New views on cleared tissue and live dendrites

In my presentation, I like to show news on two topics. First, we are developing new microscopy tools for visualizing large-scale neural circuits in cleared brain tissue. A few years ago, we launched the mesoSPIM initiative, which disseminates open-source light-sheet microscopes that are highly suitable for imaging cleared mouse brains. We now published the next-generation ‘Benchtop mesoSPIM’, a more compact and improved version. I will present the special features and advantages of this new instrument. In addition, we have come up with an entirely new concept of microscope objectives for imaging large, cleared samples (the “Schmidt objective”). Inspired by telescopes from astronomy, we put together a spherical mirror and an aspheric correction plate to form a powerful objective design for high-resolution two-photon imaging of cleared specimen. The unique feature of this new design is that it performs well with any immersion medium, from air to oils with high refractive index. Finally, I like to touch upon our recent in vivo studies of dendritic dynamics in the neocortex during learning. Based on our experimental data we have developed a reinforcement learning model, in which certain types of errors can be matched to the dendritic changes that we observe in mice when they learn a new discrimination task. I will explain our model that could be useful to generate further specific hypotheses and that might provide a handle to more closely link neuronal dynamics to mathematical terms in learning theories.


As an experimental neuroscientist with physics background my general research interest is to reveal principles of neural computation on the cellular and network level using electrophysiology and particularly optical methods. My lab has majorly contributed to advances in the field of two-photon microscopy for in vivo studies of neuronal circuit dynamics and glial function. Notable past achievements include (i) the quantitative analysis of Ca2+ signaling in dendrites and presynaptic terminals of neurons; (ii) the characterization of dendritic Ca2+ signaling in neocortical pyramidal cells in vivo using two-photon microscopy; (iii) the pioneering work of developing a miniaturized two-photon microscope for high-resolution imaging in freely moving rodents; (iv) the discovery of a specific label for astrocytes in vivo; (v) the seminal discovery of high resting motility of microglial cells in vivo; (vi) the development of novel laser scanning techniques for volumetric and high-speed measurements from large populations of cells in the neocortex; and most recently (vi) the application of genetically-encoded calcium indicators for longitudinal imaging studies in awake, behaving mice to reveal neocortical dynamics underlying short-term memory and learning. In recent years, my lab has expanded towards various brain regions, including hippocampus and thalamus, using new microscopy concepts, genetically encoded sensors, and optogenetic and chemogenetic tools to monitor and manipulate specific cellular circuit components. Our goal is to gain a mechanistic understanding of signal flow on the mesoscale, taking into account local microcircuit operation as well as principles of large-scale brain dynamics.