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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. When it comes to synaptic strength, the changes “might be more digital than analog-with same sized units added to change synaptic strength,” commented Dr. Dalva.

There are many questions raised by these new observations about molecular behavior during synaptic neuronal communication. It is still unknown how and why these nanomodules appear to have a uniform size, and exactly how and why they multiply and move during synaptic stimulation. There is also the question of how the pre- and post-synaptic nanomodules move in lock step with each other.

However, the most important question to come from this study involves whether or not there are crucial changes to these nanomodules and their behavior in different states such as addiction or in neurological disorders such as autism. This study provides a platform and methodology with which to study this question and potentially gain valuable insight into the mechanisms of neurological disorders.

IMAGE

Image shows synaptic spines (yellow outline) showing nanomodules on pre-(pink) and postsynaptic (blue) sides of neurons.

[Press release] [Nature Neuroscience abstract]