Projection of non-cholinergic basal forebrain neurons ensheathed with perineuronal nets to rat mesocortex

Abstract

The existence of non-cholinergic (GABAergic) components in the septo-hippocampal system but also in basal forebrain projections terminating in the olfactory bulb and certain cortical areas has been documented by several authors using retrograde and anterograde tracing techniques. On the other hand, the basal forebrain also contains a high number of mainly parvalbumin-positive neurons ensheathed by a lattice-like matrix of polyanionic proteoglycans forming so-called perineuronal nets of as yet unknown function. By a combination of retrograde tracing using Fluoro-Gold injections into mesocortical areas of rats and staining of perineuronal nets by Wisteria floribunda agglutinin (WFA) the present study describes the projection pattern and distribution of non-cholinergic projection neurons characterized by perineuronal nets in the anterior parts of the basal forebrain complex (medial septal nucleus, nucleus of the diagonal band of Broca, magnocellular preoptic nucleus). After tracer injection into the cingulate cortex labelled net-associated neurons were distributed within the rostrocaudal extension of the basal forebrain complex but were predominantly found in the horizontal limb of the diagonal band of Broca. Retrograde labelling of neurons with perineuronal nets after tracer injection into the retrosplenial cortex was more pronounced in the medial septum. Choline acetyltransferase-immunoreactive (ChAT-ir) projection neurons were in no case associated with perineuronal nets. The results demonstrate that a large portion of the non-cholinergic projection neurons of the basal forebrain are endowed with a specialized microenvironment of proteoglycans and form a strong input system of mesocortical components of the limbic system.