Wnt signaling mediates experience-related regulation of synapse numbers and mossy fiber connectivities in the adult hippocampus.
We investigated how experience regulates the structure of a defined neuronal circuit in adult mice. Enriched environment (EE) produced a robust and reversible increase in hippocampal stratum lucidum synapse numbers, mossy fiber terminal (LMT) numbers, and spine plus synapse densities at LMTs, whereas a distinct mechanism depending on Rab3a promoted LMT volume growth. In parallel, EE increased postsynaptic CA3 pyramidal neuron Wnt7a/b levels. Inhibiting Wnt signaling through locally applied sFRP-1 suppressed the effects of EE on synapse numbers and further reduced synapse numbers in control mice. Wnt7 applied to CA3 mimicked the effects of EE on synapse and LMT numbers. CA3 Wnt7a/b levels were enhanced by excitatory activity and reduced by sFRP-1. Synapse numbers and Wnt7a/b levels peaked in mice aged 6-12 months; a decline in aged mice was reversed by EE. Therefore, behavioral experience specifically regulates adult global stratum lucidum synapse numbers and hippocampal network structure through Wnt signaling.
Gogolla
Nadine
N
Friedrich Miescher Institut, CH-4058 Basel, Switzerland.
Galimberti
Ivan
I
Deguchi
Yuichi
Y
Caroni
Pico
P
D000367:Age Factors; D000818:Animals; D004777:Environment; D027261:Fusion Regulatory Protein-1 / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D019599:Mossy Fibers, Hippocampal / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D018800:Thy-1 Antigens / Q000235:genetics; D015854:Up-Regulation / Q000502:physiology; D051153:Wnt Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D020826:rab3A GTP-Binding Protein / Q000172:deficiency
D027261:Fusion Regulatory Protein-1; D012269:Ribosomal Proteins; D018800:Thy-1 Antigens; D051153:Wnt Proteins; C027937:ribosomal protein L16; C060232:ribosomal protein L21; D049452:Green Fluorescent Proteins; D020826:rab3A GTP-Binding Protein