Abstract
During the development of the nervous system, synaptogenesis occurs in excess though only the appropriate connections consolidate. At the neuromuscular junction, competition between several motor nerve terminals results in the maturation of a single axon and the elimination of the others. The activity-dependent release of transmitter, cotransmitters, and neurotrophic factors allows the direct mutual influence between motor axon terminals through receptors such as presynaptic muscarinic ACh autoreceptors and the tropomyosin-related kinase B neurotrophin receptor. In previous studies, we investigated the synergistic and antagonistic relations between these receptors and their downstream coupling to PKA and PKC pathways and observed a metabotropic receptor-driven balance between PKA (stabilizes multinnervation) and PKC (promotes developmental axonal loss). However, how much does each kinase contribute in the developmental synapse elimination process? A detailed statistical analysis of the differences between the PKA and PKC effects in the synapse elimination could help to explore this point. The present short communication provides this analysis and results show that a similar level of PKA inhibition and PKC potentiation would be required during development to promote synapse loss.
Highlights
The phosphorylation of pre- and postsynaptic protein kinase A (PKA) and protein kinase C (PKC) targets involved in transmitter release and nerve terminal and/or nicotinic ACh receptors (nAChR) stability could realize the final molecular mechanism of synapse loss
To further know the PKA and PKC action on this mechanism, we ask several questions that can be answered by comparing PKA and PKC effects on the nerve terminal loss and nAChRs cluster maturation: What can be the relative contribution of each kinase in developmental synapse elimination? What is more determinant to final synapse elimination: PKA inhibition or PKC activation? A detailed statistical analysis of the differences between the PKA and PKC effects in the synapse elimination process will help to explore these crucial points and encourage more specific experiments
We compared synaptic maturation) and we found no difference in either number of axons per synapse synaptic maturation) and we found no difference in either number of axons per synapse or or the in the morphological postsynaptic maturation(in
Summary
The present short communication highlights details on the statistical analysis of the differences between the PKA and PKC effects on axonal competition and the synapse loss process. In the forementioned paper [9], we described that PKA-I and II activity seems to stabilize multiinervation by delaying both axonal elimination and postsynaptic nicotinic ACh receptors (nAChR) pretzel-like cluster differentiation in P5-P9 neonatal mice. Activity promotes both developmental axon loss (through cPKCβI and nPKCε isoform action) and postsynaptic nAChR cluster maturation (a possible role for PKCθ).
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