title: Pathological effect of homeostatic synaptic scaling on network dynamics in diseases of the cortex.
abstract: Slow periodic EEG discharges are common in CNS disorders. The pathophysiology of this aberrant rhythmic activity is poorly understood. We used a computational model of a neocortical network with a dynamic homeostatic scaling rule to show that loss of input (partial deafferentation) can trigger network reorganization that results in pathological periodic discharges. The decrease in average firing rate in the network by deafferentation was compensated by homeostatic synaptic scaling of recurrent excitation among pyramidal cells. Synaptic scaling succeeded in recovering the network target firing rate for all degrees of deafferentation (fraction of deafferented cells), but there was a critical degree of deafferentation for pathological network reorganization. For deafferentation degrees below this value, homeostatic upregulation of recurrent excitation had minimal effect on the macroscopic network dynamics. For deafferentation above this threshold, however, a slow periodic oscillation appeared, patterns of activity were less sparse, and bursting occurred in individual neurons. Also, comparison of spike-triggered afferent and recurrent excitatory conductances revealed that information transmission was strongly impaired. These results suggest that homeostatic plasticity can lead to secondary functional impairment in case of cortical disorders associated with cell loss.
authors.affiliation: The Salk Institute for Biological Studies, Computational Neurobiology Laboratory, La Jolla, California 92037, USA.
authors.forename: Flavio
authors.initials: F
authors.lastname: Fröhlich
authors.forename: Maxim
authors.initials: M
authors.lastname: Bazhenov
authors.forename: Terrence J
authors.initials: TJ
authors.lastname: Sejnowski
mesh_terms: D000818:Animals; D001927:Brain Diseases / Q000175:diagnosis / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000503:physiopathology*; D003198:Computer Simulation; D004569:Electroencephalography; D004660:Encephalitis / Q000503:physiopathology; D006706:Homeostasis; D006801:Humans; D007395:Interneurons / Q000378:metabolism; D008959:Models, Neurological; D009415:Nerve Net / Q000503:physiopathology*; D009473:Neuronal Plasticity / Q000502:physiology; D009475:Neurons, Afferent / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*
chemical_list: D024642:Potassium Channels, Voltage-Gated; D015222:Sodium Channels