title: Differences in kainate receptor involvement in hippocampal mossy fibre long-term potentiation depending on slice orientation.
abstract: Long-term potentiation (LTP) is a well-established experimental model used to investigate the synaptic basis of learning and memory. LTP at mossy fibre - CA3 synapses in the hippocampus is unusual because it is normally N-methyl-d-aspartate (NMDA) receptor-independent. Instead it seems that the trigger for mossy fibre LTP involves kainate receptors (KARs). Although it is generally accepted that pre-synaptic KARs play an essential role in frequency facilitation and LTP, their subunit composition remains a matter of significant controversy. We have reported previously that both frequency facilitation and LTP can be blocked by selective antagonism of GluK1 (formerly GluR5/Glu(K5))-containing KARs, but other groups have failed to reproduce this effect. Moreover, data from receptor knockout and mRNA expression studies argue against a major role of GluK1, supporting a more central role for GluK2 (formerly GluR6/Glu(K6)). A potential reason underlying the controversy in the pharmacological experiments may reside in differences in the preparations used. Here we show differences in pharmacological sensitivity of synaptic plasticity at mossy fibre - CA3 synapses depend critically on slice orientation. In transverse slices, LTP of fEPSPs was invariably resistant to GluK1-selective antagonists whereas in parasagittal slices LTP was consistently blocked by GluK1-selective antagonists. In addition, there were pronounced differences in the magnitude of frequency facilitation and the sensitivity to the mGlu2/3 receptor agonist DCG-IV. Using anterograde labelling of granule cells we show that slices of both orientations possess intact mossy fibres and both large and small presynaptic boutons. Transverse slices have denser fibre tracts but a smaller proportion of giant mossy fibre boutons. These results further demonstrate a considerable heterogeneity in the functional properties of the mossy fibre projection.
authors.affiliation: MRC Centre for Synaptic Plasticity, School of Physiology & Pharmacology, University of Bristol, BS8 1TD, UK. sherwoodjo@lilly.com
authors.forename: John L
authors.initials: JL
authors.lastname: Sherwood
authors.forename: Mascia
authors.initials: M
authors.lastname: Amici
authors.forename: Sheila L
authors.initials: SL
authors.lastname: Dargan
authors.forename: Georgia R
authors.initials: GR
authors.lastname: Culley
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Fitzjohn
authors.forename: David E
authors.initials: DE
authors.lastname: Jane
authors.forename: Graham L
authors.initials: GL
authors.lastname: Collingridge
authors.forename: David
authors.initials: D
authors.lastname: Lodge
authors.forename: Zuner A
authors.initials: ZA
authors.lastname: Bortolotto
mesh_terms: D000818:Animals; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D019599:Mossy Fibers, Hippocampal / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018092:Kainic Acid Receptors / Q000502:physiology*
chemical_list: D018092:Kainic Acid Receptors