Rd. Traub et al., CELLULAR MECHANISMS OF 4-AMINOPYRIDINE-INDUCED SYNCHRONIZED AFTER-DISCHARGES IN THE RAT HIPPOCAMPAL SLICE, Journal of physiology, 489(1), 1995, pp. 127-140
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.