Repetitive epileptogenic challenge: Neurophysiology and neuropharmacology in the amygdala

Periodic presentation of epileptogenic stimuli acts as a repetitive epileptogenic challenge (REC), causing seizure susceptibility and/or severity to become increased. Audiogenic seizure (AGS) kindling and chronic ethanol (CE) are two forms of REC. Studies suggest that the neuronal network expands from brainstem to the forebrain, including the amygdala (AMG) following REC. Electrophysiological changes in the structures of the expanded network are likely to occur in REC and were examined experimentally. The ability of histamine, a neuromodulator of seizures, to affect AGS kindled seizures was also evaluated.; Electroencephalography and immunocytochemistry studies indicate that AMG is involved in both AGS kindling and CE. Therefore, we hypothesized that: (1) Microinjection of histamine into AMG may reduce AGS severity increase following REC. (2) The neuronal firing in AMG in vivo may be increased following REC. (3) The auditory input pathway to the AMG from the medial geniculate body (MGB) in vivo may become hyperactive. (4) Changes in AMG neuron membrane and synaptic properties in vitro may occur after REC.; Microinjection of histamine into lateral nucleus of AMG (LAMG) of kindled severe strain genetically epilepsy-prone rats (K-GEPR-9s) significantly reduced the duration of the post-tonic clonus, which was rarely observed before AGS kindling. LAMG neuronal firing patterns in vivo were significantly altered and the neuronal responsiveness was enhanced after AGS kindling. The spontaneous neuronal activity in vivo was enhanced in LAMG of K-GEPR-9s. The threshold for LAMG neuronal response to MGB electrical stimulation in vivo was significantly below normal, and the mean number of action potentials in the LAMG was significantly elevated in K-GEPR-9s. In vitro studies found these electrophysiological changes were related to the alterations of GABA_A receptor function and were unlikely to be induced by the enhancement of glutamate receptor-mediated responses. These findings strongly indicate that AMG is a critical structure in AGS kindling, and the seizure network is partly expanded from MGB to AMG during AGS kindling process in GEPR-9s.; In “binge” ethanol treatment alone, LAMG neuronal responses in vivo were significantly decreased during ethanol administration and ethanol withdrawal (ETX) as compared to the pre-ethanol control. The responses of LAMG neurons were reduced with increasing rates of stimulation (habituation) in pre-ethanol control, but LAMG habituation was not observed during ethanol administration and ETX. The firing of LAMG neurons during ETX seizures remained suppressed although tonic firing was observed during tonus. After 28-day CE treatment, the first dose of ethanol in the “binge” protocol did not significantly suppress the LAMG neuronal firing. LAMG neuronal responses were significantly decreased during ETX as compared to those before “binge” treatment. Although the animals exhibited consistent increases in AGS severity, LAMG neuronal firing during ETX seizures was not different from that treated with “binge” ethanol alone. These findings suggest that LAMG is unlikely to be involved in the neuronal network for ETX seizures, and CE, although alters LAMG neuronal firing, fails to recruit LAMG into ETX seizure network.