A STED Microscope for Multimodal Investigation of Dendritic Spine Structure and Function

Elucidating the relationship between the morphology of dendritic spines and the function of the synapses they harbor is crucial for understanding how neuronal networks process and store information. Activity-dependent changes in synapse function and spine morphology are tightly regulated and mutually dependent. Due to the complex and dynamic nature of these small structures, investigating their dynamics poses significant technical challenges. Here, we describe an advanced combination of approaches to investigate spine-synapse dynamics in mouse brain slices. Specifically, we present a home-built setup that incorporates time-lapse stimulated emission depletion microscopy, two-photon glutamate uncaging, patch-clamp electrophysiology, and calcium imaging. We outline an integrative approach to investigate the interplay between synapse function and spine morphology, and ultimately shed light on the fundamental processes underlying neural communication and plasticity in brain slices.