CELLULAR MECHANISMS OF 4-AMINOPYRIDINE-INDUCED SYNCHRONIZED AFTER-DISCHARGES IN THE RAT HIPPOCAMPAL SLICE

1. We constructed a model of the in vitro rodent CA3 region with 128 p yramidal neurones and twenty-four inhibitory neurones. The model was u sed to analyse synchronized firing induced in the rat hippocampal slic e by 4-aminopyridine (4-AP), a problem simultaneously studied in exper iments in rat hippocampal slices. N-methyl-D-aspartate (NMDA) receptor s were blocked. 2. Consistent with a known action of 4-AP, unitary EPS Cs were assumed to be large and prolonged. With augmented EPSCs, spont aneous synchronized bursts occurred in the model if random ectopic axo nal spikes were present. We observed probable antidromic spikes and mi niature spikes experimentally. 3. Consistent with experiment, model sy nchronized bursts were preceded by a period of about 100 ms of increas ed unit activity and cell depolarization. In the model, this was cause d in part by EPSPs consequent to ectopic axonal spikes.4. After widesp read firing had begun, full-blown synchrony in the model required orth odromic EPSPs. A single synchronized burst, once initiated, could proc eed without further ectopic activity. 5.. A depolarizing change in rev ersal potential for dendritic GABA(A) favoured the occurrence of synch ronized after-discharges in the model. Consistent with this, bicuculli ne was found to block after-discharges in slices bathed in 4-AP (70 mu M) during NMDA blockade. 6. These data indicate that, even with synap tic inhibition present, ectopic spikes can 'set the stage' for synchro nized activity by depolarizing pyramidal cell dendrites, but that recu rrent orthodromic EPSPs are required for expression of this synchrony. When synaptic inhibition is present, EPSCs may need to be larger than usual for synchrony to take place. Secondary bursts in 4-AP appear to be driven in part by a depolarizing GABA(A)-mediated current.