New Molecular Insights into How Neurons Communicate During Learning; Synaptic Nanomodules Underlie Organization & Plasticity of Spine Synapses

(BY RACHEL DERITA, PhD Candidate,Thomas Jefferson University, Department of Cancer Biology) The laboratory of Matthew Dalva, PhD, and Director of the Synaptic Biology Center at Thomas Jefferson University in Philadelphia, has gained new insight into how synapses change upon learning in the brain. These findings come from a study published in Nature Neuroscience on April 23, 2018. The article is titled : Synaptic Nanomodules Underlie the Organization and Plasticity of Spine Synapses.” It was already known that upon learning, connections between neurons strengthen and become bigger. But this new study showed specifically that molecules involved in transmitting signals between neurons organize in clumps called “nanomodules” that dance and multiply when neurons are stimulated by signals that mimic learning. Super-resolution live-cell microscopy was used to show this dynamic behavior of molecules during neuronal communication on a cellular and molecular level by zooming into synapses in real-time. When further analyzing the behavior of these nanomodules, it was discovered that key molecules on the pre-synaptic side (such as vesicular glutamate transporter; VGLUT) not only clustered, but lined up and tracked with the post-synaptic proteins (such as post-synaptic density protein 95; PSD-95). When stimulated with signals to strengthen the synaptic connection between two neurons, a stationary nanomodule would begin to move around the synaptic spine, and the pre- and post-synaptic components would still track with each other. The nanomodules also had a uniform size and multiplied when the neurons were stimulated to grow and nearly touch each other across the synapse. The number of nanomodules was positively correlated with the size of the spines.
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