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Opinion, Cognition and Behavior

Toward standardized guidelines for investigating neural circuit control of behavior in animal research

Alan S. Lewis, Erin S. Calipari and Cody A. Siciliano
eNeuro 29 March 2021, ENEURO.0498-20.2021; DOI: https://doi.org/10.1523/ENEURO.0498-20.2021
Alan S. Lewis
1Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, 37212, USA
2Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, 37232, USA
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Erin S. Calipari
2Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, 37232, USA
3Department of Pharmacology, Vanderbilt University, Nashville, TN, 37232, USA
4Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN, 37232, USA
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Cody A. Siciliano
2Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, 37232, USA
3Department of Pharmacology, Vanderbilt University, Nashville, TN, 37232, USA
4Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN, 37232, USA
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Abstract

With the advent of tools for recording and manipulating activity with high spatiotemporal resolution in defined neural circuits in behaving animals, behavioral neuroscience is now tasked with establishing field-wide standards for implementing and interpreting these powerful approaches. Theoretical frameworks for what constitute proof of fundamental neurobiological principles is an ongoing and frequently debated topic. On the other hand, standardizing interpretation of individual experimental findings to avoid spurious conclusions in practice has received less attention. Even within subfields, similar assays are often used to support widely disparate conclusions which in part has contributed to a slew of studies claiming highly specified functions for cell-types and circuits which are often in direct disagreement with one another. In this opinion piece, we discuss common pitfalls in design and interpretation of approaches for recording or manipulating neural activity in animal models of motivated behavior. We emphasize the importance of integrating findings across multiple behavioral assays concomitant with tempered inference regarding specialized neuronal functions as a standardized starting point for parsing circuit control of behavior. Our aim is to stimulate an open and accessible discourse in the literature to address issues of continuity across behavioral neurosciences.

SIGNIFICANCE STATEMENT

New technologies in neuroscience allow for increasingly precise recording and stimulation of neural circuits in animal research. The goal is to understand the function of the brain, as well as to develop new ways to treat brain diseases. Yet despite seemingly boundless technical potential, a key limitation for meaningful advances stems from spurious interpretation of experiments. Here we provide specific examples from our own studies and discuss why appropriate interpretation of results can be challenging. We emphasize that standardizing interpretation of behavioral assays, as well as transferring incentives for identifying “specific” circuits to more objectively understanding a circuit’s role across varied behavioral domains, will facilitate assimilation across literatures and ultimately move behavioral neuroscience closer to its goals.

  • Behavior
  • Behavioral Neuroscience
  • Chemogenetics
  • Circuits
  • In vivo imaging
  • Optogenetics

Footnotes

  • The authors report no conflict of interest.

  • This work was supported by National Institutes of Health grants MH116339 (A.S.L.), DA042111 and DA048931 (E.S.C.), DA045103 (C.A.S.), the Brain and Behavior Research Foundation (E.S.C, C.A.S.), the Brain Research Foundation (C.A.S.), Alkermes Pharmaceuticals (C.A.S.), the Whitehall Foundation (E.S.C.), and the Edward Mallinckrodt Jr. Foundation (E.S.C.)

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

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Toward standardized guidelines for investigating neural circuit control of behavior in animal research
Alan S. Lewis, Erin S. Calipari, Cody A. Siciliano
eNeuro 29 March 2021, ENEURO.0498-20.2021; DOI: 10.1523/ENEURO.0498-20.2021

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Toward standardized guidelines for investigating neural circuit control of behavior in animal research
Alan S. Lewis, Erin S. Calipari, Cody A. Siciliano
eNeuro 29 March 2021, ENEURO.0498-20.2021; DOI: 10.1523/ENEURO.0498-20.2021
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Keywords

  • Behavior
  • Behavioral Neuroscience
  • Chemogenetics
  • Circuits
  • In vivo imaging
  • Optogenetics

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