Spread and arrest of seizures: the importance of layer 4 in laminar interactions during neocortical epileptogenesis.
Much of the past investigation of epileptogenesis has centered on characterizing the paroxysmal depolarization shift (PDS) and postulating its origin. Spatial as well as functional analyses of cortical epileptic foci have been few in number, and in nearly all of them fully evolved drug foci, which were used for their stability, probably obscured differences in the responsivity among constituent neuronal populations at earlier stages of epileptic evolution. Proportionately little attention has been directed at determining where penicillin acts within the cortex. For the past 12 years, we have addressed both issues. Specific questions have included, for both individual neurons and neuronal aggregates: what are the initial abnormalities of responsiveness in an acute epileptic focus; how do these abnormalities evolve as the focus develops; is there a differential susceptibility of various neocortical layers to epileptogenesis; how do the various cortical laminar populations interact during epileptogenesis; how do the resultant response abnormalities propagate within and between cortical columns; and what are the effects of anticonvulsants on the various spatial and temporal features of epileptogenesis? In pursuit of this information, we have recorded the evolution of discrete and temporary epileptic foci in cat striate cortex, which were induced by the microinjection or iontophoresis of penicillin into the different cortical layers. Simultaneous, multilaminar responses of individual neurons and of neuronal aggregates to selective visual stimulation have been characterized before, during, and after focus development using multibarrel micropipettes. Correlations between drug diffusion and these multilaminar recordings were made periodically by using 14C-labeled penicillin. Stages: Using these techniques, new characteristics of focal epilepsy come to light that are not apparent in the spontaneous spiking of the typical established penicillin focus. Three successive stages of penicillin-induced epileptogenic abnormality were noted in the responses of isolated neurons: (a) an initial graded enhancement of the primary latency response to field-specific stimuli into a burst discharge (the EPR burst); (b) the subsequent graded development of a longer latency burst in response to field-specific and nonspecific stimuli (the LR burst); and (c) the evolution of a single stereotyped burst discharge (IIS) as the latency separating EPR and LR bursts declined (PDS or LR discharge). Each type of neuronal burst was accompanied by a local field potential of similar latency, but of progressively increasing amplitude, with each successive stage of epileptogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)
J S
JS
Ebersole
A B
AB
Chatt
D000200:Action Potentials; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D001640:Bicuculline / Q000494:pharmacology; D001696:Biomechanical Phenomena; D002415:Cats; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D004198:Disease Susceptibility; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D008959:Models, Neurological; D009434:Neural Pathways / Q000503:physiopathology; D009474:Neurons / Q000502:physiology; D010406:Penicillins / Q000494:pharmacology; D010634:Phenobarbital / Q000627:therapeutic use; D010672:Phenytoin / Q000627:therapeutic use; D011930:Reaction Time
D000927:Anticonvulsants; D010406:Penicillins; D010672:Phenytoin; D001640:Bicuculline; D010634:Phenobarbital