Dr. Kristen Harris and her lab have made great strides in the field of structural basis of synaptic plasticity using physiology and electron microscopy image reconstruction. In this study this lab began to explore the structure of nascent and active synapses and the mechanism behind the synaptic plasticity of recruiting these nascent synapses. It has been shown that nascent synapses lay on the outskirts of active synapses and serve as highly dynamic regions for AMPA receptor activity. Even with this receptor traffic though, these nascent synapses lack neurotransmitter vesicles and therefore stay dormant. What has not been studied is if Dense Core Vesicles (DCVs) are trafficked to these nascent synapses under Long term potentiation (LTP) conditions. DCVs are know to transport presynaptic scaffolding and many proteins necessary for vesicle docking as well as cell adhesion proteins.
In order to explore this further, the Harris lab stimulated with a Theta-burst stimulation and recorded from rat hippocampal slices in the CA1. They fixed tissue after 5min, 30min, and 2hrs. They used 3D electron microscopy (EM), EM tomography, and image reconstruction to study the structural changes in these slices. The first thing that they did was to characterize active and nascent synapses and their vesicles through EM imaging. They observed that synapses that did have nascent zones most likely had them on the outside of the active zones. Also, they show that under LTP conditions active zones undergo a larger area expansion then those without nascent zones. This begins to show nascent zone influence on active zones in the synapse. They finish by showing that more DCVs traffic to nascent zones with LTP stimulation. This in turn promotes an increase in the minimum distance necessary between docked vesicles and nascent zones for these nascent zones to be converted into active zones, as shown in the figure. This study offers a window into the mechanisms behind synaptic plasticity and illuminates some of the structural mysteries behind synaptic efficacy.
To learn more about Dr. Harris’s research, please attend her talk on Tuesday, May 16, 2017 at 4pm in the CNCB Marilyn G. Farquhar Seminar Room.
Kevin White is a PhD student currently rotating in Dr. Axel Nimmerjan’s lab in the Biophontonics Center at the Salk Institute.