ADAPTIVE COUPLED NEURAL SYSTEM MODEL FOR HIPPOCAMPAL FUNCTION RESTORATION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The nervous system is comprised of network of neurons connected in an intricate and organized manner. Recent research offers potential treatment options for cognitive and memory loss accompanying Alzheimer's disease and other forms of dementia using system model-based stimulation. Coupled oscillator model with tunable parameters is proposed here to address the lack of adaptivity in these models. We hypothesize that: (1) variable oscillator model parameters related to single cell synaptic memory can be expanded to represent neuronal network kernel memory for large networks; and (2) neuronal activities at selective frequencies related to memory can be enhanced depending on the orientation of electrical stimulation. During the report period, we were successful in developing and validating the oscillator models from single cell to hippocampal slice dynamics. The concept of synaptic memory for a single cell can be extended into network kernel memory, hence drastically reducing the complexity of the computer model for large neuronal assemblies. The effects of the autapses related to the firing rate of action potentials and sub-threshold oscillations were also studied. Finally, the modulation of neuronal activities using the concept of stochastic resonance was investigated in the computer model and in vitro experiments. Our experimental results indicated that 5Hz network activity can be enhanced when the field stimulation was aligned parallel to the Subiculum-CA3 junction. Enhanced 40Hz activity was observed when the stimulation was applied perpendicular to the CA3-CA1 junction. For the direction for future studies, we will investigate the effect of Poisson distributed spike train stimulation frequency on the signal variability and reproducibility of the computer and in vitro models. A new algorithm for obtaining the numerical synaptic coupling factors is currently being developed as the building block for the long term application.