Department of Biological Sciences
office: Wilson West 011
The goal of my research is to develop mathematical
and computational models of individual neurons of the hippocampus that will
be appropriate for use in network models. The immediate focus is to develop
highly detailed models of dentate granule cells that describe appropriately
how computation and synaptic modification occur in these cells. These highly
detailed models must satisfy the constraints imposed by experimental data
including conditions leading to long-term potentiation (LTP) and long-term
Modeling work is proceeding on molecular, synaptic
and neuron levels. On the molecular level, a model of a dendritic spine is
being extended to include calcium binding to calmodulin and calmodulin
binding and trapping by CaM-kinase II with the hope of being able to express
the essence of these biochemical reactions in a synaptic modification rule.
On the synaptic level, diffusion models of the synaptic cleft have been
developed to determine more accurate descriptions of NMDA and AMPA
conductances for use in neuron level models. On the neuron level, detailed
morphology is being used in simulations to determine the range of
computational possibilities of neurons as constrained by the spatial and
temporal distribution of synaptic and non-synaptic conductances. Methods are
being developed to determine appropriate parameter values for the
- Li, Y. and Holmes, W.R.
2000. Comparison of CaMKinase II activation in a dendritic spine
computed with deterministic and stochastic models of the NMDA
synaptic conductance. Neurocomputing 32-33:1-7.
- Holmes, W.R. 2000. Models of
calmodulin trapping and CaM Kinase II activation in a dendritic spine.
J. Comput. Neurosci. 8:65-85.
- Aradi, I. and Holmes, W.R. 1999.
Active dendrites regulate spatio- temporal integration in hippocampal
dentate granule cells. Neurocomputing 26-27:45-51.
- Aradi, I. and Holmes, W.R.
1999. Role of multiple calcium and calcium-dependent conductances in regulation
of hippocampal dentate granule cell excitability. J. Comput. Neurosci.
- Holmes, W.R. and Aradi, I.
1998. Modeling the contributions of calcium channels and NMDA receptor
channels to calcium current in dendritic spines. In: Computional Neuroscience:
Trends in Research, 1998. J.M. Bower, editor. pp. 191-196.
- Holmes, W.R. and W.B. Levy
(1997) Quantifying the role of inhibition in associative long-term
dentate granule cells with computational models. J. Neurophysiol. 78:103-116.
are some jpg files showing results of a Stochastic model of glutamate release
at a synapse
At time = 1 ms
Small blue balls grouped into a larger ball represent glutamate molecules in
a synaptic vesicle
- white balls
represent glutamate uptake sites
- red arrows are
- blue balls are
NMDA receptors in the postsynaptic membrane
At time = 1 ms
All the glutamate has been released from the vesicle into the synaptic cleft.
Symbols same as above.
white arrows represent open non-NMDA receptor-channels and red balls are open