The proposed Program uses approaches within the disciplines of neuroanatomy, neuropharmacology, and neurophysiology to study a) factors that confer susceptibility to epileptogenesis in immature neocortex; b) electrophysiological abnormalities in injured neurons from hyperexcitable partially isolated neocortex; c) excitatory neurotransmission in developing and injured neocortex; d) changes in membrane and synaptic events in dentate gyrus following kindling; and e) noradrenergic disinhibition in hippocampal neurons. The specific projects are: I: Regulation of Neuronal Excitability and Epileptogenesis; II: Changes in Neuronal Excitability During Kindling-Induced Epilepsy; III: Regulation of Neuronal Excitability by Norepinephrine; and IV. Development of Excitatory Synaptic Transmission in Cortex. The techniques employed include intracellular current clamp and single electrode voltage clamp recordings; applications of patch clamp techniques to mature and immature neurons in in vitro slices for recording spontaneous and evoked synaptic currents and single channel activities; intracellular and retrograde neuronal labelling; applications of neurotransmitter agonists and antagonists to neurons; and induction of chronic hyperexcitability through kindling and creation of partially isolated cortical areas. The long-term goals of the Program are to obtain information which will provide a better understanding of the pathogenesis of epilepsy and insights which will lead to the development of rational new approaches to the prevention and treatment of this disorder. The studies outlined will also contribute to our understanding of normal regulation of cerebral excitability through effects of functional connections, specific transmitter systems, and intrinsic neuronal properties.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
5P50NS012151-19
Application #
3107659
Study Section
Neurological Disorders Program Project Review B Committee (NSPB)
Project Start
1975-06-01
Project End
1996-05-31
Budget Start
1993-06-01
Budget End
1994-05-31
Support Year
19
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Gu, Feng; Parada, Isabel; Shen, Fran et al. (2017) Structural alterations in fast-spiking GABAergic interneurons in a model of posttraumatic neocortical epileptogenesis. Neurobiol Dis 108:100-114
Takahashi, D Koji; Gu, Feng; Parada, Isabel et al. (2016) Aberrant excitatory rewiring of layer V pyramidal neurons early after neocortical trauma. Neurobiol Dis 91:166-81
Prince, David A (2014) How do we make models that are useful in understanding partial epilepsies? Adv Exp Med Biol 813:233-41
Tani, Hiroaki; Dulla, Chris G; Farzampour, Zoya et al. (2014) A local glutamate-glutamine cycle sustains synaptic excitatory transmitter release. Neuron 81:888-900
Jin, Xiaoming; Jiang, Kewen; Prince, David A (2014) Excitatory and inhibitory synaptic connectivity to layer V fast-spiking interneurons in the freeze lesion model of cortical microgyria. J Neurophysiol 112:1703-13
Mantoan Ritter, Laura; Golshani, Peyman; Takahashi, Koji et al. (2014) WONOEP appraisal: optogenetic tools to suppress seizures and explore the mechanisms of epileptogenesis. Epilepsia 55:1693-702
Dulla, C G; Tani, H; Brill, J et al. (2013) Glutamate biosensor imaging reveals dysregulation of glutamatergic pathways in a model of developmental cortical malformation. Neurobiol Dis 49:232-46
Ma, Yunyong; Ramachandran, Anu; Ford, Naomi et al. (2013) Remodeling of dendrites and spines in the C1q knockout model of genetic epilepsy. Epilepsia 54:1232-9
Carter, Matthew E; Brill, Julia; Bonnavion, Patricia et al. (2012) Mechanism for Hypocretin-mediated sleep-to-wake transitions. Proc Natl Acad Sci U S A 109:E2635-44
Zhang, Wei; Huguenard, John R; Buckmaster, Paul S (2012) Increased excitatory synaptic input to granule cells from hilar and CA3 regions in a rat model of temporal lobe epilepsy. J Neurosci 32:1183-96

Showing the most recent 10 out of 32 publications