title: Function of synapses in the CA1 region of the hippocampus: their contribution to the generation or control of epileptiform activity.
abstract: 1. In the kainic acid lesioned hippocampus there is a loss of functional inhibition that is associated with reduction of the IPSPs recorded intracellularly from the surviving CA1 pyramidal cells. The possible pre- or postsynaptic origin of this change has been investigated. 2. Iontophoretic application of GABA to the soma and dendrites of CA1 pyramidal cells indicated that there had been no change in the efficacy of the postsynaptic GABA receptors on these cells. 3. Although a pre-synaptic mechanism is implicated, at one week post lesion we were unable to find any difference in the Ca+ dependent K+ evoked release of endogenous GABA. However, at survival times greater than 1 week immunohistological studies showed a decrease in the number of somatostatin positive non-pyramidal cells in the stratum oriens of the CA1 area. 4. In addition to the reduction of functional inhibition, changes in excitatory neurotransmitter mechanisms were also found to contribute to the epileptiform burst discharge. A slow component of the epileptiform EPSP recorded from CA1 pyramidal cells has been recorded and was found to be antagonized by the NMDA-receptor antagonist D-APV. 5. Methods of controlling epileptiform activity in the kainic acid lesioned hippocampus have been tested. Stimulation of the substantia nigra and ventral tegmental areas produced profound inhibition of pyramidal cell activity in control hippocampi; however, they, were found to be ineffective in controlling the epileptiform burst. 6. A second method involved the use of hippocampal suspension grafts. Whilst this approach has yielded some encouraging data, further studies are necessary before the mechanism of the improvement in inhibitory synaptic function can be explained.
authors.affiliation: Department of Neurophysiology, Medical School, Southampton University, UK.
authors.forename: H V
authors.initials: HV
authors.lastname: Wheal
mesh_terms: D000818:Animals; D004827:Epilepsy / Q000503:physiopathology* / Q000628:therapy; D005333:Fetus; D006624:Hippocampus / Q000196:embryology / Q000502:physiology* / Q000637:transplantation; D008959:Models, Neurological; D009433:Neural Inhibition; D013378:Substantia Nigra / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D013681:Tegmentum Mesencephali / Q000502:physiology