GABAB receptor-mediated heterosynaptic depression (HD) has been demonstrated at mossy fibre-CA3 synapses (Min et al. 1998; Vogt & Nicoll, 1999). HD gates excitatory drive to the hippocampus and could limit seizure propagation. The source of GABA that mediates HD is unknown. GABA may be released by interneurons or mossy fibres (MFs) (Walker et al. 2001). Because following status epilepticus (SE) MFs have increased GABA content (Sloviter et al. 1996), we asked whether SE alters the magnitude of GABAB receptor-mediated HD.
Hippocampal slices from two groups of animals were used: healthy adult rats and rats after 2 h of either electrically induced SE (by stimulation of the perforant path under halothane anaesthesia) or pilocarpine-induced SE (administered by intraperitoneal injection). Animals were killed humanely 24 h after SE. All animal procedures followed the Animal (Scientific Procedures) Act, 1986. We positioned a recording electrode in stratum lucidum and placed two stimulation electrodes in the dentate gyrus to recruit two separate MF pathways. One MF pathway was used as the ‘test’ and the other as the ‘conditioning’ pathway.
MF fEPSPs were identified by marked facilitation with increasing stimulation frequency and inhibition by the group II mGluR agonist DCGIV (1 µM). The test pathway was stimulated at 0.05 Hz and a 50 Hz train of five pulses was applied to the conditioning pathway preceding every 10th stimulus of the test pathway. In healthy animals, stimulation of the conditioning MF pathway decreased fEPSPs in the test pathway to 79 ± 10 % (S.E.M.). This HD was abolished by the GABAB antagonist SCH50911 (20 µM, n = 5). However, in post-SE rats, there was no HD (102 ± 10 % of control, n = 6). The increase in GABA content of MFs after SE is not reflected by enhanced HD. This implies that the major source of GABA mediating HD in control animals is interneurons. A reduction in interneuron recruitment could lead to the subsequent development of spontaneous seizures in this model.
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Sloviter, R.S., Dichter, M.A., Rachinsky, T.L., Dean, E., Goodman, J.H., Sollas, A.L. & Martin, D.L. (1996). J. Comp. Neurol. 373, 593-618.
Vogt, K.E. & Nicoll, R.A. (1999). Proc. Natl Acad. Sci. 96, 1118-1122.
Walker, M.C., Ruiz, A. & Kullmann, D.M. (2001). Neuron 29, 703-715.