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

Peter M. Eimon (), Mostafa Ghannad-Rezaie, Gianluca De Rienzo, Amin Allalou, Yuelong Wu, Mu Gao, Ambrish Roy, Jeffrey Skolnick and Mehmet Fatih Yanik ()
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Peter M. Eimon: Massachusetts Institute of Technology
Mostafa Ghannad-Rezaie: Massachusetts Institute of Technology
Gianluca De Rienzo: Massachusetts Institute of Technology
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

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-017-02404-4

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