SEPTAL NEURON CHOLINERGIC AND GABAERGIC FUNCTIONS - DIFFERENTIAL REGULATION BY BASIC FIBROBLAST GROWTH-FACTOR AND EPIDERMAL GROWTH-FACTOR

Numerous studies suggest that growth and trophic factors play roles in the development and mature function of brain neurons. Recently, growt h factors whose actions were previously characterized on non-neuronal cells have been localized to the brain. We sought to determine whether these factors influence septal cholinergic function. Initially, we de fined the effects of basic fibroblast growth factor (bFGF) and epiderm al growth factor (EGF) on septal cholinergic cells in dissociated neur onal culture. Both factors elevated activity of the acetylcholine synt hetic enzyme, choline acetyltransferase (CAT). To determine whether th e factors acted directly on neurons or whether glia mediated the effec ts, a mitotic inhibitor, 5-fluorodeoxyuridine (FDUR), was added to the cultures to eliminate dividing glia. The action of EGF was completely blocked by the addition of FDUR. However, bFGF elevated CAT activity even in the presence of FDUR. Consequently, bFGF may regulate septal c holinergic function directly, whereas EGF may affect cholinergic cells indirectly through glia. To determine whether increases in CAT activi ty reflect increased enzyme activity per neuron or an increase in the number of cholinergic cells, bFGF-treated cultures were stained for ac etylcholinesterase (AChE) to determine numbers of cholinergic cells. N o differences in AChE-positive cells were noted, suggesting that bFGF increased CAT activity per cholinergic neuron. To determine whether bF GF regulates other populations in the septum, we examined GABAergic ne urons by monitoring the activity of glutamic acid decarboxylase (GAD), a GABA synthetic enzyme. Basic FGF significantly increased GAD activi ty; however, the effect was completely abolished by addition of FDUR. Thus, bFGF may act directly on cholinergic neurons and indirectly on G ABA cells. To define potential endogenous sources of bFGF, we employed Western blot analysis. Basic FGF was detected in pure septal glial cu ltures but not in pure neuronal cultures. Therefore, local glia may se rve as a source of bFGF in the septum. Our study suggests that multipl e factors potentially regulate septal cell function through different intercellular mechanisms. The multiplicity of factors and mechanisms a nd apparent redundancy, may play a critical role in normal ontogeny.