Granule cell hyperexcitability in the early post-traumatic rat dentate gyrus: the 'irritable mossy cell' hypothesis

1. Cytochemical and in vitro whole-cell patch clamp techniques were used to investigate granule cell hyperexcitability in the dentate gyrus 1 week aft er fluid percussion head trauma. 2. The percentage decrease in the number of hilar interneurones labelled wi th either GAD67 or parvalbumin mRNA probes following trauma was not differe nt from the decrease in the total population of hilar cells, indicating no preferential survival of interneurones with respect to the non-GABAergic hi lar cells, i.e. the mossy cells. 3. Dentate granule cells following trauma showed enhanced action potential discharges, and longer-lasting depolarizations, in response to perforant pa th stimulation, in the presence of the GABA, receptor antagonist bicucullin e. 4. There was no post-traumatic alteration in the perforant path-evoked mono synaptic excitatory postsynaptic currents (EPSCs), or in the intrinsic prop erties of granule cells. However, after trauma, the monosynaptic EPSC was f ollowed by late, polysynaptic EPSCs, which were not present in controls. 5. The late EPSCs in granule cells from fluid percussion-injured rats were not blocked by the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (APV), but were eliminated by both the non-NMDA glutamate receptor antagon ist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the AMPA receptor antag onist GYKI 53655. 6. In addition, the late EPSCs were not present in low (0.5 mM) extracellul ar calcium, and they were also eliminated by the removal of the dentate hil us from the slice. 7. Mossy hilar cells in the traumatic dentate gyrus responded with signific antly enhanced, prolonged trains of action potential discharges to perforan t path stimulation. 8. These data indicate that surviving mossy cells play a crucial role in th e hyperexcitable responses of the post-traumatic dentate gyrus.