Core B is an Animal Core, which will be directed by Douglas A. Coulter, and will be managed on a day to day basis by Dr. Mary Ellen Kelly. The Core will also involve the efforts of two Senior Technicians: Shareen Nelson and Alicia White. This core will generate all of the animals to be utilized in experiments in this Progam Project Grant proposal, including animals immediately in pilocarpine-induced status epilepticus (Moss proposal, Project 3), animals 1-21 days after status epilepticus (AllProjects), and chronically epileptic animals, 1-3 months after status epilepticus (AllProjects). All projects will require mice that experience pilocarpine-induced status epilepticus. and all experiments require mice to be behaviourally or electrographically monitored for seizure activity. In order to minimize potential variability between laboratories and because proper implementation of all aspects of this epilepsy model requires substantial investment by animal care personnel, we have chosen to develop a centralized core responsible for all our animal needs. Specifically the animal core will be responsible for induction of pilocarpine-induced SE, post-SE care, long- term video or video/EEC monitoring of our chronic mice in order to confirm the presence of electrographic and/or behavioural seizures, cannula implantation and administration of viruses and drugs, and all stereotaxic surgeries. One of the biggest impediments in epilepsy research is lack of adequately characterized, competently prepared animal models of this disorder. By combining animal model generation for all proposals within this Program Project Grant into one core facility, manned by experts in generation and characterization of animal models of epilepsy, this should facilitate all studies within the proposal. Additionally, this core will extend the ability of all investigators in the Program Project to conduct studies in which candidate mechanisms can be manipulated, and consequences on epileptogenesis assessed. Long-term video/EEG monitoring is a specialized, laborious, difficult and expensive undertaking, with few laboratories in the country able to competently conduct such studies. Providing this expert animal monitoring capability to all investigators enables experiments in Projects 1, 2 and 3 to move beyond cellular and circuit characterizations, and actually assess effects in whole animals, on the incidence and severity of epilepsy. This immediately expands the translational impact of all of these programs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS054900-04
Application #
8073040
Study Section
Special Emphasis Panel (ZNS1)
Project Start
Project End
Budget Start
2010-06-01
Budget End
2011-05-31
Support Year
4
Fiscal Year
2010
Total Cost
$251,938
Indirect Cost
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Trattnig, Sarah M; Gasiorek, Agnes; Deeb, Tarek Z et al. (2016) Copper and protons directly activate the zinc-activated channel. Biochem Pharmacol 103:109-17
Coulter, Douglas A; Steinhäuser, Christian (2015) Role of astrocytes in epilepsy. Cold Spring Harb Perspect Med 5:a022434
Ah Mew, Nicholas; McCarter, Robert; Daikhin, Yevgeny et al. (2014) Augmenting ureagenesis in patients with partial carbamyl phosphate synthetase 1 deficiency with N-carbamyl-L-glutamate. J Pediatr 165:401-403.e3
Abramian, Armen M; Comenencia-Ortiz, Eydith; Modgil, Amit et al. (2014) Neurosteroids promote phosphorylation and membrane insertion of extrasynaptic GABAA receptors. Proc Natl Acad Sci U S A 111:7132-7
Kahle, Kristopher T; Deeb, Tarek Z; Puskarjov, Martin et al. (2013) Modulation of neuronal activity by phosphorylation of the K-Cl cotransporter KCC2. Trends Neurosci 36:726-737
Deeb, Tarek Z; Nakamura, Yasuko; Frost, Greg D et al. (2013) Disrupted Cl(-) homeostasis contributes to reductions in the inhibitory efficacy of diazepam during hyperexcited states. Eur J Neurosci 38:2453-67
Hines, Rochelle M; Davies, Paul A; Moss, Stephen J et al. (2012) Functional regulation of GABAA receptors in nervous system pathologies. Curr Opin Neurobiol 22:552-8
Padgett, Claire L; Lalive, Arnaud L; Tan, Kelly R et al. (2012) Methamphetamine-evoked depression of GABA(B) receptor signaling in GABA neurons of the VTA. Neuron 73:978-89
Jacob, Tija C; Michels, Guido; Silayeva, Liliya et al. (2012) Benzodiazepine treatment induces subtype-specific changes in GABA(A) receptor trafficking and decreases synaptic inhibition. Proc Natl Acad Sci U S A 109:18595-600
Gonzalez, Claudia; Moss, Stephen J; Olsen, Richard W (2012) Ethanol promotes clathrin adaptor-mediated endocytosis via the intracellular domain of ?-containing GABAA receptors. J Neurosci 32:17874-81

Showing the most recent 10 out of 48 publications