Cholinergic modulation of status epilepticus in the rat barrel field region of primary somatosensory cortex

Abstract

Status epilepticus (SE) represents a serious medical emergency that can produce long-lasting brain damage as well as cognitive and memory deficits. However, the mechanisms that determine the emergence of SE from a single seizure and the prolonged duration of SE are unknown. Therefore, we used pharmacological tools to investigate the cellular mechanisms that underlie this prolonged epileptic activity in the rat barrel field region of somatosensory cortex (S1BF). Electrocortical and unitary extracellular field recording in the rat S1BF region was used to assess abnormal epileptiform activity induced by intracerebral application of 4-aminopyridine (4-AP). Simultaneously, electromyographic (EMG) activity was recorded from mystacial pad musculature. Intracerebral injection of 4-AP induced an SE that was paralleled by an increase of whisker activity that was not synchronized with the electrocortical recording. The seizures were originated ipsilaterally in the cortex of the injected hemisphere and propagated to the contralateral cortex with lower amplitude. The application of the glutamatergic NMDA receptor antagonist d (−)-2-amino-5-phosphonopentanoic acid (AP5) strongly increased the seizure-onset latency. The muscarinic receptor antagonist atropine changed the continuous rapid spiking pattern of SE to periodic discharges, while glutamatergic or GABAergic antagonist did not modify the electrographic features of SE. Our data suggest that the muscarinic cholinergic system plays an important role in the seizure modulation during SE in the somatosensory cortex, while their emergence is controlled, in part, by glutamatergic NMDA receptors.