CHOLINERGIC FUNCTION IN THE HIPPOCAMPUS OF JUVENILE RATS CHRONICALLY DEPRIVED OF NGF

Intracellular and extracellular recordings were used to assess the cho linergic function in hippocampal slices from juvenile rats chronically deprived of NGF. NGF was neutralised by implanting into the lateral v entricle of postnatal (P) day 2 rats, alpha D11 hybridoma cells (secre ting monoclonal antibodies specific for NGF). Parental myeloma cells ( P3U) were used as controls. At P15-P18, slow cholinergic EPSPs could b e elicited in cells from both cu D11- and P3U-treated rats. However, s lices from alpha D11-implanted rats exhibited a 50% reduction in acety lcholine release following stimulation of cholinergic fibres. This eff ect was associated to a significant increase in the sensitivity of pyr amidal cells to carbachol, as suggested by the shift to the left of th e dose/response curve. This may reflect a compensatory mechanism for t he reduced efficacy of cholinergic innervation in NGF-deprived rats. I n both alpha D11- and P3U-treated rats, carbachol was able to induce a similar concentration-dependent depression of the field EPSPs, evoked by Schaffer collateral stimulation, suggesting that presynaptic musca rinic receptors were not altered. In rats implanted with alpha D11 cel ls at P15 and sacrificed at P21-P24, no changes in the sensitivity to carbachol were found. At this developmental stage, no differences in a cetylcholine release were observed between P3U- and alpha D11-treated animals. These results provide physiological evidence for a regulatory role of NGF in the cholinergic function of the hippocampus during pos tnatal development. (C) 1998 Elsevier Science B.V. All rights reserved .