Dissociating instructive from permissive roles of brain circuits with reversible neural activity manipulations

Read the full article See related articles

Listed in

This article is not in any list yet, why not add it to one of your lists.
Log in to save this article


Neuroscientists rely on targeted perturbations and lesions to causally map functions in the brain 1 . Yet, since the brain is highly interconnected, manipulation of one area can impact behavior through indirect effects on many other brain regions, complicating the interpretation of such results 2,3 . On the other hand, the often-observed recovery of behavior performance after lesion can cast doubt on whether the lesioned area was ever directly involved 4,5 . Recent studies have highlighted how the results of acute and irreversible inactivation can directly conflict 4-6 , making it unclear whether a brain area is instructive or merely permissive in a specific brain function. To overcome this challenge, we developed a three-stage optogenetic approach which leverages the ability to precisely control the temporal period of regional inactivation with either brief or sustained illumination. Using a visual detection task, we found that acute optogenetic inactivation of the primary visual cortex (V1) suppressed task performance if cortical inactivation was intermittent across trials within each behavioral session. However, when we inactivated V1 for entire behavioral sessions, animals quickly recovered performance in just one to two days. Most importantly, after returning these recovered animals to intermittent cortical inactivation, they quickly reverted to failing on optogenetic inactivation trials. These data support a revised model where the cortex is the default circuit that instructs perceptual performance in basic sensory tasks. More generally, this novel, temporally controllable optogenetic perturbation paradigm can be broadly applied to brain circuits and specific cell types to assess whether they are instructive or merely permissive in a brain function or behavior.

Article activity feed