Inhibitory function in two models of chronic epileptogenesis.
Although drug-induced disinhibition is a potent method for producing acute epileptogenesis, data with respect to possible disorders of GABAergic inhibitory function in models of chronic epilepsy are incomplete and inconsistent. We examined rat models of cortical post-traumatic epilepsy, and epileptogenic cortical microgyri. Results suggest enhanced rather than decreased inhibitory function in cortical networks in these preparations. In brain slices from epileptogenic chronically isolated cortex, the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) and miniature (m)IPSCs in layer V pyramidal neurons is increased compared to control. In the epileptogenic zone adjacent to the microgyrus, both spontaneous and stimulus-induced IPSCs are larger in amplitude than control, and the frequency of sIPSCs is more dependent upon glutamatergic excitation of interneurons than in control layer V neurons of homotopic cortex. Immunocytochemical studies show that there is enhanced immunoreactivity for several proteins in GABAergic interneurons of chronic cortical isolations, and suggest that there may be sprouting of GABAergic axons in the area of injury. This conclusion is supported by anatomic data showing an approximate doubling of the number of presumed inhibitory synapses on somata of layer V pyramidal neurons. These anatomic findings are consistent with the increased frequency of mIPSCs on these neurons. Inhibition is robust in both of these chronic models of epileptogenesis. Increased inhibitory electrogenesis might be pictured as part of the epileptogenic process, e.g. a mechanism for synchronizing the discharge of pyramidal neurons, or as a compensatory mechanism that might prevent the development of abnormal activities in some cases, or limit the intensity of epileptogenesis in others.
Prince
D A
DA
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, CA 94305-5122, USA. daprince@leland.stanford.edu
Jacobs
K
K
D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D064026:Calbindins; D002540:Cerebral Cortex / Q000002:abnormalities / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D005071:Evoked Potentials / Q000502:physiology*; D005615:Freezing; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D010320:Parvalbumins / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D009435:Synaptic Transmission
D064026:Calbindins; D009419:Nerve Tissue Proteins; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G