Neuronal mechanisms of the anoxia-induced network oscillations in the rat hippocampus in vitro

1. A spindle of fast network oscillations precedes the ischaemia-induced ra pid depolarisation in the rat hippocampus in vivo. However, this oscillator y pattern could not be reproduced in slices and the underlying mechanisms r emain poorly understood. We have found that anoxia-induced network oscillat ions (ANOs, 20-40 Hz, lasting for 1-2 min) can be reproduced in the intact hippocampi of postnatal day P7-10 rats in vitro, and we have examined the u nderlying mechanisms using whole-cell and extracellular field potential rec ordings in a CA3 pyramidal layer. 2. ANOs were generated at the beginning of the anoxic depolarisation, when pyramidal cells depolarised to subthreshold values. Maximal power of the AN Os was attained when pyramidal cells depolarised to -56 mV; depolarisation above -47 mV resulted in a depolarisation block of pyramidal cells and a wa ning of ANOs. 3. A multiple unit activity in extracellular field recordings was phase loc ked to the negative and ascending phases of ANOs. Pyramidal cells recorded in current-clamp mode generated action potentials with an average probabili ty of about 0.05 per cycle. The AMPA receptor-mediated EPSCs and the GABA r eceptor-mediated IPSCs in CA3 pyramidal cells were also phase locked with A NOs. 4. ANOs were prevented by tetrodotoxin and glutamate receptor antagonists C NQX and APV, and were slowed down by the allosteric GABAA receptor modulato r diazepam. In the presence of the GABA(A) receptor antagonist bicuculline, ANOs were transformed to epileptiform discharges. 5. In the presence of the A1 adenosine receptor antagonist 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX), the anoxia induced an epileptiform. activity an d no ANOs were observed. 6. In normoxic conditions, a rise of extracellular potassium to 10 mM induc ed an epileptiform activity. Increasing extracellular potassium in conjunct ion with a bath application of the adenosine A1 receptor agonist cyclopenty ladenosine induced oscillations similar to ANOs. 7. Multisite recordings along the septo-temporal hippocampal axis revealed that ANOS and anoxic depolarisation originate in the temporal part, and pro pagate towards the septal pole at a speed of 1.9 mm min(-1). 8. ANOs were observed starting from P7, i.e. at a developmental stage when the effects of GABA change from depolarisation to hyperpolarisation. 9. These results suggest that the synchronisation of anoxia-induced oscilla tions relies on synaptic mechanisms; that the inhibition by GABA and adenos ine sets the tune for a generation of oscillations and prevents an epilepti form activity; and that a synchronous GABAergic inhibition is instrumental in a phase locking neuronal activity similarly to other types of oscillator y activities in the gamma frequency range.