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Researchers Find a “Digital” Mechanism Behind Neuronal Changes from Learning

Neurons react to learning and memory by activating synaptic connections. The mechanisms behind this fundamental process are complex and poorly understood. Researchers at Thomas Jefferson University have found that neuron plasticity operates in a “digital” fashion through nanomodules of discrete size that multiply and strengthen neuronal connections upon stimulation. This breakthrough was published on April 23rd in the journal Nature Neuroscience.

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A critical aspect to consider when imaging neuron spines is their size, well below the diffraction limit of visible light. Far-field fluorescence Nanoscopy enables the elucidation of such details with nanometer resolution and molecular specificity. Using multicolor STED Nanoscopy to investigate live cells, the team, lead by Dr. Dalva, labeled and tracked proteins responsible for signal transmission in pre- and post-synaptic regions. They identified protein clusters, involved in both the sending and receiving of signals, that reached the neuron spines upon stimulation. These clusters, termed nanomodules, were homogeneous in size and aligned from the pre- to the post-synaptic regions as if they were coordinated. 

Surprisingly, they observed that the nanomodules multiplied in number, but not in size, upon stimulation. This result suggests that a “digital” mechanism is operating, where greater synapse strength depends upon an adding up of discrete units of the same size and not simply a continuous increase in the number of recruited proteins. Adding to this breakthrough, the researchers also found that, upon stimulation, the nanomodules began jiggling and moving, while the pre- and post-synaptic components remained locked in place. 

These findings open the door to further investigations into the role of nanomodules in neuron plasticity. How these clusters assemble, align, and link the pre- and post-synaptic regions, as well as why they jiggle upon stimulation, are only some of the key questions to be addressed. Providing answers will help improve understanding of the molecular based mechanisms involved in learning, memory, and, ultimately, fighting against neurological disorders.

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Hruska M, Henderson N, Le Marchand SJ, Jafri H & Dalva MB:

Synaptic nanomodules underlie the organization and plasticity of spine synapses

Nature Neuroscience 21, pages671–682 (2018)doi:10.1038/s41593-018-0138-9