Vision, choice, action, and behavioral engagement arise from neuronal activity that may be distributed across brain regions. Here we delineate the spatial distribution of neurons underlying these processes. We used Neuropixels probes 1,2 to record from ~30,000 neurons in 42 brain regions of mice performing a visual discrimination task 3. Neurons in nearly all regions responded non-specifically when the mouse initiated an action. By contrast, neurons encoding visual stimuli and upcoming choices occupied restricted regions in neocortex, basal ganglia, and midbrain. Choice signals were rare and emerged with indistinguishable timing across regions. Midbrain neurons were activated before contralateral choices and suppressed before ipsilateral choices, whereas forebrain neurons could prefer either side. Brain-wide pre-stimulus activity predicted engagement in individual trials and in the overall task, with enhanced subcortical but suppressed neocortical activity during engagement. These results reveal organizing principles for the distribution of neurons encoding behaviorally relevant variables across the mouse brain. Performing a perceptual decision involves processing sensory information, selecting actions that may lead to reward, and executing these actions. It is unknown how the neurons mediating these processes are distributed across brain regions, and whether they rely on circuits that are shared or distinct. Most studies of action selection (here referred to simply as choice) have focused on individual regions such as frontal, parietal, and motor cortex, basal ganglia, thalamus, cerebellum, and superior colliculus 4-11. However, neural correlates of movements, rewards, and other task variables have been observed in multiple brain regions, including in areas previously identified as purely sensory 12-24. It is therefore Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

SummaryResearch in neuroscience increasingly relies on the mouse, a mammalian species that affords unparalleled genetic tractability and brain atlases. Here, we introduce high-yield methods for probing mouse visual decisions. Mice are head-fixed, facilitating repeatable visual stimulation, eye tracking, and brain access. They turn a steering wheel to make two alternative choices, forced or unforced. Learning is rapid thanks to intuitive coupling of stimuli to wheel position. The mouse decisions deliver high-quality psychometric curves for detection and discrimination and conform to the predictions of a simple probabilistic observer model. The task is readily paired with two-photon imaging of cortical activity. Optogenetic inactivation reveals that the task requires mice to use their visual cortex. Mice are motivated to perform the task by fluid reward or optogenetic stimulation of dopamine neurons. This stimulation elicits a larger number of trials and faster learning. These methods provide a platform to accurately probe mouse vision and its neural basis.

Research in neuroscience relies increasingly on the mouse, a mammalian species that affords unparalleled genetic tractability and brain atlases. Here we introduce high-yield methods for probing mouse visual decisions. Mice are head-fixed, which facilitates repeatable visual stimulation, eye tracking, and brain access. They turn a steering wheel to make two-alternative choices, forced or unforced. Learning is rapid thanks to intuitive coupling of stimuli to wheel position. The mouse decisions deliver high-quality psychometric curves for detection and discrimination, and conform to the predictions of a simple probabilistic observer model. The task is readily paired with two-photon imaging of cortical activity. Optogenetic inactivation reveals that the task requires the visual cortex. Mice are motivated to perform the task by fluid reward or optogenetic stimulation of dopaminergic neurons. This stimulation elicits larger number of trials and faster learning. These methods provide a platform to accurately probe mouse vision and its neural basis.

Correlates of sensory stimuli and motor actions are found in multiple cortical areas, but such correlates do not indicate whether these areas are causally relevant to task performance. We trained mice to discriminate visual contrast and report their decision by steering a wheel. Widefield calcium imaging and Neuropixels recordings in cortex revealed stimulus-related activity in visual (VIS) and frontal (MOs) areas, and widespread movement-related activity across the whole dorsal cortex. Optogenetic inactivation biased choices only when targeted at VIS and MOs,proportionally to each site's encoding of the visual stimulus, and at times corresponding to peak stimulus decoding. A neurometric model based on summing and subtracting activity in VIS and MOs successfully described behavioral performance and predicted the effect of optogenetic inactivation. Thus, sensory signals localized in visual and frontal cortex play a causal role in task performance, while widespread dorsal cortical signals correlating with movement reflect processes that do not play a causal role.