CHOLINERGIC INNERVATION OF CEREBRAL-CORTEX IN ORGANOTYPIC SLICE CULTURES - SUSTAINED BASAL FOREBRAIN AND TRANSIENT STRIATAL CHOLINERGIC PROJECTIONS

Slices of entire forebrain hemispheres were taken from early postnatal rat pups and maintained as organotypic dice cultures. Basal forebrain cholinergic neurons, identified by histochemical staining for acetylc holinesterase, develop axons that grow rapidly into cerebral cortex. I ngrowth occurs by two routes: some axons course laterally from the bas al forebrain region to reach lateral neocortex; others course dorsally from the septum to reach medial cortex. By one to two weeks in vitro, acetylcholinesterase-positive axons have extended throughout most of the cortical territory. In addition to basal forebrain cholinergic axo ns, the normally local circuit cholinergic neurons of the striatum als o send axons into cerebral cortex. These striatum-derived axons can be distinguished from basal forebrain axons by their distinct morphologi cal characteristics and by their different response to excision of the striatum or basal forebrain. Further, acetylcholinesterase-positive a xons in cortex that originate from striatum appear to retract or degen erate after about one week in culture, while those from basal forebrai n remain present and apparently healthy beyond two weeks. These data d ocument the basal forebrain cholinergic ingrowth into cerebral cortex using this whole hemisphere slice culture system and also demonstrate different degrees of maintenance of cortical afferents that are derive d from different subcortical sources.