Novel targeting strategies for multi-population voltage imaging

The dynamic interplay between multiple distinct excitatory and inhibitory cell types lies at the core of information processing in animal perception and behavior. To study how distinct neuron types interact in real-time, mutually compatible optical tools are needed to enable concurrent recordings from multiple targeted subtypes. While spectrally separable indicators (e.g., green and red indicators) are optically compatible for multiplexing, other orthogonal properties among indicators, such as opposite response polarities, present newer means of unmixing optical signals from identified cell types. For improved multiplexing capabilities, we will:

• engineer novel indicators with non-overlapping emission spectra, opposite response polarities, or other tangential response properties,

• develop targeting strategies for non-overlapping expression of compatible indicators in distinct neuron types, and

• validate their mutual compatibility for simultaneous multipopulation imaging in behaving animals.