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Seeing into the Synapse: an eye-opening discussion

Jayalakshmi Viswanathan

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Jayalakshmi Viswanathan

Dr. Matthew Dalva is the Presidential Chair, Director of the Tulane Brain Institute and Professor of Cell and Molecular Biology. His research is focused on synapses biology. His lecture Seeing into the Synapse was an introduction to the study of synapses – how they form, how they are maintained, and what are the factors that affect their attributes (such as size and strength).

One fascinating aspect of synapses is that they are quite sparse. While a single dendritic spine (protrusions from dendrites at the end of which synapses may form) may touch about 12 different axons, only one forms the synapse. To investigate questions like how decisions about synapse formation and maintenance are executed at the molecular and nano scales, Dr. Dalva discussed a series of experiments. The role of ephBs and ephrinBs (found in dendritic filopodia) in synapse formation was highlighted using knock-out animal models resulting in 40% fewer spine synapses, and the restoration of these proteins rescued synapse formation. Subsequent modeling of the role of EphB signaling demonstrated that while rapid photoactivation of this protein results in the retraction of filopodia to seek new targets, slow and sustained activation of this protein triggers synapse formation indicating that the rate of activation is the key to determining synapse formation.

Next, Dr. Dalva discussed elements of structural features of a synapse and using super-resolution synaptic imaging shed light on the nano-scale order within synapses. The beautiful images of the synapses and quantification of these revealed nanocolumns of clustered proteins which determine synaptic strength/integrity – there was a correlation between number of the nanoscale column structures and size of the spine. Further investigation from his lab revealed that physical processes like liquid-liquid phase separation can play an important role in how proteins cluster to form these nanocolumns and determine synapse strength, both at the pre-synaptic and post-synaptic sites.       

As a neuroscientist and a neuroartist, I was very excited to tune in to this SfN webinar in March 2024. The title drew me in on multiple levels, the primary being curiosity to understand the synapse, the point of connection between neurons that forms the building blocks of all the amazing feats of nervous systems. I was also hoping for beautiful images of neuroart, and this lecture did not disappoint on any level. The lecture spanned many aspects of synapse biology – protein-protein interaction, structure-function relationships, biophysics, temporality of synapse formation, etc., and the rich discussions during the Q&A further expanded it. The discussion covered topics related to how synapse elements might be changing and how they can be measured during development, aging, disease, etc., as well as how these nanoscale elements might generalize across type of neurons (excitatory vs inhibitory). I would recommend this lecture to all neuroscientists with an interest in synapse biology.

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