title: Trophic factor-induced activity 'signature' regulates the functional expression of postsynaptic excitatory acetylcholine receptors required for synaptogenesis.
abstract: Highly coordinated and coincidental patterns of activity-dependent mechanisms ("fire together wire together") are thought to serve as inductive signals during synaptogenesis, enabling neuronal pairing between specific sub-sets of excitatory partners. However, neither the nature of activity triggers, nor the "activity signature" of long-term neuronal firing in developing/regenerating neurons have yet been fully defined. Using a highly tractable model system comprising of identified cholinergic neurons from Lymnaea, we have discovered that intrinsic trophic factors present in the Lymnaea brain-conditioned medium (CM) act as a natural trigger for activity patterns in post- but not the presynaptic neuron. Using microelectrode array recordings, we demonstrate that trophic factors trigger stereotypical activity patterns that include changes in frequency, activity and variance. These parameters were reliable indicators of whether a neuron expressed functional excitatory or inhibitory nAChRs and synapse formation. Surprisingly, we found that the post- but not the presynaptic cell exhibits these changes in activity patterns, and that the functional expression of excitatory nAChRs required neuronal somata, de novo protein synthesis and voltage gated calcium channels. In summary, our data provides novel insights into trophic factor mediated actions on neuronal activity and its specific regulation of nAChR expression.
authors.affiliation: Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Alberta, Canada.
authors.forename: Collin C
authors.initials: CC
authors.lastname: Luk
authors.affiliation: Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Alberta, Canada.
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Lee
authors.affiliation: Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Alberta, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Wijdenes
authors.affiliation: Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Alberta, Canada.
authors.forename: Wali
authors.initials: W
authors.lastname: Zaidi
authors.affiliation: Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Alberta, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Leung
authors.affiliation: Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Alberta, Canada.
authors.forename: Noelle Y
authors.initials: NY
authors.lastname: Wong
authors.affiliation: Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Alberta, Canada.
authors.forename: Joseph
authors.initials: J
authors.lastname: Andrews
authors.affiliation: Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Alberta, Canada.
authors.forename: Naweed I
authors.initials: NI
authors.lastname: Syed
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials; D008195:Lymnaea; D055495:Neurogenesis; D009474:Neurons / Q000502:physiology; D010641:Phenotype; D014176:Protein Biosynthesis; D011950:Receptors, Cholinergic / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*; D013997:Time Factors
chemical_list: D015220:Calcium Channels; D011950:Receptors, Cholinergic
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