Acute off-target effects of neural circuit manipulations

Timothy M. Otchy, Steffen B. E. Wolff, Juliana Y. Rhee, Cengiz Pehlevan, Risa Kawai, Alexandre Kempf, Sharon M. H. Gobes and Bence P. Ölveczky ()
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Timothy M. Otchy: Center for Brain Science, Harvard University
Steffen B. E. Wolff: Center for Brain Science, Harvard University
Juliana Y. Rhee: Center for Brain Science, Harvard University
Cengiz Pehlevan: Center for Computational Biology, Simons Foundation
Risa Kawai: Center for Brain Science, Harvard University
Alexandre Kempf: Center for Brain Science, Harvard University
Sharon M. H. Gobes: Center for Brain Science, Harvard University
Bence P. Ölveczky: Center for Brain Science, Harvard University

Nature, 2015, vol. 528, issue 7582, 358-363

Abstract: Abstract Rapid and reversible manipulations of neural activity in behaving animals are transforming our understanding of brain function. An important assumption underlying much of this work is that evoked behavioural changes reflect the function of the manipulated circuits. We show that this assumption is problematic because it disregards indirect effects on the independent functions of downstream circuits. Transient inactivations of motor cortex in rats and nucleus interface (Nif) in songbirds severely degraded task-specific movement patterns and courtship songs, respectively, which are learned skills that recover spontaneously after permanent lesions of the same areas. We resolve this discrepancy in songbirds, showing that Nif silencing acutely affects the function of HVC, a downstream song control nucleus. Paralleling song recovery, the off-target effects resolved within days of Nif lesions, a recovery consistent with homeostatic regulation of neural activity in HVC. These results have implications for interpreting transient circuit manipulations and for understanding recovery after brain lesions.

Date: 2015
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DOI: 10.1038/nature16442

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