A Confound for Function Localization: Acute Off-target Effects of Neural Circuit Manipulations


November 4, 2015 - 1:00pm
Northwest 243
About the Speaker
Tim Otchy (Ölveczky Lab)

Assigning function to brain areas is a principal aim of neuroscience that is often pursued by rapidly and reversibly manipulating neural activity in behaving animals. An important assumption underlying this experimental regime is that consequent behavioral changes reflect the function of the targeted circuits. I will present evidence demonstrating that this assumption is problematic in that it fails to account for indirect effects on the independent functions of circuits downstream of the targeted area.

Transient inactivation of sensorimotor area Nif in songbirds and motor cortex in rats severely disrupts courtship songs and task-specific movement patterns – learned skills that recover spontaneously after permanent lesions of the same areas. How can a brain area be both essential for behavior execution (as assayed by the now preferred method, transient perturbation) and not (as assayed by the traditional method, lesions)? I resolve this seeming paradox in songbirds, showing that sudden silencing of Nif disrupts song and neural dynamics within HVC, a downstream song control nucleus. In parallel with song recovery, the off-target effects resolved within days of lesion, a recovery consistent with homeostatic regulation of neural activity within HVC. These finding have broad implications for how neural circuit manipulations are interpreted and for understanding the mechanisms supporting functional recovery following brain injury.