Dentate gyrus control of perforant path throughput to CA3 in a computational model
The dentate gyros is the main input circuitry to the hippocampus, but its role in cognitive processing and disease is poorly understood due in part to the low activity of the principle cell in this circuit. The dentate gyros undergoes many changes in diseases such as epilepsy, traumatic brain injury and autism but the alterations in circuit dynamics is not easy to determine in experimental preparations. A realistic computer simulation of the dentate slice preparation was constructed based on published anatomical data. The model used the seven major cell classes of the dentate, estimates of the number of synapses each class makes, and distributions of synapses based on axonal morphology. The network is randomly connected within these constraints and cell classes are connected if their corresponding axonal and dendritic fields overlap. In total, the model contains 35,465 cells and over 12 million intrinsic synapses. In addition, input cells of the entorhinal cortex are modeled similarly to provide stimulation to the network in a physiologically natural manner. Outputs of the network include action potential raster plots, transmembrane potentials, realistic local field potentials and construction of voltage-sensitive dye imaging. Simulations demonstrate robust gamma frequency oscillations, modulated gamma oscillations during theta frequency stimulation, gamma oscillations following tetanic stimulation, and altered physiology in a model of temporal lobe epilepsy. Additionally, the model is used to investigate the contribution to gain modulation made by activation of extrasynaptic GABAA receptors by GABA spillover from nearby synapses, and demonstrates that spillover mediated activation can account for the tonic current in granule cells and this tonic inhibition provides stronger gain modulation in the network than phasic inhibition alone. These simulations provide the first hippocampal model created with anatomical fidelity and demonstrate that in spite of the large heterogenity of the network, robust oscillations are generated similar to those observed in vitro. ^
Biology, Neuroscience|Engineering, Biomedical
Stephen D Cranstoun,
"Dentate gyrus control of perforant path throughput to CA3 in a computational model"
(January 1, 2008).
Dissertations available from ProQuest.