PERSISTENT EXCITABILITY CHANGES IN THE PIRIFORM CORTEX OF THE ISOLATED GUINEA-PIG BRAIN AFTER TRANSIENT EXPOSURE TO BICUCULLINE

The development of long-lasting excitability changes after a single in tracerebral injection of bicuculline (1 mM) in a restricted region of the anterior piriform cortex was studied by means of simultaneous intr a- and extracellular recordings in the isolated guinea-pig brain prepa ration maintained in vitro by arterial perfusion. The transitory disin hibition induced by bicuculline revealed transient afterdischarges tha t were followed by the activation of a synaptic potential mediated by the recurrent propagation of the focal epileptiform activity along cor tico-cortical associative fibres. The epileptiform associative potenti al persisted for the duration of the experiment. Both the induction an d the long-term expression of the epileptiform associative potential w ere dependent on the activation of glutamatergic receptors of the NMDA type, as demonstrated by perfusion with the NMDA receptor antagonist 2-aminopentanoic acid (AP5) (100 mu M). After bicuculline washout, pir iform cortex neurons responded to afferent stimulation with a burst di scharge superimposed on a paroxysmal depolarizing potential. The early component of the burst was mediated by a Ca2+-dependent, non-synaptic potential located at the proximal apical dendrites and soma of layer II-III cells, since (i) it was abolished by membrane hyperpolarization , (ii) it was not affected by AP5, (iii) it was correlated with a curr ent sink in layer II, as demonstrated by current source density analys is of field potential laminar profiles, and (iv) it was abolished by c admium (2-5 mM) applied locally in layer II. The late component of the burst response (i) coincided in time with the extracellular epileptif orm associative potential, (ii) increased linearly in amplitude during membrane hyperpolarization, (iii) was blocked by AP5, and (iv) was co rrelated with an extracellular sink in layer lb, where the associative fibres contact the distal apical dendrites of piriform cortex neurons . The results presented here indicate that a transient focal disinhibi tion promotes persistent intrinsic and synaptic excitability changes i n piriform cortex neurons. These changes may be responsible for the pr opagation of epileptiform activity and for the induction of secondary epileptogenesis.