Development of molecular tools for manipulating and studying memory engrams

The C01 project provides customized optogenetic, viral and transcriptome analysis tools to investigate the mechanisms of memory consolidation. We will support other projects by extensive consultation and knowledge transfer, and develop novel tools specifically designed to enable state-of-the-art memory research. In the area of optogenetics we will tailor recently published actuators and sensors for project-specific implementations and develop new optogenetic tools for photocontrol of intracellular signaling cascades involving Ca2+, cAMP and G-protein signaling, enabling novel avenues for modulating cellular memory formation. For optimized viral gene transfer and circuit analysis, we improve existing retrograde tracers by reducing cytotoxicity and develop novel, herpesvirus-based tracers that promise efficient low toxicity anterograde trans-synaptic tracing for neuronal circuit analysis. Finally, we provide support for applying PatchSeq, DropSeq, and 10xVisum single cell omics platforms to identify cellular components of memory engrams and to investigate which gene expression patterns contribute to the formation of these engrams. Our work will also be beneficial for the neuroscience community outside the CRC as we make our tools available worldwide through DNA repositories and our viral core facility.

Image Schematic overview of the three work packages of the C01 project – optogenetics, viral tools, and transcriptome readouts. Image by Thorsten Trimbuch, Johannes Vierock, Benjamin Rost.

Archive – C01 (SFB1315/1)

Graphical Abstract: WP1 will customize and validate existing optogenetic tools and develop two new classes of optogenetic actuators that allow for light-gated Ca2+ influx while avoiding strong membrane depolarization, and optical bidirectional control of intracellular G-proteins and 2nd messengers. WP2 will develop viral systems for anterograde and retrograde trans-synaptic tracing for neuronal circuit analysis. WP3 will provide analytical tools for deciphering the transcriptional landscape of single cells at high-resolution. Collaborations for the WPs are indicated on the right.