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Two-photon (2-P) all-optical approaches combine 2-P calcium imaging and 2-P optogenetic modulations. Here, firstly, we combined juxtacellular recordings and GCaMP6f-based 2-P calcium imaging in mouse visual cortex to tune our detection algorithm towards a 100% specific identification of action potential-related calcium transients. Secondly, we minimized photostimulation artifacts by using extended-wavelength-spectrum laser sources for optogenetic stimulation. We achieved artifact-free all-optical experiments performing optogenetic stimulation from 1100 nm to 1300 nm. Thirdly, we determined the spectral range for maximizing efficacy until 1300 nm. The rate of evoked transients in GCaMP6f/C1V1-co-expressing cortical neurons peaked already at 1100 nm. By refining spike detection and defining 1100 nm as the optimal wavelength for artifact-free and effective GCaMP6f/C1V1-based all-optical physiology, we increased the translational value of these approaches, e.g., for the development of network-based therapies.
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http://dx.doi.org/10.1016/j.isci.2021.102184 | DOI Listing |
High-throughput profiling of neuronal activity at single-cell resolution is essential for advancing our understanding of brain function, enabling large-scale functional screens, and modeling neurological disorders. However, existing approaches are limited by scalability, manual data processing, and variability, thus restricting their ability to detect disease-associated phenotypes. Here, we present a scalable, open-source platform that integrates optogenetic stimulation, calcium imaging, automated data acquisition, and a fully integrated analysis pipeline.
View Article and Find Full Text PDFbioRxiv
August 2025
Department of Neuroscience, University of California, Berkeley.
To interpret complex sensory scenes, animals exploit statistical regularities to infer missing features and suppress redundant or ambiguous information. Cortical microcircuits might contribute to this cognitive goal by either completing or cancelling predictable activity, but it remains unknown whether, and how, a single circuit can implement these antagonistic computations. To address this central question, we used all-optical physiology to simulate sensory-evoked activity patterns in pyramidal cells (PCs) and somatostatin interneurons (SSTs) in the mouse's primary visual cortex (V1).
View Article and Find Full Text PDFNat Commun
July 2025
Institute of Basic Medical Sciences, Section of Physiology, University of Oslo, Oslo, Norway.
Gain modulation allows neurons to dynamically adjust their responsiveness to inputs without changing selectivity. While well-characterized in sensory areas, its role in higher-order brain regions governing spatial navigation and memory is unclear. Here, we used all-optical methods in mice performing a spatial task to demonstrate that vasoactive-intestinal peptide (VIP)-expressing neurons selectively control the gain of place cells and other cell types in the retrosplenial cortex (RSC) through disinhibition.
View Article and Find Full Text PDFJ Neural Eng
May 2025
Department of Electrical and Computer Engineering, University of Florida, Gainesville, FL, United States of America.
Brain computer interfaces (BCIs) require substantial cognitive flexibility to optimize control performance. Remarkably, learning this control is rapid, suggesting it might be mediated by neuroplasticity mechanisms operating on very short time scales. Here, we propose a meta plasticity model of BCI learning and skill consolidation at the single cell and population levels comprised of three elements: (a) behavioral time scale synaptic plasticity (BTSP), (b) intrinsic plasticity (IP) and (c) synaptic scaling (SS) operating at time scales from seconds to minutes to hours and days.
View Article and Find Full Text PDFACS Chem Neurosci
May 2025
Department of Neurosurgery, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, United States.
Simultaneous fiber photometry and optogenetics is a powerful emerging technique for precisely studying the interactions of neuronal brain networks. However, spectral overlap between photometry and optogenetic components has severely limited the application of an all-optical approach. Due to spectral overlap, light from optogenetic stimulation saturates the photosensor and occludes photometry fluorescence, which is especially problematic in physically smaller model organism brains like mice.
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