloride influx modulates reversal potential of GABA(B)-mediated IPSPs in hippocampal pyramidal cells. J Neurophysiol 85:2381-7

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