Spreading depression triggers ictaform activity in partially disinhibited neuronal tissues.

There is unequivocal electrophysiological evidence that spreading depression (SD) can trigger epileptiform field potentials. In vitro experiments on human brain tissues indicated that γ-aminobutyric acid (GABA)-mediated inhibition prevented this process. Intra- and extracellular recordings of bioelectrical activities were performed in the rodent neocortex, hippocampus and amygdala after perfusion of low concentrations of the GABAA antagonist bicuculline and induction of SD by KCl application. Induction of SD in combined amygdala-hippocampus-cortex slices pre-treated with low concentration of bicuculline triggered epileptiform burst discharges in cortical as well as subcortical brain structures. Propagation of SD significantly depolarized the membrane, decreased the amplitude and duration of action potentials (APs) and after-hyperpolarization as well as the neuronal membrane input resistance and the amplitude of threshold potentials. Ten to twenty minutes after induction of SD, the pattern of APs changed from regular firing to a series of APs riding on an underlying paroxysmal depolarization shift before the appearance of typical ictaform activities. Changes of characteristic features of APs occurred after SD persisted during the appearance of epileptiform activities. These results indicate that SD increases neuronal excitability and facilitates synchronization of neuronal discharges in the presence of partial disinhibition of neuronal tissues. Our findings might explain the occurrence of seizures in neurological disorders with partial impairment of inhibitory tone, such as brain ischemia and epilepsy.

The effects of tetanic stimulation on plasticity of remote synapses in the hippocampus-perirhinal cortex-amygdala network.

In the temporal lobe, multiple synaptic pathways reciprocally link different structures. These multiple pathways play an important role in the integrity of the function of the temporal lobe and malfunction in this network has been suggested to underlie some neurological disorders such as epilepsy. To test whether the induction of long-term potentiation (LTP) in one temporal lobe structure would modulate functional synaptic plasticity in other structures of this network, tetanic stimulation was applied to the white matter of the perirhinal cortex, Schaffer collaterals of the hippocampus, or the external capsule in combined rat amygdala-hippocampus-cortex slices. This tetanic stimulation was accompanied by enhancement of the evoked field potential slope in the third layer of perirhinal cortex, hippocampal CA1 area, and the lateral amygdala. Induction of LTP in each of these structures was concomitant with increased evoked field potentials in the neighboring structures. Surgical disconnection of anatomical pathways between these structures inhibited this concomitant enhancement of the evoked field potential slope. Both NMDA and AMPA glutamate sub-receptors were involved in changes of synaptic plasticity elicited by induction of LTP in the neighboring structures. The present data indicate a reciprocal control among the perirhinal cortex, the amygdala, and the hippocampus plasticity. This could be important for the formation and retention of the medial temporal lobe-dependent memory and may play a role in the involvement of all different regions of the temporal lobe in pathological conditions such as epilepsy that affect this brain structure.

Sequential changes in neuronal activity in single neocortical neurons after spreading depression.

BACKGROUND: Cortical spreading depression (CSD) has an important role in migraine with aura. Prolonged neuronal depression is followed by a late excitatory synaptic plasticity after CSD. METHOD: Intra- and extracellular recordings were performed to investigate the effect of CSD on intracellular properties of mouse neocortical tissues in the late excitatory period. RESULTS: During CSD, changes in the membrane potentials usually began with a relatively short hyperpolarization followed by an abrupt depolarization. These changes occurred roughly at the same time point after CSD as the beginning of the negative extracellular deflection. Forty-five minutes after CSD, neurons showed significantly smaller amplitude of afterhyperpolarization and a reduced input resistance. Depolarization and hyperpolarization of the cells by constant intracellular current injections in this period significantly changed the frequency of the action potentials. CONCLUSION: These data indicate higher excitability of the neocortical neurons after CSD, which can be assumed to contribute to hyperexcitability of neocortical tissues in patients suffering from migraine.