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Brain activity patterns in high-throughput electrophysiology screen predict both drug efficacies and side effects

Author

Listed:
  • Peter M. Eimon

    (Massachusetts Institute of Technology)

  • Mostafa Ghannad-Rezaie

    (Massachusetts Institute of Technology
    UZH/ETH Irchel Campus)

  • Gianluca De Rienzo

    (Massachusetts Institute of Technology
    Intellimedix
    Axcella Health)

  • Amin Allalou

    (Massachusetts Institute of Technology)

  • Yuelong Wu

    (Massachusetts Institute of Technology)

  • Mu Gao

    (Georgia Institute of Technology)

  • Ambrish Roy

    (Georgia Institute of Technology)

  • Jeffrey Skolnick

    (Georgia Institute of Technology)

  • Mehmet Fatih Yanik

    (Massachusetts Institute of Technology
    UZH/ETH Irchel Campus)

Abstract

Neurological drugs are often associated with serious side effects, yet drug screens typically focus only on efficacy. We demonstrate a novel paradigm utilizing high-throughput in vivo electrophysiology and brain activity patterns (BAPs). A platform with high sensitivity records local field potentials (LFPs) simultaneously from many zebrafish larvae over extended periods. We show that BAPs from larvae experiencing epileptic seizures or drug-induced side effects have substantially reduced complexity (entropy), similar to reduced LFP complexity observed in Parkinson’s disease. To determine whether drugs that enhance BAP complexity produces positive outcomes, we used light pulses to trigger seizures in a model of Dravet syndrome, an intractable genetic epilepsy. The highest-ranked compounds identified by BAP analysis exhibit far greater anti-seizure efficacy and fewer side effects during subsequent in-depth behavioral assessment. This high correlation with behavioral outcomes illustrates the power of brain activity pattern-based screens and identifies novel therapeutic candidates with minimal side effects.

Suggested Citation

  • Peter M. Eimon & Mostafa Ghannad-Rezaie & Gianluca De Rienzo & Amin Allalou & Yuelong Wu & Mu Gao & Ambrish Roy & Jeffrey Skolnick & Mehmet Fatih Yanik, 2018. "Brain activity patterns in high-throughput electrophysiology screen predict both drug efficacies and side effects," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02404-4
    DOI: 10.1038/s41467-017-02404-4
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    Cited by:

    1. Yousang Yoon & Hyogeun Shin & Donghak Byun & Jiwan Woo & Yakdol Cho & Nakwon Choi & Il-Joo Cho, 2022. "Neural probe system for behavioral neuropharmacology by bi-directional wireless drug delivery and electrophysiology in socially interacting mice," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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