title: Synapse number and synaptic efficacy are regulated by presynaptic cAMP and protein kinase A.
abstract: The mechanisms by which neurons regulate the number and strength of synapses during development and synaptic plasticity have not yet been defined fully. This lack of fundamental knowledge in the fields of neurodevelopment and synaptic plasticity can be attributed, in part, to compensatory mechanisms by which neurons accommodate for the loss of function in their synaptic partners. This is generally achieved either by scaling up neuronal transmitter release capabilities or by enhancing the postsynaptic responsiveness. Here, we demonstrate that regulation of synaptic strength and number between identified Lymnaea neurons visceral dorsal 4 (VD4, the presynaptic cell) and left pedal dorsal 1 (LPeD1, the postsynaptic cell) requires presynaptic activation of a cAMP-PKA-dependent signal. Experimental activation of the cAMP-PKA pathway resulted in reduced synaptic efficacy, whereas inhibition of the cAMP-PKA cascade permitted hyperinnervation and an overall enhancement of synaptic strength. Because synaptic transmission between VD4 and LPeD1 does not require a cAMP-PKA pathway, our data show that these messengers may play a novel role in regulating the synaptic efficacy during early synaptogenesis and plasticity.
authors.affiliation: Respiratory Research Group, Faculty of Medicine, University of Calgary, Calgary, Alberta, T2N 4N1 Canada.
authors.forename: David W
authors.initials: DW
authors.lastname: Munno
authors.forename: David J
authors.initials: DJ
authors.lastname: Prince
authors.forename: Naweed I
authors.initials: NI
authors.lastname: Syed
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology; D002450:Cell Communication / Q000502:physiology; D002469:Cell Separation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D007546:Isoquinolines / Q000494:pharmacology; D017774:Long-Term Potentiation; D008195:Lymnaea; D009414:Nerve Growth Factors / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D018377:Neurotransmitter Agents / Q000502:physiology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D013449:Sulfonamides; D013569:Synapses / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D017077:Culture Media, Conditioned; D007546:Isoquinolines; D009414:Nerve Growth Factors; D018377:Neurotransmitter Agents; D013449:Sulfonamides; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide