TARGET DETERMINATION OF NEUROTRANSMITTER PHENOTYPE IN SYMPATHETIC NEURONS

While the majority of sympathetic neurons are noradrenergic, a minorit y population are cholinergic. At least one population of cholinergic s ympathetic neurons arises during development by a target-dependent con version from an initial noradrenergic phenotype. Evidence for retrogra de specification has been obtained from transplantation studies in whi ch sympathetic neurons that normally express a noradrenergic phenotype throughout life were induced to innervate sweat glands, a target norm ally innervated by cholinergic sympathetic neurons. This was accomplis hed by transplanting footpad skin containing sweat gland primordia fro m early postnatal donor rats to the hairy skin region of host rats. Th e sympathetic neurons innervating the novel target decreased their exp ression of noradrenergic traits and developed choline acetyltransferas e (ChAT) activity. In addition, many sweat gland-associated fibers acq uired acetylcholinesterase (AChE) staining and VIP immunoreactivity. T hese studies indicate that sympathetic neurons in vivo alter their neu rotransmitter phenotype in response to novel environmental signals and that sweat glands play a critical role in the cholinergic and peptide rgic differentiation of the sympathetic neurons that innervate them. T he sweat gland-derived cholinergic differentiation factor is distinct from leukemia inhibitory factor and ciliary neurotrophic factor, two w ell-characterized cytokines that alter the neurotransmitter properties of cultured sympathetic neurons in a similar fashion. Recent studies indicate that anterograde signalling is also important for the establi shment of functional synapses in this system. We have found that the p roduction of cholinergic differentiation activity by sweat glands requ ires sympathetic innervation, and the acquisition and maintenance of s ecretory competence by sweat glands depends upon functional cholinergi c innervation. (C) 1994 John Wiley and Sons, Inc.