TY - JOUR
T1 - Specificity of synapse formation in Aplysia
T2 - paracrine and autocrine signaling regulates bidirectional molecular interactions between sensory and non-target motor neurons
AU - Alexandrescu, Anamaria
AU - Carew, Thomas James
N1 - Funding Information:
The formation of specific neural connections is critical for the proper development and function of the nervous system. Specificity of synapse formation is supported by complex bidirectional intercellular and intracellular signaling between and within potential pre-and postsynaptic partners1. The molecules mediating these intercellular exchanges, including growth factors, neuropeptides, neurotransmitters, and cell adhesion molecules, activate intracellular signaling cascades leading to functional and structural changes that promote the formation of functional synapses1–5. The synaptic proteins supporting the morphological changes that mediate the formation, restructuring, and elimination of synapses have been extensively studied1,5. However, the extracellular factors and the intracellular signal transduction pathways that regulate the expression of the genes encoding proteins required for appropriate synaptic connectivity remain largely unknown.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - The formation of appropriate neural connections during development is critical for the proper wiring and functioning of the brain. Although considerable research suggests that the specificity of synapse formation is supported by complex intercellular signaling between potential presynaptic and postsynaptic partners, the extracellular factors and the intracellular signal transduction pathways engaged in this process remain largely unknown. Using the sensory-motor neural circuit that contributes to learning in defensive withdrawal reflexes in Aplysia californica, we investigated the molecular processes governing the interactions between sensory neurons and both target and non-target motor neurons during synapse formation in culture. We found that evolutionarily-conserved intercellular and intracellular signaling mechanisms critical for learning-related plasticity are also engaged during synaptogenesis in this in vitro model system. Our results reveal a surprising bidirectional regulation of molecular signaling between sensory neurons and non-target motor neurons. This regulation is mediated by signaling via both paracrine and autocrine diffusible factors that induce differential effects on transcription and on protein expression/activation in sensory neurons and in target and non-target motor neurons. Collectively, our data reveal novel molecular mechanisms that could underlie the repression of inappropriate synapse formation, and suggest mechanistic similarities between developmental and learning-related plasticity.
AB - The formation of appropriate neural connections during development is critical for the proper wiring and functioning of the brain. Although considerable research suggests that the specificity of synapse formation is supported by complex intercellular signaling between potential presynaptic and postsynaptic partners, the extracellular factors and the intracellular signal transduction pathways engaged in this process remain largely unknown. Using the sensory-motor neural circuit that contributes to learning in defensive withdrawal reflexes in Aplysia californica, we investigated the molecular processes governing the interactions between sensory neurons and both target and non-target motor neurons during synapse formation in culture. We found that evolutionarily-conserved intercellular and intracellular signaling mechanisms critical for learning-related plasticity are also engaged during synaptogenesis in this in vitro model system. Our results reveal a surprising bidirectional regulation of molecular signaling between sensory neurons and non-target motor neurons. This regulation is mediated by signaling via both paracrine and autocrine diffusible factors that induce differential effects on transcription and on protein expression/activation in sensory neurons and in target and non-target motor neurons. Collectively, our data reveal novel molecular mechanisms that could underlie the repression of inappropriate synapse formation, and suggest mechanistic similarities between developmental and learning-related plasticity.
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U2 - 10.1038/s41598-020-62099-4
DO - 10.1038/s41598-020-62099-4
M3 - Article
C2 - 32251363
AN - SCOPUS:85082517545
SN - 2045-2322
VL - 10
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 5222
ER -