IVSTED · In vivo super-resolution imaging of synapses in the hippocampus

In vivo super-resolution imaging of synapses in the hippocampus

The hippocampus is a deeply embedded region in the mammalian brain that has long been considered the archetypical center for memory formation. Hippocampal neurons process information by integrating a vast number of synaptic inputs via dendritic spines. These postsynaptic structures are highly dynamic and their plasticity is hypothesized to be important structural correlate of the memory trace. However, due to their nanometric size and high density, it is extremely challenging to study the function of dendritic spines under realistic experimental conditions. Indeed, conventional light microscopy fails to properly resolve their fine morphological details, while electron microscopy only provides snapshots from fixed brain sections. Therefore, our view of spine dynamics remains very incomplete, limiting our understanding of the synaptic mechanisms underlying brain physiology and animal behavior. Leveraging recent developments in optical super-resolution microscopy, adaptive optics and mouse brain surgery techniques, the objective of this project was to establish an innovative approach for nanoscale imaging of hippocampal spines in living mice during memory acquisition and recall. Using this approach, the aim was to perform chronic imaging over several weeks in a cohort of animals to investigate the dynamics of hippocampal spines in vivo with unprecedent spatial resolution, focusing on their turnover and nanoscale morphology during behavioral tests of the capacity of mice to learn and remember things. Specifically, my project focused on tackling the following three main objectives: (1) Develop adaptive optics-based 3D super-resolution microscopy to improve image resolution and penetration, (2) Establish chronic in vivo super-resolution imaging to determine spine morphology and turnover over the course of weeks in live animals, (3) Investigate how spine plasticity correlates with memory performance in the same animal. Due to my recruitment as a permanent researcher I had to end up this Marie Slodowska Curie action project after only seven months. Therefore, this project is far from being finished. However, in the context of my new position I will largely continue working on the thematic. Indeed, in the context of the IVSTED project I was able to establish the foundation of my project first by implementing the adaptive optics setup necessary to improve image resolution in depth and secondly by successfully establishing the surgery protocol to implant hippocampal cranial window, which is an important milestone for the success of this project.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз