PT - JOURNAL ARTICLE AU - Samouil L. Farhi AU - Vicente J. Parot AU - Abhinav Grama AU - Masahito Yamagata AU - Ahmed S. Abdelfattah AU - Yoav Adam AU - Shan Lou AU - Jeong Jun Kim AU - Robert E. Campbell AU - David D. Cox AU - Adam E. Cohen TI - Wide-Area All-Optical Neurophysiology in Acute Brain Slices AID - 10.1523/JNEUROSCI.0168-19.2019 DP - 2019 Jun 19 TA - The Journal of Neuroscience PG - 4889--4908 VI - 39 IP - 25 4099 - http://www.jneurosci.org/content/39/25/4889.short 4100 - http://www.jneurosci.org/content/39/25/4889.full SO - J. Neurosci.2019 Jun 19; 39 AB - Optical tools for simultaneous perturbation and measurement of neural activity open the possibility of mapping neural function over wide areas of brain tissue. However, spectral overlap of actuators and reporters presents a challenge for their simultaneous use, and optical scattering and out-of-focus fluorescence in tissue degrade resolution. To minimize optical crosstalk, we combined an optimized variant (eTsChR) of the most blue-shifted channelrhodopsin reported to-date with a nuclear-localized red-shifted Ca2+ indicator, H2B-jRGECO1a. To perform wide-area optically sectioned imaging in tissue, we designed a structured illumination technique that uses Hadamard matrices to encode spatial information. By combining these molecular and optical approaches we made wide-area functional maps in acute brain slices from mice of both sexes. The maps spanned cortex and striatum and probed the effects of antiepileptic drugs on neural excitability and the effects of AMPA and NMDA receptor blockers on functional connectivity. Together, these tools provide a powerful capability for wide-area mapping of neuronal excitability and functional connectivity in acute brain slices.SIGNIFICANCE STATEMENT A new technique for simultaneous optogenetic stimulation and calcium imaging across wide areas of brain slice enables high-throughput mapping of neuronal excitability and synaptic transmission.