Webinar Review: Alternative splicing choices for synaptic function

Our trainees review webinars in their given fields and share abstracts to help colleagues outside their discipline make an informed choice about watching them. As our program bridges diverse disciplines, these abstracts are beneficial for our own group in helping one another gain key knowledge in each other’s fields. We are happy to share these here for anyone else who may find them helpful.

Alternative splicing choices for synaptic function

Andrea Gomez, PhD, Assistant Professor in the Department of Molecular and Cell Biology and the Helen Wills Neuroscience Institute at the University of California, Berkeley


Allen Institute

Jennifer WaltersAnalysis by Jennifer Walters:

This talk was given by Dr. Gomez as part of the Allen Institute’s Distinguished seminar series and elaborates on the potential of alternative RNA splicing to expand the coding power of the genome, as well as the potential of this splicing to fine-tune molecular complexity for selective circuit function. Dr. Gomez’s lab specifically discovered an RNA-binding protein called Slm2, which drives a highly dedicated alternative splicing program that targets a splice segment specific to synaptic adhesion molecules. Specifically, Slm2 targets the splicing of Neurexins, which mediate cell-to-cell interactions and are key for synapse formation and maintenance (e.g., synaptic pruning). Slm2 generates isoforms that are essential for glutamatergic synapse specification within the hippocampus (a region of the brain critical for learning and memory formation/processing).

Ultimately, her lab’s research has found that alternative splicing is a critical mechanism for neurons to generate and control the large variability seen in its synaptic function, where her lab looks specifically at CA1-CA3 neuronal synapse activity. She notes that the highest form of alternative splicing occurs in neurons compared to other cell types within the body, which is fascinating and yet makes sense. This is quite significant in terms of finding ways to clinically treat neurological disorders, considering small changes to synaptic properties are predicted to have large effects on the information flow to an activated, engaged neuron. I am personally interested to see how this area develops in terms of targeting treatment and/or future drug development.

Gomez goes on to discuss the future directions and current projects of her lab; one approach that I found intriguing is her project investigating the RNA biology of psychedelics. She is focused on gaining insight into “opening plasticity windows into the brain” in order to discover novel plasticity RNAs and understand how they coordinate large-scale neural plasticity. She makes the point that in neurological disorders, our ability to learn, remember, recover from trauma, etc., is limited not by will, but by our neuronal capacity to synthesize components crucial for cognitive flexibility. Un-tapping the brain’s potential in this area may help us move towards alternative ways of healing that mimic the effects of psychedelics.

Overall, I thought the presentation of this webinar was fantastic. Dr. Gomez’s speech and cadence was fluid and concise, she presented her research in a logical manner, and the slides were not overrun with text. One thing that I deeply appreciated personally about her talk was that she emphasized and elaborated on each image within her presentation carefully – I’ve watched many presentations where images are thrown onto slides without much rhyme or reason, or they are barely touched on even though they are supposed to provide the audience with critical foundational background about the project/protein/method/etc. being discussed. I think that this talk was perfect for anyone with a background in neuroscience (specifically neuronal plasticity), but I feel it could be comprehended by someone with a basic molecular background as well.