Whole-brain recording into nucleic acids using template-independent polymerases

The objective of this proposal is to record that information locally (in the cell) in an information dense recording substrate (DNA/RNA) using a genetically-encodable recorder (DNA/RNA polymerase). Recording into DNA sidesteps the need to extract the data in realtime and genetically encoded recorders could cover the entire brain without invasive probes with single cell resolution. Furthermore, DNA/RNA polymerases can incorporate bases quickly and with many parallel recordings in the cell, sub-second time resolution is possible. Recently, the Tyo and Boyden labs have demonstrated a unique class of polymerases that do not require templates for base addition incorporate specific bases associated with Ca2+ over time into DNA/RNA.