Homeostatic synaptic plasticity can explain post-traumatic epileptogenesis in chronically isolated neocortex.
Chronically isolated neocortex develops chronic hyperexcitability and focal epileptogenesis in a period of days to weeks. The mechanisms operating in this model of post-traumatic epileptogenesis are not well understood. We hypothesized that the spontaneous burst discharges recorded in chronically isolated neocortex result from homeostatic plasticity (a mechanism generally assumed to stabilize neuronal activity) induced by low neuronal activity after deafferentation. To test this hypothesis we constructed computer models of neocortex incorporating a biologically based homeostatic plasticity rule that operates to maintain firing rates. After deafferentation, homeostatic upregulation of excitatory synapses on pyramidal cells, either with or without concurrent downregulation of inhibitory synapses or upregulation of intrinsic excitability, initiated slowly repeating burst discharges that closely resembled the epileptiform burst discharges recorded in chronically isolated neocortex. These burst discharges lasted a few hundred ms, propagated at 1-3 cm/s and consisted of large (10-15 mV) intracellular depolarizations topped by a small number of action potentials. Our results support a role for homeostatic synaptic plasticity as a novel mechanism of post-traumatic epileptogenesis.
The Salk Institute, Computational Neurobiology Laboratory, La Jolla, CA 92037, USA. arthur@salk.edu
Arthur R
AR
Houweling
Maxim
M
Bazhenov
Igor
I
Timofeev
Mircea
M
Steriade
Terrence J
TJ
Sejnowski
D000200:Action Potentials / Q000502:physiology; D000208:Acute Disease; D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000503:physiopathology*; D002415:Cats; D002908:Chronic Disease; D003714:Denervation; D004567:Electrodes, Implanted; D004827:Epilepsy / Q000209:etiology / Q000503:physiopathology*; D006706:Homeostasis / Q000502:physiology; D008959:Models, Neurological; D019579:Neocortex / Q000503:physiopathology*; D009473:Neuronal Plasticity / Q000502:physiology*; D010507:Periodicity