Uncertain then, irrelevant now

Abstract

understood — in fact, only exists — at the pop-ulation level. And because the neural trajecto-ries in the model closely resembled the neural trajectories in the data, Mante et al. propose this principle as the neural basis of flexible, context-dependent processing. This fascinating study raises some intrigu-ing questions. First, how do we go beyond correlations and causally test the authors' pro-posed principle? With existing perturbation methods, we cannot align manipulations with the critical axes that define the population's dynamical behaviour. Second, is the region of PFC that the authors recorded from even nec-essary for the context-dependent behaviour investigated here? The behavioural task used is new, so this question has never been addressed. Third, the conclusions on the behaviour of neural populations are based on data from many separate single-neuron recordings. Will the same principles hold when multi-neuron recordings are used to directly see the popula-tion neural trajectories in single trials? Finally, what is the specific mechanism that the net-work uses to change its quenching directions? These questions aside, Mante et al. have led the field with novel and deep ideas that should drive much discussion and thinking. ■