Multimodal in vivo brain electrophysiology with integrated glass microelectrodes

ABSTRACT Electrophysiology is the most used approach for the collection of functional data in basic and translational neuroscience, but it is typically limited to either intracellular or

extracellular recordings. The integration of multiple physiological modalities for the routine acquisition of multimodal data with microelectrodes could be useful for biomedical

applications, yet this has been challenging owing to incompatibilities of fabrication methods. Here, we present a suite of glass pipettes with integrated microelectrodes for the simultaneous

acquisition of multimodal intracellular and extracellular information in vivo, electrochemistry assessments, and optogenetic perturbations of neural activity. We used the integrated devices

to acquire multimodal signals from the CA1 region of the hippocampus in mice and rats, and show that these data can serve as ground-truth validation for the performance of spike-sorting

algorithms. The microdevices are applicable for basic and translational neurobiology, and for the development of next-generation brain–machine interfaces. Access through your institution Buy

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MICROELECTRODE ARRAYS FOR NEUROSCIENCE Article 08 May 2025 A SOFT, HIGH-DENSITY NEUROELECTRONIC ARRAY Article Open access 22 August 2023 IMPLANTABLE INTRACORTICAL MICROELECTRODES: REVIEWING

THE PRESENT WITH A FOCUS ON THE FUTURE Article Open access 05 January 2023 DATA AVAILABILITY The authors declare that all data supporting the findings of this study are available within the

paper and its Supplementary information. The raw data acquired in this study are available from the corresponding author on reasonable request. CODE AVAILABILITY The custom routines for

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thank A. Pais, D. Lee, V. Reddy, H. Esmailbeigi, B. Bowers, B. Biddle, J. Macklin, R. Patel, W. Sun, B. Barbarits, J. Venton, E. Privman, P. Ahamad and L. Coddington for their valuable

contributions to this study. We would also like to thank J. Markara and B. Andrasfalvy for helpful discussions. This work was supported by the Howard Hughes Medical Institute. AUTHOR

INFORMATION AUTHORS AND AFFILIATIONS * Howard Hughes Medical Institute, Janelia Research Campus, Ashburn, VA, USA David L. Hunt, Chongxi Lai, Richard D. Smith, Albert K. Lee, Timothy D.

Harris & Mladen Barbic Authors * David L. Hunt View author publications You can also search for this author inPubMed Google Scholar * Chongxi Lai View author publications You can also

search for this author inPubMed Google Scholar * Richard D. Smith View author publications You can also search for this author inPubMed Google Scholar * Albert K. Lee View author

publications You can also search for this author inPubMed Google Scholar * Timothy D. Harris View author publications You can also search for this author inPubMed Google Scholar * Mladen

Barbic View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS D.L.H., A.K.L., T.D.H. and M.B. conceived the project. T.D.H. supervised the

project. M.B. developed and fabricated all multimodal devices. A.K.L. and M.B. aquired data with the Patch-Tritrode. D.L.H. and C.L. analysed the Patch-Tritrode data. D.L.H. and M.B. aquired

data with the Patch-Silvertrode. D.L.H. analysed the Patch-Silvertrode data. R.D.S. and M.B. aquired Patch-Carbontrode data. D.L.H. and R.D.S. analysed the Patch-Carbontrode data. D.L.H.

and M.B. wrote the manuscript with input from all authors. CORRESPONDING AUTHORS Correspondence to David L. Hunt or Mladen Barbic. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare

no competing interests. ADDITIONAL INFORMATION PUBLISHER’S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION Supplementary figures. REPORTING SUMMARY RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Hunt, D.L.,

Lai, C., Smith, R.D. _et al._ Multimodal in vivo brain electrophysiology with integrated glass microelectrodes. _Nat Biomed Eng_ 3, 741–753 (2019). https://doi.org/10.1038/s41551-019-0373-8

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