Genetically encoded calcium indicators (GECIs) enable imaging of in vivo brain cell activity with high sensitivity and specificity. In contrast to viral infection or in utero electroporation, indicator expression in transgenic reporter lines is induced noninvasively, reliably, and homogenously. Recently, Cre/tTA-dependent reporter mice were introduced, which provide high-level expression of green fluorescent GECIs in a cell-type-specific and inducible manner when crossed with Cre and tTA driver mice. Here, we generated and characterized the first red-shifted GECI reporter line of this type using R-CaMP1.07, a red fluorescent indicator that is efficiently two-photon excited above 1000 nm. By crossing the new R-CaMP1.07 reporter line to Cre lines driving layer-specific expression in neocortex we demonstrate its high fidelity for reporting action potential firing in vivo, long-term stability over months, and versatile use for functional imaging of excitatory neurons across all cortical layers, especially in the previously difficult to access layers 4 and 6.

Soft, stretchable materials hold great promise for the fabrication of biomedical devices due to their capacity to integrate gracefully with and conform to biological tissues. Conformal devices are of particular interest in the development of brain interfaces where rigid structures can lead to tissue damage and loss of signal quality over the lifetime of the implant. Interfaces to study brain function and dysfunction increasingly require multimodal access in order to facilitate measurement of diverse physiological signals that span the disparate temporal and spatial scales of brain dynamics. Here the Opto‐e‐Dura, a soft, stretchable, 16‐channel electrocorticography array that is optically transparent is presented. Its compatibility with diverse optical and electrical readouts is demonstrated enabling multimodal studies that bridge spatial and temporal scales. The device is chronically stable for weeks, compatible with wide‐field and 2‐photon calcium imaging and permits the repeated insertion of penetrating multielectrode arrays. As the variety of sensors and effectors realizable on soft, stretchable substrates expands, similar devices that provide large‐scale, multimodal access to the brain will continue to improve fundamental understanding of brain function.

AbstractSoft, stretchable materials hold great promise for the fabrication of biomedical devices due to their capacity to integrate gracefully with and conform to biological tissues. Conformal devices are of particular interest in the development of brain interfaces where rigid structures can lead to tissue damage and loss of signal quality over the lifetime of the implant. Interfaces to study brain function and dysfunction increasingly require multimodal access in order to facilitate measurement of diverse physiological signals that span the disparate temporal and spatial scales of brain dynamics. Here we present the Opto-e-Dura, a soft, stretchable, 16-channel electrocorticography array that is optically transparent. We demonstrate its compatibility with diverse optical and electrical readouts enabling multimodal studies that bridge spatial and temporal scales. The device is chronically stable for weeks, compatible with wide-field and 2-photon calcium imaging and permits the repeated insertion of penetrating multi-electrode arrays. As the variety of sensors and effectors realizable on soft, stretchable substrates expands, similar devices that provide large-scale, multimodal access to the brain will continue to improve fundamental understanding of brain function.