ESTABLISHING NON-INVASIVE; HIGH-RESOLUTION RECORDINGS IN THE TOP-DOWN LAYER OF NEOCORTEX
Relevant for Research Area
B - Core Technologies
Prof. Dr. Johannes Letzkus
Prof. Dr. Thomas Stieglitz
Mounting evidence identifies the top-most layer of sensory neocortex (L1) as a highly specializedsite in terms of organization and in vivo function. A string of recent studies, many by the Letzkuslab, has revealed that L1 overwhelmingly encodes top-down information related to the pastexperiences and present objectives of an individual (Letzkus et al., 2015; Abs et al., 2018;Poorthuis et al., 2018; Pardi et al., 2020; Hartung and Letzkus, 2021). Compared to the intenselyinvestigated processing of bottom-up sensory inputs, we yet know very little about these top-downsignals. This information is crucial for a mechanistic understanding of higher brain functions likememory, and is moreover likely exploitable for optimizing voluntary control of brain-machineinterfaces. However, a key bottleneck constraining progress on these issues is the current lack ofappropriate technology for high resolution recordings from layer 1, the present gold standard being2-photon calcium imaging with inferior temporal resolution and sensitivity. While large-scaleextracellular recordings can overcome these shortcomings, conventional approaches usingpenetrating depth electrodes are unable to record from layer 1 due to its location and the sparsityof neurons there. Here, our objective is to synergize the strong and long-standing expertise of theStieglitz lab in design and fabrication of innovative probes for electrical recordings with the ongoingresearch program on layer 1 in the Letzkus lab to establish non-invasive, high-resolutionrecordings from this unique site. To this end, we will combine mouse lines generated by Letzkusthat selectively target layer 1 interneurons (Abs et al., 2018) with conformable surface gridelectrode arrays. These micromachined polyimide-based arrays with integrated electrode sites fora conformable interface (Rubehn et al., 2009; Vomero et al., 2020) are able to record both localfield potentials (Bosman et al., 2012; Delfino et al., 2021) as well as spike-like activity (Galindo-Leon et al., 2019). Designs will be optimized with respect to electrode size and arrangement aswell as coating material and surface texture based on the anatomy of the target structure and theoptogenetic methodology. Combined with optogenetic control over layer 1 interneuron activity, thisproject is in an excellent position to make rapid progress on this important technological innovation. Neuroscientific findings will be complemented by knowledge generation on reactions at the implant-tissue interface, for example on biofouling (protein adsorption) due to surface texture modifications.