Friday, December 18, 2015

Be careful of simplistic interpretations in neuroscience

Fig from Südhof 2015.
A fascinating paper in Nature by Otchy et al called "Acute off-target effects of neural circuit manipulations"questions some of the simplistic assumptions behind many of the recent experiments in neuroscience.  As the authors summarise it: "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."

Fig 3f from Otchy et al showing how the song-
related dynamics of an example bird recover.
Basically they show that whereas transient lesions in critical areas can mess up complex behaviour, if the lesion is permanent then after a few days the behaviour recovers in the cases studied after a few days.

As they rightly say "Although efforts to understand the brain must necessarily rely on reductionist approaches, the simplifications and assumptions made in this pursuit must be scrutinized to prevent misleading conclusions... That the function of a circuit can be sensitive to sudden perturbations in chronically non-essential inputs is not surprising. The brain—a finely tuned, complex, and heavily interconnected dynamical system—operates in a fairly limited dynamic regime, making it plausible that local circuit perturbations could interfere with the dynamics and independent functions of remote circuits... The intricacies of dissecting interconnected biological networks and assigning functions to discrete nodes in those networks have been recognized in other contexts, including genetic and molecular networks. In such studies, the distinction between permissive and instructive functions is routinely made. Our results suggest that a similar distinction should be considered when interrogating the role of neural circuits in behaviour."

Otchy is a philosopher and coder turned neuroscientist and a PhD student of Bence Ölveczky at Harvard. Very interesting.

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