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                       BIOINFORMATICS COLLOQUIUM
                    School of Computational Sciences
                        George Mason University
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              The Influences of Excitatory and Inhibitory
           Synaptic Connections on the Patterns of Bursting
                      in a Neuronal Network Model

                              Susan Yang
             Johns Hopkins University School of Medicine, NIH

                        Tuesday, March 30, 2004
                                4:30 pm
                 Verizon Auditorium, Prince William Campus

The balance between inhibition and excitation plays a crucial role in
the generation of synchronous bursting activity in neuronal circuits. In
human and animal models of epilepsy, changes in both excitatory and
inhibitory synaptic inputs are known to occur. Locations and
distribution of these excitatory and inhibitory synaptic inputs on
pyramidal cells play a role in the integrative properties of neuronal
activity, e.g., epileptiform activity. Thus the location and
distribution of the inputs onto pyramidal cells are important parameters
that influence neuronal activity in epilepsy. However, the location and
distribution of inhibitory synapses converging onto pyramidal cells have
not been fully studied. The objectives of this study are to investigate
the roles of the relative location of excitatory as well as inhibitory
synapses on the dendritic tree and soma in the generation of bursting
activity. We hypothesize that a simplified multicompartment pyramidal
neuron model can produce such bursting activity by changing the synaptic
connectivity represented by the synaptic weight and delay. Then we
investigate influences of somatic and dendritic inhibition on bursting
activity patterns in several paradigms of potential connections using
this multicompartmental model. We also investigate the effects of
distribution of fast and slow components of GABAergic inhibition in
pyramidal cells. Interspike interval (ISI) analysis is used for
examination of bursting patterns. Simulations show that a simplified
pyramidal neuron model can accurately replicate bursting behavior and
the inhibitory interneuron regulates neuronal bursting
activity. Bursting behavior patterns depend on the synaptic weight and
delay of the excitatory and inhibitory connection as well as the
location of the synapse. When the inhibitory interneuron synapses on the
pyramidal neuron, inhibitory action is stronger if the inhibitory
synapse is close to the soma. Alterations of synaptic weight of the
interneuron can be compensatory for changes in the location of synaptic
input. The relative changes in these parameters exert a considerable
influence on whether synchronous bursting activity is facilitated or
reduced. Additional simulations show that the slow GABAergic inhibitory
component is more effective than the fast component in distal
dendrites. Taken together, these findings illustrate the potential for
GABAergic inhibition in the soma and dendritic tree to play an important
modulatory role in bursting activity patterns.

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