Effects of fimbria-fornix and angular bundle transection on expression of the p75 NGFR mRNA by cells in the medial septum and diagonal band of Broca: correlations with cell survival, synaptic reorganization and sprouting

Abstract

Quantitative in situ hybridization techniques were used to examine the effects of lesions which sever hippocampal cholinergic and cortical afferents on p75 NGFR mRNA-expressing cells located in the medial septum (MS) and the vertical (VDB) and horizontal (HDB) limbs of the diagonal band of Broca. Animals received either bilateral tranection of the fimbria/fornix, unilateral transection of the angular bundle, or sham surgery. Four days later, animals were sacrificed and sections through the MS, VDB and HDB were processed for detection of the p75 NGFR mRNA using in situ hybridization techniques previously described ( Mol. Brain Res., 6 (1989) 275–287). Transection of the fimbria/ fornix and angular bundle differentially affected p75 NGFR-expressing cells in the MS, VDB and HDB within 4 days after injury, in ways which were consistent and correlate with subsequent effects on cell survival, synaptic reorganization and growth. In particular, in the MS and VDB, transection on the fimbria/fornix resulted in a significant decrease in the size of p75 NGFR-expressing cells (reductions of 25.9% and 15.1% respectively) which was accompanied by a significant reduction (37.9% and 12.7% fewer grains/cell) in relative levels of p75 NGFR mRNA. In contrast, in the HDB, transection of the fimbria/fornix had no significant effect on the average size of p75 NGFR-expressing cells: however, a significant increase (49%) in the mean relative level of p75 NGFR mRNA was observed which may, in turn, reflect a larger increase (as much as 2–3 fold) in the levels of p75 NGFR mRNA expressed by a subpopulation of hippocampally projecting cholinergic neurons located in the HDB. Finally, transection of the angular bundle resulted in small, but significant increases (9.4% and 10.9%) in relative levels of p75 NGFR mRNA in the MS and VDB, as well as an increase (19.6%) in the number of p75 NGFR mRNA-expressing cells in the HDB, on the injured side. No increases in p75 NGFR expression in the MS, VDB or HDB contralateral to the lesion were observed; however, a decrease in the size (6.9%) and a message content (19.4%) of p75 NGFR-expressing cells was detected in the MS contralateral to the lesion. Most importantly, all of these effects are consistent with the subsequent effects of these lesions on the survival of basal forebrain cholinergic cells, and the reorganization and growth of cholinergic afferents to the hippocampal formation. In addition, all of these effects were observed within 4 days following injury, which means that the effects occur rapidly enough for NGF to have a role in initiating and orchestrating some of the lesion-induced changes in the organization and growth of basal forebrain cholinergic projections which have been described. These data provide evidence for a link between NGF-related effects and lesion-induced changes in the organization and sprouting of cholinergic projections in the adult central nervous system.