title: Neuronal somata and extrasomal compartments play distinct roles during synapse formation between Lymnaea neurons.
abstract: Proper synapse formation is pivotal for all nervous system functions. However, the precise mechanisms remain elusive. Moreover, compared with the neuromuscular junction, steps regulating the synaptogenic program at central cholinergic synapses remain poorly defined. In this study, we identified different roles of neuronal compartments (somal vs extrasomal) in chemical and electrical synaptogenesis. Specifically, the electrically synapsed Lymnaea pedal dorsal A cluster neurons were used to study electrical synapses, whereas chemical synaptic partners, visceral dorsal 4 (presynaptic, cholinergic), and left pedal dorsal 1 (LPeD1; postsynaptic) were explored for chemical synapse formation. Neurons were cultured in a soma-soma or soma-axon configuration and synapses explored electrophysiologically. We provide the first direct evidence that electrical synapses develop in a soma-soma, but not soma-axon (removal of soma) configuration, indicating the requirement of gene transcription regulation in the somata of both synaptic partners. In addition, the soma-soma electrical coupling was contingent upon trophic factors present in Lymnaea brain-conditioned medium. Further, we demonstrate that chemical (cholinergic) synapses between soma-soma and soma-axon pairs were indistinguishable, with both exhibiting a high degree of contact site and target cell type specificity. We also provide direct evidence that presynaptic cell contact-mediated, clustering of postsynaptic cholinergic receptors at the synaptic site requires transmitter-receptor interaction, receptor internalization, and a protein kinase C-dependent lateral migration toward the contact site. This study provides novel insights into synaptogenesis between central neurons revealing both distinct and synergistic roles of cell-cell signaling and extrinsic trophic factors in executing the synaptogenic program.
authors.affiliation: Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Alberta T2N 4Z6, Canada.
authors.forename: Fenglian
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Alberta T2N 4Z6, Canada.
authors.forename: Collin C
authors.initials: CC
authors.lastname: Luk
authors.affiliation: Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Alberta T2N 4Z6, Canada.
authors.forename: Ryanne
authors.initials: R
authors.lastname: Wiersma-Meems
authors.affiliation: Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Alberta T2N 4Z6, Canada.
authors.forename: Kelly
authors.initials: K
authors.lastname: Baehre
authors.affiliation: Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Alberta T2N 4Z6, Canada.
authors.forename: Cameron
authors.initials: C
authors.lastname: Herman
authors.affiliation: Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Alberta T2N 4Z6, Canada.
authors.forename: Wali
authors.initials: W
authors.lastname: Zaidi
authors.affiliation: Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Alberta T2N 4Z6, Canada.
authors.forename: Noelle
authors.initials: N
authors.lastname: Wong
authors.affiliation: Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Alberta T2N 4Z6, Canada nisyed@ucalgary.ca.
authors.forename: Naweed I
authors.initials: NI
authors.lastname: Syed
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017952:Ganglia, Invertebrate / Q000166:cytology; D005730:Ganglionic Blockers / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology; D006835:Hydrazones / Q000494:pharmacology; D008195:Lymnaea / Q000166:cytology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000378:metabolism; D013569:Synapses / Q000145:classification* / Q000187:drug effects / Q000502:physiology*; D055366:Synaptic Potentials / Q000187:drug effects / Q000502:physiology
chemical_list: D053119:Benzophenanthridines; D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D005730:Ganglionic Blockers; D006835:Hydrazones; C511794:N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide; D011978:Receptors, Nicotinic; D018738:Hexamethonium; C016299:chelerythrine; D000109:Acetylcholine
keywords: axons; chemical synapses; electrical synapses; somata; synapse formation; trophic factors