Research Interests: |
We use mathematical and computational models at three levels of organization, the neuron, the synapse, and biochemical reactions within dendritic spines, to study the mechanisms that lead to changes at individual synapses important for learning and memory. At the neuron level, work is being done to construct realistic models of individual CA1 hippocampal pyramidal neurons that can predict the voltage response to types of stimuli thought to be necessary for learning to occur. These simulations are performed with the NEURON simulator.
At the synapse level, work is being done to develop accurate descriptions of the NMDA and AMPA synaptic conductances that can be used in conjunction with neuron level models to predict calcium influx at synapses on dendritic spines during trains of stimuli. MCELL is often used for these simulations. At the biochemical level, calcium influx into dendritic spines is the starting point for modeling calcium initiated cascades of biochemical reactions involved in learning and memory. More recently our focus has been on the axon and how axons process information in both hippocampal and vestibular neurons. Another project in the lab is to develop computational models of zinc homeostasis in cortical neurons in collaboration with Dr. Colvin.
- Zeng S and Holmes WR. 2010. The effect of noise on CaMKII activation in a dendritic spine during LTP induction. J. Neurophysiol. 103:1798-1808.
- Grover LM, Kim E, Cooke JD, and Holmes WR. 2009. LTP in hippocampal area CA1 is induced by burst stimulation over a broad frequency range centered around delta. Learn. Mem. 16:69-81.
- Ambros-Ingerson J, Grover LM, and Holmes WR. 2008. A classification method to distinguish cell-specific responses elicited by current pulses in hippocampal CA1 pyramidal cells. Neural Comput. 20(6): 1512-1536.
- Colvin RA, Bush AI, Volitakis I, Fontaine CP, Thomas D, Kikuchi K, and Holmes WR. 2008. Insights into Zn2+ homeostasis in neurons from experimental and modeling studies. Am. J. Physiol: Cell Physiol 294:C726-C742.
- Holmes, WR and Grover LM. 2006. Quantifying the magnitude of changes in synaptic level parameters with long-term potentiation. J. Neurophysiol. 96:1478-1491.