A brain-wide map of neural activity during complex behaviour.

A key challenge in neuroscience is understanding how neurons in hundreds of interconnected brain regions integrate sensory inputs with previous expectations to initiate movements and make decisions. It is difficult to meet this challenge if different laboratories apply different analyses to different recordings in different regions during different behaviours. Here we report a comprehensive set of recordings from 621,733 neurons recorded with 699 Neuropixels probes across 139 mice in 12 laboratories.

Brain-wide representations of prior information in mouse decision-making.

The neural representations of prior information about the state of the world are poorly understood. Here, to investigate them, we examined brain-wide Neuropixels recordings and widefield calcium imaging collected by the International Brain Laboratory. Mice were trained to indicate the location of a visual grating stimulus, which appeared on the left or right with a prior probability alternating between 0.

Brain-wide dynamics linking sensation to action during decision-making.

Perceptual decisions rely on learned associations between sensory evidence and appropriate actions, involving the filtering and integration of relevant inputs to prepare and execute timely responses. Despite the distributed nature of task-relevant representations, it remains unclear how transformations between sensory input, evidence integration, motor planning and execution are orchestrated across brain areas and dimensions of neural activity. Here we addressed this question by recording brain-wide neural activity in mice learning to report changes in ambiguous visual input.

Cooperative thalamocortical circuit mechanism for sensory prediction errors.

The brain functions as a prediction machine, utilizing an internal model of the world to anticipate sensations and the outcomes of our actions. Discrepancies between expected and actual events, referred to as prediction errors, are leveraged to update the internal model and guide our attention towards unexpected events. Despite the importance of prediction-error signals for various neural computations across the brain, surprisingly little is known about the neural circuit mechanisms responsible for their implementation.

Functional specificity of recurrent inhibition in visual cortex.

In the neocortex, neural activity is shaped by the interaction of excitatory and inhibitory neurons, defined by the organization of their synaptic connections. Although connections among excitatory pyramidal neurons are sparse and functionally tuned, inhibitory connectivity is thought to be dense and largely unstructured. By measuring in vivo visual responses and synaptic connectivity of parvalbumin-expressing (PV+) inhibitory cells in mouse primary visual cortex, we show that the synaptic weights of their connections to nearby pyramidal neurons are specifically tuned according to the similarity of the cells' responses.

Learning shapes cortical dynamics to enhance integration of relevant sensory input.

Adaptive sensory behavior is thought to depend on processing in recurrent cortical circuits, but how dynamics in these circuits shapes the integration and transmission of sensory information is not well understood. Here, we study neural coding in recurrently connected networks of neurons driven by sensory input. We show analytically how information available in the network output varies with the alignment between feedforward input and the integrating modes of the circuit dynamics.

Independent response modulation of visual cortical neurons by attentional and behavioral states.

Sensory processing is influenced by cognitive and behavioral states, but how these states interact to modulate responses of individual neurons is unknown. We trained mice in a visual discrimination task wherein they attended to different locations within a hemifield while running or sitting still, enabling us to examine how visual responses are modulated by spatial attention and running behavior. We found that spatial attention improved discrimination performance and strengthened visual responses of excitatory neurons in the primary visual cortex whose receptive fields overlapped with the attended location.

Antibody stabilization for thermally accelerated deep immunostaining.

Antibodies have diverse applications due to their high reaction specificities but are sensitive to denaturation when a higher working temperature is required. We have developed a simple, highly scalable and generalizable chemical approach for stabilizing off-the-shelf antibodies against thermal and chemical denaturation. We demonstrate that the stabilized antibodies (termed SPEARs) can withstand up to 4 weeks of continuous heating at 55 °C and harsh denaturants, and apply our method to 33 tested antibodies.

Cortical feedback loops bind distributed representations of working memory.

Working memory-the brain's ability to internalize information and use it flexibly to guide behaviour-is an essential component of cognition. Although activity related to working memory has been observed in several brain regions, how neural populations actually represent working memory and the mechanisms by which this activity is maintained remain unclear. Here we describe the neural implementation of visual working memory in mice alternating between a delayed non-match-to-sample task and a simple discrimination task that does not require working memory but has identical stimulus, movement and reward statistics.

Learning and attention increase visual response selectivity through distinct mechanisms.

Selectivity of cortical neurons for sensory stimuli can increase across days as animals learn their behavioral relevance and across seconds when animals switch attention. While both phenomena occur in the same circuit, it is unknown whether they rely on similar mechanisms. We imaged primary visual cortex as mice learned a visual discrimination task and subsequently performed an attention switching task.

Standardized and reproducible measurement of decision-making in mice.

Progress in science requires standardized assays whose results can be readily shared, compared, and reproduced across laboratories. Reproducibility, however, has been a concern in neuroscience, particularly for measurements of mouse behavior. Here, we show that a standardized task to probe decision-making in mice produces reproducible results across multiple laboratories.

Mesoscale cortical dynamics reflect the interaction of sensory evidence and temporal expectation during perceptual decision-making.

How sensory evidence is transformed across multiple brain regions to influence behavior remains poorly understood. We trained mice in a visual change detection task designed to separate the covert antecedents of choices from activity associated with their execution. Wide-field calcium imaging across the dorsal cortex revealed fundamentally different dynamics of activity underlying these processes.

The sensory representation of causally controlled objects.

Intentional control over external objects is informed by our sensory experience of them. To study how causal relationships are learned and effected, we devised a brain machine interface (BMI) task using wide-field calcium signals. Mice learned to entrain activity patterns in arbitrary pairs of cortical regions to guide a visual cursor to a target location for reward.

Cortico-cerebellar interactions during goal-directed behavior.

Preparatory activity is observed across multiple interconnected brain regions before goal-directed movement. Preparatory activity reflects discrete activity states representing specific future actions. It is unclear how this activity is mediated by multi-regional interactions.

Cerebellar Contribution to Preparatory Activity in Motor Neocortex.

In motor neocortex, preparatory activity predictive of specific movements is maintained by a positive feedback loop with the thalamus. Motor thalamus receives excitatory input from the cerebellum, which learns to generate predictive signals for motor control. The contribution of this pathway to neocortical preparatory signals remains poorly understood.

Locomotion-dependent remapping of distributed cortical networks.

The interactions between neocortical areas are fluid and state-dependent, but how individual neurons couple to cortex-wide network dynamics remains poorly understood. We correlated the spiking of neurons in primary visual (V1) and retrosplenial (RSP) cortex to activity across dorsal cortex, recorded simultaneously by widefield calcium imaging. Neurons were correlated with distinct and reproducible patterns of activity across the cortical surface; while some fired predominantly with their local area, others coupled to activity in distal areas.

Segregated Subnetworks of Intracortical Projection Neurons in Primary Visual Cortex.

The rules by which neurons in neocortex choose their synaptic partners are not fully understood. In sensory cortex, intermingled neurons encode different attributes of sensory inputs and relay them to different long-range targets. While neurons with similar responses to sensory stimuli make connections preferentially, the relationship between synaptic connectivity within an area and long-range projection target remains unclear.

Predictive Processing: A Canonical Cortical Computation.

This perspective describes predictive processing as a computational framework for understanding cortical function in the context of emerging evidence, with a focus on sensory processing. We discuss how the predictive processing framework may be implemented at the level of cortical circuits and how its implementation could be falsified experimentally. Lastly, we summarize the general implications of predictive processing on cortical function in healthy and diseased states.

Distinct learning-induced changes in stimulus selectivity and interactions of GABAergic interneuron classes in visual cortex.

How learning enhances neural representations for behaviorally relevant stimuli via activity changes of cortical cell types remains unclear. We simultaneously imaged responses of pyramidal cells (PYR) along with parvalbumin (PV), somatostatin (SOM), and vasoactive intestinal peptide (VIP) inhibitory interneurons in primary visual cortex while mice learned to discriminate visual patterns. Learning increased selectivity for task-relevant stimuli of PYR, PV and SOM subsets but not VIP cells.

The logic of single-cell projections from visual cortex.

Neocortical areas communicate through extensive axonal projections, but the logic of information transfer remains poorly understood, because the projections of individual neurons have not been systematically characterized. It is not known whether individual neurons send projections only to single cortical areas or distribute signals across multiple targets. Here we determine the projection patterns of 591 individual neurons in the mouse primary visual cortex using whole-brain fluorescence-based axonal tracing and high-throughput DNA sequencing of genetically barcoded neurons (MAPseq).

Assessing the Role of Inhibition in Stabilizing Neocortical Networks Requires Large-Scale Perturbation of the Inhibitory Population.

Neurons within cortical microcircuits are interconnected with recurrent excitatory synaptic connections that are thought to amplify signals (Douglas and Martin, 2007), form selective subnetworks (Ko et al., 2011), and aid feature discrimination. Strong inhibition (Haider et al.

Stimulus relevance modulates contrast adaptation in visual cortex.

A general principle of sensory processing is that neurons adapt to sustained stimuli by reducing their response over time. Most of our knowledge on adaptation in single cells is based on experiments in anesthetized animals. How responses adapt in awake animals, when stimuli may be behaviorally relevant or not, remains unclear.

Model Constrained by Visual Hierarchy Improves Prediction of Neural Responses to Natural Scenes.

Accurate estimation of neuronal receptive fields is essential for understanding sensory processing in the early visual system. Yet a full characterization of receptive fields is still incomplete, especially with regard to natural visual stimuli and in complete populations of cortical neurons. While previous work has incorporated known structural properties of the early visual system, such as lateral connectivity, or imposing simple-cell-like receptive field structure, no study has exploited the fact that nearby V1 neurons share common feed-forward input from thalamus and other upstream cortical neurons.

Learning Enhances Sensory and Multiple Non-sensory Representations in Primary Visual Cortex.

We determined how learning modifies neural representations in primary visual cortex (V1) during acquisition of a visually guided behavioral task. We imaged the activity of the same layer 2/3 neuronal populations as mice learned to discriminate two visual patterns while running through a virtual corridor, where one pattern was rewarded. Improvements in behavioral performance were closely associated with increasingly distinguishable population-level representations of task-relevant stimuli, as a result of stabilization of existing and recruitment of new neurons selective for these stimuli.