@article {69774, title = {Neuropixels Opto: Combining high-resolution electrophysiology and optogenetics}, journal = {bioRxiv}, year = {2025}, month = {2025 Feb 06}, abstract = {

High-resolution extracellular electrophysiology is the gold standard for recording spikes from distributed neural populations, and is especially powerful when combined with optogenetics for manipulation of specific cell types with high temporal resolution. We integrated these approaches into prototype Neuropixels Opto probes, which combine electronic and photonic circuits. These devices pack 960 electrical recording sites and two sets of 14 light emitters onto a 1 cm shank, allowing spatially addressable optogenetic stimulation with blue and red light. In mouse cortex, Neuropixels Opto probes delivered high-quality recordings together with spatially addressable optogenetics, differentially activating or silencing neurons at distinct cortical depths. In mouse striatum and other deep structures, Neuropixels Opto probes delivered efficient optotagging, facilitating the identification of two cell types in parallel. Neuropixels Opto probes represent an unprecedented tool for recording, identifying, and manipulating neuronal populations.

}, doi = {10.1101/2025.02.04.636286}, url = {https://www.biorxiv.org/content/early/2025/02/06/2025.02.04.636286}, author = {Lakunina, Anna and Socha, Karolina Z and Ladd, Alexander and Bowen, Anna J and Chen, Susu and Colonell, Jennifer and Doshi, Anjal and Karsh, Bill and Krumin, Michael and Kulik, Pavel and Li, Anna and Neutens, Pieter and O{\textquoteright}Callaghan, John and Olsen, Meghan and Putzeys, Jan and Tilmans, Harrie AC and Ye, Zhiwen and Welkenhuysen, Marleen and H{\"a}usser, Michael and Koch, Christof and Ting, Jonathan T. and Neuropixels Opto Consortium and Dutta, Barun and Harris, Timothy D and Steinmetz, Nicholas A and Svoboda, Karel and Siegle, Joshua H and Carandini, Matteo} } @article {70133, title = {Ultra-high-density Neuropixels probes improve detection and identification in neuronal recordings.}, journal = {Neuron}, year = {2025}, month = {2025 Sep 30}, abstract = {

To understand the neural basis of behavior, it is essential to sensitively and accurately measure neural activity at single-neuron and single-spike resolution. Extracellular electrophysiology delivers this, but it has biases in the neurons it detects and it imperfectly resolves their action potentials. To minimize these limitations, we developed a silicon probe with much smaller and denser recording sites than previous designs, called Neuropixels Ultra (NP Ultra). Using NP Ultra, neuronal yield in mouse visual cortex recordings increased by more than 2-fold. With ultra-high spatial resolution, we discovered that a feature of extracellular waveforms, the spatial extent or "footprint," distinguished axonal from somatic recordings. In addition, three genetically identified cortical cell types could be discriminated from one another with \~{}80\% accuracy and from other neurons with \~{}85\% accuracy. NP Ultra improves yield, detection of subcellular compartments, and cell type identification to enable a more powerful dissection of neural circuit activity during behavior.

bioRxiv preprint: doi.org/10.1101/2023.08.23.554527

}, issn = {1097-4199}, doi = {10.1016/j.neuron.2025.08.030}, url = {https://doi.org/10.1016/j.neuron.2025.08.030}, author = {Ye, Zhiwen and Shelton, Andrew M and Shaker, Jordan R and Boussard, Julien and Colonell, Jennifer and Birman, Daniel and Manavi, Sahar and Chen, Susu and Windolf, Charlie and Hurwitz, Cole and Yu, Han and Namima, Tomoyuki and Pedraja, Federico and Weiss, Shahaf and Raducanu, Bogdan C and Ness, Torbj{\o}rn V and Jia, Xiaoxuan and Mastroberardino, Giulia and Rossi, L Federico and Carandini, Matteo and H{\"a}usser, Michael and Einevoll, Gaute T and Laurent, Gilles and Sawtell, Nathaniel B and Bair, Wyeth and Pasupathy, Anitha and Mora Lopez, Carolina and Dutta, Barundeb and Paninski, Liam and Siegle, Joshua H and Koch, Christof and Olsen, Shawn R and Harris, Timothy D and Steinmetz, Nicholas A} } @article {68968, title = {Ultra-high density electrodes improve detection, yield, and cell type specificity of brain recordings.}, journal = {bioRxiv}, year = {2023}, month = {2023 Aug 25}, abstract = {

To study the neural basis of behavior, we require methods to sensitively and accurately measure neural activity at single neuron and single spike resolution. Extracellular electrophysiology is a principal method for achieving this, but it has biases in the neurons it detects and it imperfectly resolves their action potentials. To overcome these limitations, we developed a silicon probe with significantly smaller and denser recording sites than previous designs, called Neuropixels Ultra (NP Ultra). This device measures neuronal activity at ultra-high densities (\>1300 sites per mm, 10 times higher than previous probes), with 6 {\textmu}m center-to-center spacing and low noise. This device effectively comprises an implantable voltage-sensing camera that captures a planar image of a neuron{\textquoteright}s electrical field. We introduce a new spike sorting algorithm optimized for these probes and use it to find that the yield of visually-responsive neurons in recordings from mouse visual cortex improves \~{}3-fold. Recordings across multiple brain regions and four species revealed a subset of unexpectedly small extracellular action potentials not previously reported. Further experiments determined that, in visual cortex, these do not correspond to major subclasses of interneurons and instead likely reflect recordings from axons. Finally, using ground-truth identification of cortical inhibitory cell types with optotagging, we found that cell type was discriminable with approximately 75\% success among three types, a significant improvement over lower-resolution recordings. NP Ultra improves spike sorting performance, sampling bias, and cell type classification.

}, doi = {10.1101/2023.08.23.554527}, author = {Ye, Zhiwen and Shelton, Andrew M and Shaker, Jordan R and Boussard, Julien and Colonell, Jennifer and Manavi, Sahar and Chen, Susu and Windolf, Charlie and Hurwitz, Cole and Namima, Tomoyuki and Pedraja, Federico and Weiss, Shahaf and Raducanu, Bogdan and Ness, Torbj{\o}rn V and Einevoll, Gaute T and Laurent, Gilles and Sawtell, Nathaniel B and Bair, Wyeth and Pasupathy, Anitha and Mora Lopez, Carolina and Dutta, Barun and Paninski, Liam and Siegle, Joshua H and Koch, Christof and Olsen, Shawn R and Harris, Timothy D and Steinmetz, Nicholas A} } @article {67232, title = {Neuropixels 2.0: A miniaturized high-density probe for stable, long-term brain recordings.}, journal = {Science}, volume = {372}, year = {2021}, month = {2021 Apr 16}, abstract = {

Measuring the dynamics of neural processing across time scales requires following the spiking of thousands of individual neurons over milliseconds and months. To address this need, we introduce the Neuropixels 2.0 probe together with newly designed analysis algorithms. The probe has more than 5000 sites and is miniaturized to facilitate chronic implants in small mammals and recording during unrestrained behavior. High-quality recordings over long time scales were reliably obtained in mice and rats in six laboratories. Improved site density and arrangement combined with newly created data processing methods enable automatic post hoc correction for brain movements, allowing recording from the same neurons for more than 2 months. These probes and algorithms enable stable recordings from thousands of sites during free behavior, even in small animals such as mice.

}, issn = {1095-9203}, doi = {10.1126/science.abf4588}, author = {Steinmetz, Nicholas A and Ayd{\i}n, {\c C}a{\u g}atay and Lebedeva, Anna and Okun, Michael and Pachitariu, Marius and Bauza, Marius and Beau, Maxime and Bhagat, Jai and B{\"o}hm, Claudia and Broux, Martijn and Chen, Susu and Colonell, Jennifer and Gardner, Richard J and Karsh, Bill and Kloosterman, Fabian and Kostadinov, Dimitar and Mora-Lopez, Carolina and O{\textquoteright}Callaghan, John and Park, Junchol and Putzeys, Jan and Sauerbrei, Britton and van Daal, Rik J J and Vollan, Abraham Z and Wang, Shiwei and Welkenhuysen, Marleen and Ye, Zhiwen and Dudman, Joshua T and Dutta, Barundeb and Hantman, Adam W and Harris, Kenneth D and Lee, Albert K and Moser, Edvard I and O{\textquoteright}Keefe, John and Renart, Alfonso and Svoboda, Karel and H{\"a}usser, Michael and Haesler, Sebastian and Carandini, Matteo and Harris, Timothy D} }