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Over the past few years, the various areas that surround the primary visual cortex (V1) in the mouse have been associated with many functions, ranging from higher order visual processing to decision-making. Recently, some studies have shown that higher order visual areas influence the activity of the primary visual cortex, refining its processing capabilities. Here, we studied how in vivo optogenetic inactivation of two higher order visual areas with different functional properties affects responses evoked by moving bars in the primary visual cortex. In contrast with the prevailing view, our results demonstrate that distinct higher order visual areas similarly modulate early visual processing. In particular, these areas enhance stimulus responsiveness in the primary visual cortex, by more strongly amplifying weaker compared with stronger sensory-evoked responses (for instance specifically amplifying responses to stimuli not moving along the direction preferred by individual neurons) and by facilitating responses to stimuli entering the receptive field of single neurons. Such enhancement, however, comes at the expense of orientation and direction selectivity, which increased when the selected higher order visual areas were inactivated. Thus, feedback from higher order visual areas selectively amplifies weak sensory-evoked V1 responses, which may enable more robust processing of visual stimuli.

Primary sensory cortices respond to crossmodal stimuli, for example auditory responses are found in primary visual cortex (V1). However, it remains unclear whether these responses reflect sensory inputs or behavioural modulation through sound-evoked body movement. We address this controversy by showing that sound-evoked activity in V1 of awake mice can be dissociated into auditory and behavioural components with distinct spatiotemporal profiles. The auditory component began at ∼27 ms, was found in superficial and deep layers and originated from auditory cortex, as shown by inactivation by muscimol. Sound-evoked orofacial movements correlated with V1 neural activity starting at ∼80-100 ms and explained auditory frequency-tuning. Visual, auditory and motor activity were expressed by segregated neuronal populations and during simultaneous audiovisual stimulation, visual representations remained dissociable from auditory and motor-related activity. This threefold dissociability of auditory, motor and visual processing is central to understanding how distinct inputs to visual cortex interact to support vision.

Primary sensory areas constitute crucial nodes during perceptual decision making. However, it remains unclear to what extent they mainly constitute a feedforward processing step, or rather are continuously involved in a recurrent network together with higher-order areas. We found that the temporal window in which primary visual cortex is required for the detection of identical visual stimuli was extended when task demands were increased via an additional sensory modality that had to be monitored. Late-onset optogenetic inactivation preserved bottom-up, early-onset responses which faithfully encoded stimulus features, and was effective in impairing detection only if it preceded a late, report-related phase of the cortical response. Increasing task demands were marked by longer reaction times and the effect of late optogenetic inactivation scaled with reaction time. Thus, independently of visual stimulus complexity, multisensory task demands determine the temporal requirement for ongoing sensory-related activity in V1, which overlaps with report-related activity.

Neurons in primary visual cortex (V1) may not only signal current visual input but also relevant contextual information such as reward expectancy and the subject’s spatial position. Such location-specific representations need not be restricted to V1 but could participate in a coherent mapping throughout sensory cortices. Here we show that spiking activity in primary auditory cortex (A1) and lateral, secondary visual cortex (V2L) of freely moving rats coherently represents a location-specific mapping in a sensory detection task performed on a figure-8 maze. Single-unit activity of both areas showed extensive similarities in terms of spatial distribution, reliability and position coding. Importantly, reconstructions of subject position on the basis of spiking activity displayed decoding errors that were correlated between areas in magnitude and direction. In addition to position, we found that head direction, but not locomotor speed or head angular velocity, was an important determinant of activity in A1 and V2L. Finally, pairs of units within and across areas showed significant correlations in instantaneous variability of firing rates (noise correlations). These were dependent on the spatial tuning of cells as well as the spatial position of the animal. We conclude that sensory cortices participate in coherent, multimodal representations of the subject’s sensory-specific location. These may provide a common reference frame for distributed cortical sensory and motor processes and may support crossmodal predictive processing.

SummaryOver the past few years, the various areas that surround the primary visual cortex in the mouse have been associated with many functions, ranging from higher-order visual processing to decision making. Recently, some studies have shown that higher-order visual areas influence the activity of the primary visual cortex, refining its processing capabilities. Here we studied how in vivo optogenetic inactivation of two higher-order visual areas with different functional properties affects responses evoked by moving bars in the primary visual cortex. In contrast with the prevailing view, our results demonstrate that distinct higher-order visual areas similarly modulate early visual processing. In particular, these areas broaden stimulus responsiveness in the primary visual cortex, by amplifying sensory-evoked responses for stimuli not moving along the orientation preferred by individual neurons. Thus, feedback from higher-order visual areas amplifies V1 responses to non-preferred stimuli, which may aid their detection.

Essential features of the world are often hidden and must be inferred by constructing internal models based on indirect evidence. Here, to study the mechanisms of inference we established a foraging task that is naturalistic and easily learned, yet can distinguish inference from simpler strategies such as the direct integration of sensory data. We show that both mice and humans learn a strategy consistent with optimal inference of a hidden state. However, humans acquire this strategy more than an order of magnitude faster than mice. Using optogenetics in mice we show that orbitofrontal and anterior cingulate cortex inactivation impact task performance, but only orbitofrontal inactivation reverts mice from an inference-based to a stimulus-bound decision strategy. These results establish a cross-species paradigm for studying the problem of inference-based decision-making and begin to dissect the network of brain regions crucial for its performance.

Summary Essential features of the world are often hidden and must be inferred by constructing internal models based on indirect evidence. Here, to study the mechanisms of inference, we establish a foraging task that is naturalistic and easily learned yet can distinguish inference from simpler strategies such as the direct integration of sensory data. We show that both mice and humans learn a strategy consistent with optimal inference of a hidden state. However, humans acquire this strategy more than an order of magnitude faster than mice. Using optogenetics in mice, we show that orbitofrontal and anterior cingulate cortex inactivation impacts task performance, but only orbitofrontal inactivation reverts mice from an inference-based to a stimulus-bound decision strategy. These results establish a cross-species paradigm for studying the problem of inference-based decision making and begins to dissect the network of brain regions crucial for its performance., Highlights • Naturalistic hidden-state foraging task • Disambiguation between stimulus-bound and inference-based foraging solutions • Both mice and humans can tune behavior to environment statistics • Differential role of orbito-frontal cortex and anterior cingulate cortex in inference, Vertechi et al. design a behavioral task to probe inference in mice and humans. They demonstrate that mice and humans adopt inference-based strategies, tuned to the environment statistics. Optogenetic inactivation reveals that the orbito-frontal cortex is necessary for this inference process.

The neuromodulator serotonin (5-HT) has been implicated in a variety of functions that involve patience or impulse control. Many of these effects are consistent with a long-standing theory that 5-HT promotes behavioral inhibition, a motivational bias favoring passive over active behaviors. To further test this idea, we studied the impact of 5-HT in a probabilistic foraging task, in which mice must learn the statistics of the environment and infer when to leave a depleted foraging site for the next. Critically, mice were required to actively nose-poke in order to exploit a given site. We show that optogenetic activation of 5-HT neurons in the dorsal raphe nucleus increases the willingness of mice to actively attempt to exploit a reward site before giving up. These results indicate that behavioral inhibition is not an adequate description of 5-HT function and suggest that a unified account must be based on a higher-order function., Serotonin (5-HT) has been suggested to promote waiting through behavioral inhibition. Here, the authors use an active foraging task and optogenetic activation of 5-HT neurons to show that rather than passivity, these neurons enhance persistence in the face of delay.

The neuromodulator serotonin (5-HT) has been implicated in a variety of functions that involve patience or impulse control. For example, activation of 5-HT neurons promotes waiting for delayed rewards. Many of these effects are consistent with a long-standing theory that 5-HT promotes behavioral inhibition, a motivational bias favoring passive over active behaviors. To further test this idea, we studied the impact of 5-HT in a probabilistic foraging task, in which mice must learn the statistics of the environment and infer when to leave a depleted foraging site for the next. Critically, mice were required to actively nose poke in order to exploit a given site. We found that optogenetic activation of 5-HT neurons in the dorsal raphe nucleus increased the willingness of mice to actively attempt to exploit a reward site before giving up. These results indicate that behavioral inhibition is not an adequate description of 5-HT function and suggest that a unified account must be based on a higher-order function.

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