Intrinsic excitability, synaptic potentials, and short-term plasticity in human epileptic neocortex.

Although studies of epileptic human hippocampus suggest changes of synaptic and intrinsic excitability, few changes, save the appearance of spontaneous field/synaptic potentials, are known in epileptic neocortical tissue. However, invasive EEG and histological studies suggest that neocortical tissue, even in mesial temporal lobe epilepsy, can play an important role as an irritative zone or extrahippocampal focus. We hypothesized that intrinsic neuronal and synaptic excitability, as well as short-term plasticity, are altered in neocortical areas, particularly with elevated K+ levels as occur during seizures. We analyzed neuronal firing properties, synaptic responses, and paired-pulse plasticity in human neocortical slices from tissue resected during epilepsy surgery, both under normal and under pathological conditions, i.e., after elevating K+ (4/8 mM), with rat neocortical slices as controls. Neuronal firing properties were not different. We did find, however, alterations of synaptic responsiveness in epileptic tissue, i.e., an elevated network excitability with K+ elevations, and reduction of paired-pulse depression.

Increased excitability in cortico-striatal synaptic pathway in a model of paroxysmal dystonia.

Dystonias are movement disorders whose pathomechanism is largely unknown. Dystonic dt(sz) hamsters represent a model of primary dystonias, where alterations of striatal interneuron density and sodium channel function in projection neurones were described. Here, using cortico-striatal slices, we explore whether also the communication between neocortex and striatum is altered in dt(sz) hamsters. Field and intracellular recordings were done in dorsomedial striatum. Electrical stimulation was used to mimic neocortical afferents. Neuronal characteristics, synaptic connections, input-output relations and short- and long-term plasticity were analysed. Regarding cellular properties, striatal neurons of affected animals showed no alterations. Concerning network properties, evoked responses at threshold stimulation were mediated by (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptors. In dt(sz) slices, field responses, paired-pulse accentuation and LTP were larger than in control, possibly by an increase in presynaptic release probability at glutamatergic synapses. In summary, the study indicates that a change of cortico-striatal communication is involved in the manifestation of paroxysmal dystonia in the dt(sz) mutant.