Fate of GABAergic septohippocampal neurons after fimbria‐fornix transection as revealed by in situ hybridization for glutamate decarboxylase mRNA and parvalbumin immunocytochemistry

Abstract

Many septohippocampal neurons are GABAergic and are affected by transection of the fimbria-fornix, like the septohippocampal cholinergic cells. Here we have studied the changes that occur in GABAergic septohippocampal neurons following fimbria-fornix transection. For labeling of septohippocampal projection neurons, adult Sprague-Dawley rats received injections of the fluorescent tracer Fluoro-Gold into the hippocampus 1 week prior to bilateral transection of the fimbria-fornix. After axotomy, rats were allowed to survive for varying periods ranging from 3 weeks to 18 months. Following fixation of the animals, sections through the septal region were either stained by in situ hybridization for glutamate decarboxylase (GAD) mRNA or immunostained for parvalbumin (PARV), which is known to be present in GABAergic septohippocampal neurons. In situ hybridization for GAD mRNA revealed no statistically significant changes in cell number 3 weeks and 6 months postlesion. In contrast, PARV-immunoreactive neurons were reduced to 35% of control 3 weeks postlesion. This value increased to 66% after 6 months of survival. As seen in the electron microscope, axotomized PARV-positive neurons exhibited characteristics of vital cells. Most neurons contained lysosomes associated with Fluoro-Gold, resulting from retrograde labeling prior to fimbria-fornix transection. We conclude that mainly PARV-containing GABAergic neurons in the medial septal nucleus (MS) project to the hippocampus and are thus heavily affected by the lesion but are able to survive and restore the synthesis of PARV. The lack of significant changes in the number of GAD mRNA-expressing cells is explained by the presence of numerous GABAergic MS neurons not projecting to the hippocampus.