An integrated microfluidic and fluorescence platform for probing in vivo neuropharmacology.

Journal: Neuron
Published Date:

Abstract

Neurotechnologies and genetic tools for dissecting neural circuit functions have advanced rapidly over the past decade although the development of complementary pharmacological methodologies has comparatively lagged. Understanding the precise pharmacological mechanisms of neuroactive compounds is critical for advancing basic neurobiology and neuropharmacology, as well as for developing more effective treatments for neurological and neuropsychiatric disorders. However, integrating modern tools for assessing neural activity in large-scale neural networks with spatially localized drug delivery remains a major challenge. Here, we present a dual microfluidic-photometry platform that enables simultaneous intracranial drug delivery with neural dynamics recording in the rodent brain. The integrated platform combines a wireless, battery-free, miniaturized fluidic microsystem with optical probes, allowing for spatially and temporally restricted drug delivery while sensing activity-dependent fluorescence using genetically encoded calcium indicators (GECIs), neurotransmitter sensors, and neuropeptide sensors. We demonstrate the performance of this platform for investigating neuropharmacological mechanisms in vivo in behaving mice.

Authors

  • Sean C Piantadosi
    Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA; Center of Excellence in Neurobiology of Addiction, Pain, and Emotion (NAPE), University of Washington, Seattle, WA, USA.
  • Min-Kyu Lee
    Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA; Neurolux Inc., Northfield, IL 60093, USA; Shirley Ryan AbilityLab, Chicago, IL 60611, USA; Department of Physical Medicine and Rehabilitation, Northwestern University, Chicago, IL 60611, USA.
  • Mingzheng Wu
    Emergency Center, Hubei Clinical Research Center for Emergency and Resuscitaion, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
  • Huong Huynh
    Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA; Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA.
  • Raudel Avila
    Department of Mechanical Engineering, Rice University, Houston, TX, USA; Department of Mechanical Engineering, Northwestern University, Evanston, IL 60208, USA.
  • Catalina A Zamorano
    Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA; Center of Excellence in Neurobiology of Addiction, Pain, and Emotion (NAPE), University of Washington, Seattle, WA, USA; Department of Pharmacology, University of Washington, Seattle, WA, USA.
  • Carina Pizzano
    Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA; Center of Excellence in Neurobiology of Addiction, Pain, and Emotion (NAPE), University of Washington, Seattle, WA, USA.
  • Yixin Wu
    Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA; Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA.
  • Rachael Xavier
    Neurolux Inc., Northfield, IL 60093, USA.
  • Maria Stanslaski
    Neurolux Inc., Northfield, IL 60093, USA.
  • Jiheon Kang
    Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA.
  • Sarah Thai
    Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA; Center of Excellence in Neurobiology of Addiction, Pain, and Emotion (NAPE), University of Washington, Seattle, WA, USA.
  • Youngdo Kim
    Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang, Republic of Korea.
  • Jinglan Zhang
    School of Microelectronics and Communication Engineering, Chongqing Key Laboratory of Bio-perception & Intelligent Information Processing, Chongqing University, Chongqing 400044 , P.R. China.
  • Yonggang Huang
    Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA.
  • Yevgenia Kozorovitskiy
    Department of Neurobiology, Northwestern University, Evanston, IL, USA; Chemistry of Life Processes Institutes, Northwestern University, Evanston, IL, USA.
  • Cameron H Good
    Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA; Neurolux Inc., Northfield, IL 60093, USA.
  • Anthony R Banks
    Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA; Neurolux Inc., Northfield, IL 60093, USA.
  • John A Rogers
    7Center for Bio-Integrated Electronics, Departments of Materials Science and Engineering, Biomedical Engineering, Chemistry, Mechanical Engineering, Electrical Engineering and Computer Science, Neurological Surgery, Simpson Querrey Institute for Nano/Biotechnology, McCormick School of Engineering, Feinberg School of Medicine, Northwestern University, Evanston, IL 60208 USA.
  • Michael R Bruchas
    Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA; Center of Excellence in Neurobiology of Addiction, Pain, and Emotion (NAPE), University of Washington, Seattle, WA, USA; Department of Pharmacology, University of Washington, Seattle, WA, USA; Department of Bioengineering, University of Washington, Seattle, WA, USA. Electronic address: mbruchas@uw.edu.