Development of molecular tools for manipulating and studying memory engrams

Over the last decade the number, variety and specificity of optical and genetic tools that report or modify neural activity, such as calcium and voltage sensors or light-gated channels and light driven pumps, has increased exponentially. Many if not most laboratories now use genetically encoded tools to address research questions, however the accessibility of these tools remains limited. In this CRC, we will offer custom tailored viral vector based tools optimized for investigation of the mechanisms underlying memory consolidation. The choice of tools will take into account two main parameters: spatial confinement of such tools (i.e. the neurons and circuits involved), and their biophysical properties to match the experimental condition and the biology of memory consolidation. These tools have recently advanced beyond simple manipulation and now allow researchers within the CRC to manipulate, investigate or reconstruct neural circuits. How memory circuits are consolidated can also be studied by examining gene expression in the participating neurons. Correlating gene expression with connectivity patterns can be particularly useful in describing underlying mechanisms of memory formation, as well as providing anatomical markers for neurons participating in the memory engrams. This can be accomplished through the use of transcriptome analysis by means of single cell RNA sequencing.

Knowhow in molecular biology, cell biology, physiology and bioinformatics are required to develop the above tools, as well as analyzing and understanding the outcome of their use. The C01 project will serve as a hub for research in design and production of tools in order to support circuit analysis on morphological, molecular and functional levels.

Image CA1 hippocampal formation infected with pAAV-Syn-FLEX-Ce3ToG-WPRE3 (Cerulean, TVA receptor, Glycoprotein G) and with the Rabies virus pRVdG-N-P-M-EGFP-SynPhRFP-L (expressing green fluorescent protein and Synaptophysin-RFP). Courtesy of Dr. Julie Ledderose (AG Larkum)