This project is a collaborative research program between experimental a cellular neurophysiologist and applied mathematicians. The central aim of the project is to develop detailed computational models of microcircuits composed principal neurons and interneurons in the CA1 region hippocampus. In particular, these computational models will: 1) Be based on the latest data available from patch-clamp experiments dealing with ionic conductances, calcium and two-photon imaging, and cell morphology. 2) Use ionic channel models specifically designed to accurately reproduce the experimentally determined behavior. 3) Use full-cell morphologies; in particular, the same individual cells from which electrophysiology data have been taken will be digitized for the computational studies. 4) Develop new adaptive computational methods that can be used to speed up the computational simulations. A long-term goal of the project is to develop sufficiently accurate models of excitatory and inhibitory cell types in the hippocampus so that realistic simulations of small networks present in the hippocampus can be performed. These computational simulations are intended to be a tool to guide the development of new patch-clamp experiments that further explore the functional behavior of the hippocampal region. It is anticipated that the resulting studies will ultimately foster an improved understanding of how the hippocampal network stores and retrieves memories. Specific benefits of the proposed research and training objectives are: 1) New models will be developed of morphologically reconstructed neurons from which electrophysiological measurements have been obtained using multiple patch-clamp electrodes and/or calcium imaging. 2) New ionic conductance models will be constructed to accurately reproduce the experimental results. 3) New computational methods will be developed to speed up the compartmental model simulations. 4) New models will be developed to explore network interactions between excitatory and inhibitory neurons within the hippocampus. 5) Graduate students and postdoctoral researchers, recruited from the ranks of applied mathematicians interested in biological applications, will be trained in computational neuroscience.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS046064-01
Application #
6641896
Study Section
Special Emphasis Panel (ZRG1-MDCN-5 (50))
Program Officer
Talley, Edmund M
Project Start
2002-09-30
Project End
2006-08-31
Budget Start
2002-09-30
Budget End
2003-08-31
Support Year
1
Fiscal Year
2002
Total Cost
$199,973
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
Organized Research Units
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Kim, Yujin; Hsu, Ching-Lung; Cembrowski, Mark S et al. (2015) Dendritic sodium spikes are required for long-term potentiation at distal synapses on hippocampal pyramidal neurons. Elife 4:
Menon, Vilas; Musial, Timothy F; Liu, Annie et al. (2013) Balanced synaptic impact via distance-dependent synapse distribution and complementary expression of AMPARs and NMDARs in hippocampal dendrites. Neuron 80:1451-63
Sheffield, Mark E J; Edgerton, Gabrielle B; Heuermann, Robert J et al. (2013) Mechanisms of retroaxonal barrage firing in hippocampal interneurons. J Physiol 591:4793-805
Harnett, Mark T; Makara, Judit K; Spruston, Nelson et al. (2012) Synaptic amplification by dendritic spines enhances input cooperativity. Nature 491:599-602
Sheffield, Mark E J; Best, Tyler K; Mensh, Brett D et al. (2011) Slow integration leads to persistent action potential firing in distal axons of coupled interneurons. Nat Neurosci 14:200-7
Menon, Vilas; Spruston, Nelson; Kath, William L (2009) A state-mutating genetic algorithm to design ion-channel models. Proc Natl Acad Sci U S A 106:16829-34
Katz, Yael; Menon, Vilas; Nicholson, Daniel A et al. (2009) Synapse distribution suggests a two-stage model of dendritic integration in CA1 pyramidal neurons. Neuron 63:171-7
Rempe, Michael J; Spruston, Nelson; Kath, William L et al. (2008) Compartmental neural simulations with spatial adaptivity. J Comput Neurosci 25:465-80
Spruston, Nelson (2008) Pyramidal neurons: dendritic structure and synaptic integration. Nat Rev Neurosci 9:206-21
Katz, Yael; Kath, William L; Spruston, Nelson et al. (2007) Coincidence detection of place and temporal context in a network model of spiking hippocampal neurons. PLoS Comput Biol 3:e234

Showing the most recent 10 out of 15 publications