DISTINCTIVE MORPHOLOGICAL FEATURES OF A SUBSET OF CORTICAL-NEURONS GROWN IN THE PRESENCE OF BASAL FOREBRAIN NEURONS IN-VITRO

Basal forebrain cholinergic neurons (BFCNs) provide the major subcorti cal source of cholinergic input to cerebral cortex and play an importa nt role in regulating cortical activity. The present study examined th e ability of BFCNs to influence neocortical neuronal growth by examini ng effects of the presence of BFCNs on certain cortical neurons grown under the controlled conditions of dissociated cell culture. Initial e xperiments demonstrated distinctive morphological features of a popula tion of neurons (labeled with SMI-32, a monoclonal antibody to nonphos phorylated neurofilament proteins that labels pyramidal neurons in viv o) in cocultures containing basal forebrain (BF) and cortical cells. T hese neurons (large neurons immunoreactive for SMI-32 [SMI-32(+) neuro ns]) were characterized as having extensive axons, greater soma size, and more dendritic growth than did most SMI-32(+) neurons in the cultu res. Staining for SMI-32 in cocultures in which the cortical neurons w ere labeled with a fluorescent marker before adding the BF cells indic ated that virtually ail large SMI-32(+) neurons were of cortical origi n. Eliminating BFCNs with the selective cholinergic immunotoxin 192 Ig G-saporin resulted in a >80% decrease in the number of large SMI-32(+) neurons, although causing little damage to other cells in the treated cultures; this suggests that survival or maintenance of large SMI-32( +) neurons may depend on ongoing trophic support from BFCNs. Thus, pre sent findings suggest that BFCNs may provide powerful growth and/or su rvival-enhancing signals to a subset of cortical neurons.