Defective function of GABA-containing synaptic vesicles in mice lacking the AP-3B clathrin adaptor.

AP-3 is a member of the adaptor protein (AP) complex family that regulates the vesicular transport of cargo proteins in the secretory and endocytic pathways. There are two isoforms of AP-3: the ubiquitously expressed AP-3A and the neuron-specific AP-3B. Although the physiological role of AP-3A has recently been elucidated, that of AP-3B remains unsolved. To address this question, we generated mice lacking mu3B, a subunit of AP-3B. mu3B-/- mice suffered from spontaneous epileptic seizures. Morphological abnormalities were observed at synapses in these mice. Biochemical studies demonstrated the impairment of gamma-aminobutyric acid (GABA) release because of, at least in part, the reduction of vesicular GABA transporter in mu3B-/- mice. This facilitated the induction of long-term potentiation in the hippocampus and the abnormal propagation of neuronal excitability via the temporoammonic pathway. Thus, AP-3B plays a critical role in the normal formation and function of a subset of synaptic vesicles. This work adds a new aspect to the pathogenesis of epilepsy.

Ictal dipole source analysis based on a realistic scalp-skull-brain head model in localizing the epileptogenic zone.

The objective of this study is to examine whether dipole modeling based on a realistic scalp-skull-brain head model (SSB/DT) is useful to localize the epileptogenic zone. Eight patients with surgically treated temporal lobe epilepsy were studied. Dipole locations and vector moments of ictal epileptiform activities were calculated by inverse solution methods. Accuracy of dipole locations were assessed by comparing with intracranial EEG. The patterns of ictal epileptiform activities were correlated with the dipole location and vector moment. Dipole locations of the peaks of ictal epileptiform activities estimated by SSB/DT showed good agreement with the epileptogenic foci determined by intracranial EEG. SSB/DT was able to discriminate between medial and lateral temporal epileptogenic foci. Two distinctive types of dipole vector moments, vertical and horizontal were noted. Vertical dipole vector moments corresponded to the medial temporal dipole source and horizontal dipole vector moments were corresponded to the lateral temporal dipole source. Useful clues to differentiate between medial and lateral temporal lobe epilepsy by the visual inspection of scalp EEG were found. SSB/DT is useful tool in the presurgical evaluation of patients with intractable epilepsy.

Different patterns of dipole source localization in gelastic seizure with or without a sense of mirth.

Dipole source localization corresponding to interictal spikes were estimated using EEG dipole tracing with a realistic three-shell head model in three patients with cryptogenic gelastic epilepsy. The dipole sources in two patients, whose gelastic seizures were accompanied by a subjective feeling of mirth, were estimated in the right or left medio-basal temporal regions. In the other patient, with gelastic seizures without a sense of mirth, the dipole sources were localized in the right frontal region corresponding to the anterior cingulate. The results suggest that the neural activities in hippocampal regions are involved with the generation of gelastic seizures with a sense of mirth and those in the cingulate might be associated with the motor act of laughter.