J Neurophysiol (May 1, 2003). 10.1152/jn.00898.2002
Submitted on Submitted 7 October 2002; accepted in final form 9 January 2003

Synapse Formation Between Isolated Axons Requires Presynaptic Soma and Redistribution of Postsynaptic AChRs

 ¹Department of Molecular and Cellular Neurobiology, Research Institute Neuroscience Vrije Universiteit, Faculty of Earth and Life Sciences, 1081 HV Amsterdam, The Netherlands; and  ²Neuroscience and Respiratory Research Groups, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada

Meems, Ryanne, David Munno, Jan van Minnen, and Naweed I. Syed. Synapse Formation Between Isolated Axons Requires Presynaptic Soma and Redistribution of Postsynaptic AChRs. J. Neurophysiol. 89: 2611-2619, 2003. The involvement of neuronal protein synthetic machinery and extrinsic trophic factors during synapse formation is poorly understood. Here we determine the roles of these processes by reconstructing synapses between the axons severed from identified Lymnaea neurons in cell culture, either in the presence or absence of trophic factors. We demonstrate that, although synapses are maintained between isolated pre- and postsynaptic axons for several days, the presynaptic, but not the postsynaptic, cell body, however, is required for new synapse formation between soma-axon pairs. The formation of cholinergic synapses between presynaptic soma and postsynaptic axon requires gene transcription and protein synthesis solely in the presynaptic neuron. We show that this synaptogenesis is contingent on extrinsic trophic factors present in brain conditioned medium (CM). The CM-induced excitatory synapse formation is mediated through receptor tyrosine kinases. We further demonstrate that, although the postsynaptic axon does not require new protein synthesis for synapse formation, its contact with the presynaptic cell in CM, but not in defined medium (no trophic factors), differentially alters its responsiveness to exogenously applied acetylcholine at synaptic compared with extrasynaptic sites. Together, these data suggest a synergetic action of cell-cell signaling and trophic factors to bring about specific changes in both pre- and postsynaptic neurons during synapse formation.