All-trans retinoic acid induces synaptic plasticity in human cortical neurons

A defining feature of the brain is the ability of its synaptic contacts to adapt structurally and functionally in an experience-dependent manner. In the human cortex, however, direct experimental evidence for coordinated structural and functional synaptic adaptation is currently lacking. Here, we probed synaptic plasticity in human cortical slices using the vitamin A derivative all-trans retinoic acid (atRA), a putative treatment for neuropsychiatric disorders such as Alzheimer's disease. Our experiments demonstrated that the excitatory synapses of superficial (layer 2/3) pyramidal neurons underwent coordinated structural and functional changes in the presence of atRA. These synaptic adaptations were accompanied by ultrastructural remodeling of the calcium-storing spine apparatus organelle and required mRNA translation. It was not observed in synaptopodin-deficient mice, which lack spine apparatus organelles. We conclude that atRA is a potent mediator of synaptic plasticity in the adult human cortex.

Automated summary

A defining feature of the brain is its ability for synaptic contacts to adapt structurally and functionally, with atRA being identified as a potent mediator of synaptic plasticity in the adult human cortex. The coordinated structural and functional changes in excitatory synapses observed in cortical slices were accompanied by ultrastructural remodeling of the spine apparatus organelle and required mRNA translation for these synaptic adaptations. The absence of these changes in synaptopodin-deficient mice suggests the importance of this organelle in the process.