title: Acute off-target effects of neural circuit manipulations.
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.
authors.affiliation: Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, USA.|Program in Neuroscience, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Otchy
authors.affiliation: Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Steffen B E
authors.initials: SB
authors.lastname: Wolff
authors.affiliation: Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Juliana Y
authors.initials: JY
authors.lastname: Rhee
authors.affiliation: Center for Computational Biology, Simons Foundation, New York, New York 10010, USA.
authors.forename: Cengiz
authors.initials: C
authors.lastname: Pehlevan
authors.affiliation: Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Risa
authors.initials: R
authors.lastname: Kawai
authors.affiliation: Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Kempf
authors.affiliation: Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Sharon M H
authors.initials: SM
authors.lastname: Gobes
authors.affiliation: Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, USA.|Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Bence P
authors.initials: BP
authors.lastname: Ölveczky
mesh_terms: D000818:Animals; D016477:Artifacts; D003380:Courtship; D005260:Female; D046369:Finches / Q000502:physiology; D006706:Homeostasis; D007858:Learning / Q000502:physiology; D008297:Male; D009044:Motor Cortex / Q000166:cytology / Q000293:injuries / Q000502:physiology; D009068:Movement / Q000502:physiology; D017072:Neostriatum / Q000166:cytology / Q000293:injuries / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology*; D062308:Optogenetics / Q000379:methods; D011597:Psychomotor Performance / Q000502:physiology; D020318:Rats, Long-Evans; D014828:Vocalization, Animal / Q000502:physiology