Distribution of [H-3]MK-801, [H-3]AMPA and [H-3]kainate binding sites in rat hippocampal long-term slice cultures isolated from external afferents

The distribution of ionotropic glutamate receptors in transverse hippocampa l sections and along the septotemporal hippocampal axis can be correlated t o hippocampal connectivity, in particular to area- and layer specific termi nation zones of afferents. However, in isolated organotypic hippocampal sli ce cultures developing without extrinsic afferent input no systematic studi es exist about the distribution of glutamate receptors. In the present stud y we used receptor autoradiography to examine [H-3]MK-801, [H-3]AMPA and [H -3]Kainate binding sites in hippocampal slice cultures prepared from 6-day- old rats. After 24 days in vitro layer-specific concentrations of [H-3]MK-8 01, [H-3]AMPA and [H-3]Kainate binding sites were compared to age-matched h ippocampi in situ (P30 rats). An obvious difference between hippocampal sli ce cultures and hippocampi in situ was a changed distribution of binding si tes among the hippocampal areas showing a relative increase of [3H]MK-801 a nd [H-3]AMPA binding sites in CA3 as compared to CA1 and to the dentate gyr us in the cultures. In CA1, however, the relative layer-specific distributi ons of [H-3]MK-801 and [H-3]AMPA binding sites were identical in hippocampa l slice cultures and in hippocampi in situ. Interestingly, layer-specific b inding of [H-3]Kainate in the cultures exceeded that in the hippocampi in s itu 3-5 times. Moreover, in the cultures the binding of the three ligands v aried systematically showing gradients along the "superficiomembranal" axis . Cultures taken from different positions along the hippocampal axis differ ed with respect to concentrations of [H-3]MK-801 and [H-3]Kainate binding s ites, but: not of [H-3]AMPA binding sites. The results suggest a massive sp routing and reorganisation of intrinsic projections in long-term hippocampa l slice cultures.