Biology subjects

Carandini, M.

Publications and source records attributed to Carandini, M..

At least 37 records · Page 2Linked to original sources

bioRxiv2023

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. 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 prior probability alternating between 0.2 and 0.8 in blocks of variable length. We found that mice estimate this prior probability and thereby improve their decision accuracy. Furthermore, we report that this subjective prior is encoded in at least 20% to 30% of brain regions which, remarkably, span all levels of processing, from early sensory areas (LGd, VISp) to motor regions (MOs, MOp, GRN) and high level cortical regions (ACAd, ORBvl). This widespread representation of the prior is consistent with a neural model of Bayesian inference involving loops between areas, as opposed to a model in which the prior is incorporated only in decision-making areas. This study offers the first brain-wide perspective on prior encoding at cellular resolution, underscoring the importance of using large scale recordings on a single standardized task.

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bioRxiv2023

Mouse frontal cortex nonlinearly encodes sensory, choice and outcome signals

Frontal area MOs (secondary motor area) is a key brain structure in rodents for making decisions based on sensory evidence and on reward value. In behavioral tasks, its neurons can encode sensory stimuli, upcoming choices, expected rewards, ongoing actions, and recent outcomes. However, the information encoded, and the nature of the resulting code, may depend on the task being performed. We recorded MOs population activity using two-photon calcium imaging, in a task requiring mice to integrate sensory evidence with reward value. Mice turned a wheel to report the location of a visual stimulus following a delay period, to receive a reward whose size varied over trial blocks. MOs neurons encoded multiple task variables, but not all of those seen in other tasks. In the delay period, the MOs population strongly encoded the stimulus side but did not significantly encode the reward-size block. A correlation of MOs activity with upcoming choice could be explained by a common effect of stimulus on those two correlates. After the wheel turn and the feedback, the MOs population encoded choice side and choice outcome jointly and nonlinearly according to an exclusive-or (XOR) operation. This nonlinear operation would allow a downstream linear decoder to infer the correct choice side (i.e., the side that would have been rewarded) even on zero contrast trials, when there had been no visible stimulus. These results indicate that MOs neurons flexibly encode some but not all variables that determine behavior, depending on task. Moreover, they reveal that MOs activity can reflect a nonlinear combination of these behavioral variables, allowing simple linear inference of task events that would not have been directly observable.

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bioRxiv2022

Visuomotor learning promotes visually evoked activity in the medial prefrontal cortex

The medial prefrontal cortex (mPFC) is necessary for executing many learned associations between stimuli and movement. It is unclear, however, whether activity in the mPFC reflects sensory or motor aspects of sensorimotor associations and whether it evolves gradually during learning. To address these questions, we recorded cortical activity with widefield calcium imaging while mice learned a visuomotor task. The task involved associating a visual stimulus with a forelimb movement. After learning, the mPFC showed stimulus-evoked activity both during task performance and during passive viewing, when the stimulus evoked no action. This stimulus-evoked activity closely tracked behavioral performance across training, exhibiting jumps between training days. Electrophysiological recordings localized this activity to the secondary motor and anterior cingulate cortex. We conclude that learning a visuomotor task promotes a route for visual information to reach the prefrontal cortex, which develops responses to the relevant visual stimuli even outside the context of the task.

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bioRxiv2021

A transcriptomic axis predicts state modulation of cortical interneurons

Transcriptomics has revealed the exquisite diversity of cortical inhibitory neurons1-7, but it is not known whether these fine molecular subtypes have correspondingly diverse activity patterns in the living brain. Here, we show that inhibitory subtypes in primary visual cortex (V1) have diverse correlates with brain state, but that this diversity is organized by a single factor: position along their main axis of transcriptomic variation. We combined in vivo 2-photon calcium imaging of mouse V1 with a novel transcriptomic method to identify mRNAs for 72 selected genes in ex vivo slices. We used transcriptomic clusters (t-types)4 to classify inhibitory neurons imaged in layers 1-3 using a three-level hierarchy of 5 Families, 11 Classes, and 35 t-types. Visual responses differed significantly only across Families, but modulation by brain state differed at all three hierarchical levels. Nevertheless, this diversity could be predicted from the first transcriptomic principal component, which predicted a cell types brain state modulation and correlations with simultaneously recorded cells. Inhibitory t-types with narrower spikes, lower input resistance, weaker adaptation, and less axon in layer 1 as determined in vitro8 fired more in resting, oscillatory brain states. Transcriptomic types with the opposite properties fired more during arousal. The former cells had more inhibitory cholinergic receptors, and the latter more excitatory receptors. Thus, despite the diversity of V1 inhibitory neurons, a simple principle determines how their joint activity shapes state-dependent cortical processing.

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bioRxiv2021

Behavioral origin of sound-evoked activity in visual cortex

Sensory cortices can be affected by stimuli of multiple modalities and are thus increasingly thought to be multisensory. For instance, primary visual cortex (V1) is influenced not only by images but also by sounds. Here we show that the activity evoked by sounds in V1 is highly stereotyped across neurons and even across mice. It resembles activity measured elsewhere in the brain and is independent of projections from auditory cortex. Its low-dimensional nature starkly contrasts the high dimensional code that V1 uses to represent images. Furthermore, this sound-evoked activity can be precisely predicted by small body movements that are elicited by each sound and are highly stereotyped across trials and across mice. Thus, neural activity that is apparently multisensory may simply arise from low-dimensional signals associated with changes in internal state and behavior.

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bioRxiv2021

Learning orthogonalizes visual cortical population codes

Training in behavioral tasks can alter visual cortical stimulus coding, but the precise form of this plasticity is unclear. We measured orientation tuning in 4,000-neuron populations of mouse V1 before and after training on a visuomotor task. Changes to single-cell tuning curves were apparently complex, including appearance of asymmetric and multi-peaked tuning curves. Nevertheless, these changes reflected a simple mathematical transformation of population activity, suppressing responses to motor-associated stimuli specifically in cells responding at intermediate levels. The strength of the transformation varied across trials, suggesting a dynamic circuit mechanism rather than static synaptic plasticity. This transformation resulted in sparsening and orthogonalization of population codes for motor-associated stimuli. Training did not improve the performance of an optimal stimulus decoder, which was already perfect even for naive codes, but the resulting orthogonalization improved the performance of a suboptimal decoder model with inductive bias as might be found in downstream readout circuits.

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bioRxiv2021

The role of frontal cortex in multisensory decisions

To make accurate perceptual decisions, the brain often combines information across sensory modalities. For instance, localizing objects by integrating their image and sound. However, the cortical substrates underlying this audiovisual integration remain uncertain. Here, we show that mouse frontal cortex combines auditory and visual evidence; that this combination is additive, mirroring behavior; and that it evolves with learning. Scanning optogenetic inactivation demonstrated that inactivating frontal cortex impaired choices based on either sensory modality. Recordings from >10,000 neurons indicated that after task learning, activity in frontal area MOs (secondary motor cortex) encodes an additive combination of visual and auditory signals, consistent with the mices behavioral strategy. An accumulator model applied to these sensory representations reproduced both the observed choices and reaction times. These results indicate that frontal cortex adapts through learning to combine evidence across sensory cortices, providing a signal that is transformed into a binary decision by a downstream accumulator.

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bioRxiv2021

Neural basis of functional ultrasound signals

Functional ultrasound imaging (fUSI) is a popular method for measuring blood flow and thus infer brain activity, but it relies on the physiology of neurovascular coupling and requires extensive signal processing. To establish to what degree its trial-by-trial signals reflect neural activity, we performed simultaneous fUSI and neural recordings with Neuropixels probes in awake mice. fUSI signals strongly correlated with the slow (<0.3 Hz) fluctuations in local firing rate, and were closely predicted by the smoothed firing rate of local neurons, particularly putative inhibitory neurons. The optimal smoothing filter had width ~3 s, matched the hemodynamic response function of awake mouse, was invariant across mice and stimulus conditions, and similar in cortex and hippocampus. fUSI signals also matched neural firing spatially: firing rates were as highly correlated across hemispheres as fUSI signals. Thus, hemodynamic signals measured by ultrasound bear a simple and accurate relationship to neuronal firing.

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bioRxiv2020

Task specificity in mouse parietal cortex

Parietal cortex is implicated in a variety of behavioral processes, but it is unknown whether and how individual neurons participate in multiple tasks. We trained head-fixed mice to perform two visual decision tasks involving a steering wheel or a virtual T-maze, and recorded from the same parietal neurons during the two. Neurons that were active during the T-maze task were typically inactive during the steering-wheel task, and vice versa. Recording from the same neurons in the same apparatus without task stimuli yielded the same specificity as in the task, suggesting that task specificity depends on physical context. To confirm this, we trained some mice in a third task combining the steering wheel with the visual environment of the T-maze. This hybrid task engaged the same neurons as the steering-wheel task. Thus, participation by neurons in mouse parietal cortex is task-specific, and this specificity is determined by physical context.

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bioRxiv2020

Neuropixels 2.0: A miniaturized high-density probe for stable, long-term brain recordings

To study the dynamics of neural processing across timescales, we require the ability to follow the spiking of thousands of individually separable neurons over weeks and months, during unrestrained behavior. To address this need, we introduce the Neuropixels 2.0 probe together with novel analysis algorithms. The new probe has over 5,000 sites and is miniaturized such that two probes plus a headstage, recording 768 sites at once, weigh just over 1 g, suitable for implanting chronically in small mammals. Recordings with high quality signals persisting for at least two months were reliably obtained in two species and six different labs. Improved site density and arrangement combined with new data processing methods enable automatic post-hoc stabilization of data despite brain movements during behavior and across days, allowing recording from the same neurons in the mouse visual cortex for over 2 months. Additionally, an optional configuration allows for recording from multiple sites per available channel, with a penalty to signal-to-noise ratio. These probes and algorithms enable stable recordings from >10,000 sites during free behavior in small animals such as mice.

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bioRxiv2020

Dopamine axons to dorsal striatum encode contralateral stimuli and actions

Midbrain dopamine neurons play key roles in decision-making by regulating reward valuation and actions. These roles are thought to depend on dopamine neurons innervating striatum. In addition to actions and rewards, however, efficient decisions often involve consideration of uncertain sensory signals. The functions of striatal dopamine during sensory decisions remains unknown. We trained mice in a task that probed decisions based on sensory evidence and reward value, and recorded the activity of striatal dopamine axons. Dopamine axons in ventral striatum (VS) responded to bilateral stimuli and trial outcomes, encoding prediction errors that scaled with decision confidence and reward value. By contrast, dopamine axons in dorsal striatum (DS) responded to contralateral stimuli and contralateral actions. Thus, during sensory decisions, striatal dopamine signals are anatomically organized. VS dopamine resembles prediction errors suitable for reward maximization under sensory uncertainty whereas DS dopamine encodes specific combinations of stimuli and actions in a lateralized fashion.

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bioRxiv2020

Equations governing dynamics of excitation and inhibition in the mouse corticothalamic network

Although cortical circuits are complex and interconnected with the rest of the brain, their macroscopic dynamics are often approximated by modeling the averaged activities of excitatory and inhibitory cortical neurons, without interactions with other brain circuits. To verify the validity of such mean-field models, we optogenetically stimulated populations of excitatory and parvalbumin-expressing inhibitory neurons in awake mouse visual cortex, while recording population activity in cortex and in its thalamic correspondent, the lateral geniculate nucleus. The cortical responses to brief test pulses could not be explained by a mean-field model including only cortical excitatory and inhibitory populations. However, these responses could be predicted by extending the model to include thalamic interactions that cause net cortical suppression following activation of cortical excitatory neurons. We conclude that mean-field models can accurately summarize cortical dynamics, but only when the cortex is considered as part of a dynamic corticothalamic network.

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bioRxiv2020

A standardized and reproducible method to measure 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. We designed a task for head-fixed mice that combines established assays of perceptual and value-based decision making, and we standardized training protocol and experimental hardware, software, and procedures. We trained 140 mice across seven laboratories in three countries, and we collected 5 million mouse choices into a publicly available database. Learning speed was variable across mice and laboratories, but once training was complete there were no significant differences in behavior across laboratories. Mice in different laboratories adopted similar reliance on visual stimuli, on past successes and failures, and on estimates of stimulus prior probability to guide their choices. These results reveal that a complex mouse behavior can be successfully reproduced across multiple laboratories. They establish a standard for reproducible rodent behavior, and provide an unprecedented dataset and open-access tools to study decision-making in mice. More generally, they indicate a path towards achieving reproducibility in neuroscience through collaborative open-science approaches.

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bioRxiv2019

Spatial encoding in the visual pathway arises in cortex and depends on active navigation

During navigation, the visual responses of neurons in primary visual cortex (V1) are modulated by the animals spatial position. Here we show that this spatial modulation is similarly present across multiple higher visual areas but largely absent in the main thalamic pathway into V1. Similar to hippocampus, spatial modulation in visual cortex strengthens with experience and requires engagement in active behavior. Active navigation in a familiar environment, therefore, determines spatial modulation of visual signals starting in the cortex.

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bioRxiv2019

Striatal activity reflects cortical activity patterns

The dorsal striatum is organized into domains that drive characteristic behaviors1-7, and receive inputs from different parts of the cortex8,9 which modulate similar behaviors10-12. Striatal responses to cortical inputs, however, can be affected by changes in connection strength13-15, local striatal circuitry16,17, and thalamic inputs18,19. Therefore, it is unclear whether the pattern of activity across striatal domains mirrors that across the cortex20-23 or differs from it24-28. Here we use simultaneous large-scale recordings in the cortex and the striatum to show that striatal activity can be accurately predicted by spatiotemporal activity patterns in the cortex. The relationship between activity in the cortex and the striatum was spatially consistent with corticostriatal anatomy, and temporally consistent with a feedforward drive. Each striatal domain exhibited specific sensorimotor responses that predictably followed activity in the associated cortical regions, and the corticostriatal relationship remained unvaried during passive states or performance of a task probing visually guided behavior. However, the tasks visual stimuli and corresponding behavioral responses evoked relatively more activity in the striatum than in associated cortical regions. This increased striatal activity involved an additive offset in firing rate, which was independent of task engagement but only present in animals that had learned the task. Thus, striatal activity largely reflects patterns of cortical activity, deviating from them in a simple additive fashion for learned stimuli or actions.

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bioRxiv2019

RIGBOX: AN OPEN-SOURCE TOOLBOX FOR PROBING NEURONS AND BEHAVIOR

Setting up an experiment in behavioral neuroscience is a complex process that is often managed with ad hoc solutions. To streamline this process we developed Rigbox, a high-performance, open-source software toolbox that facilitates a modular approach to designing experiments (github.com/cortex-lab/Rigbox). Rigbox simplifies hardware I/O, synchronizes data streams from multiple sources, communicates with remote databases, and implements visual and auditory stimuli presentation. Its main submodule, Signals, allows intuitive programming of behavioral tasks. Here we illustrate its function with two interactive examples: a human psychophysics experiment, and the game of Pong. We give an overview of the other packages in Rigbox, provide benchmarks, and conclude with a discussion on the extensibility of the software and comparisons with similar toolboxes. Rigbox runs in MATLAB, with Java components to handle network communication, and a C library to boost performance.

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bioRxiv2019

Retinal outputs depend on behavioural state

The operating mode of the visual system depends on behavioural states such as arousal1,2. This dependence is seen both in primary visual cortex3-7 (V1) and in subcortical brain structures receiving direct retinal input4,8. Here we show that this effect arises as early as in the output of the retina. We first measured activity in a region that receives retinal projections9, the superficial superior colliculus (sSC), and found that this activity strongly depended on behavioural state. This modulation was not mediated by feedback inputs from V1 as it was immune to V1 inactivation. We then used Neuropixels probes10 to record activity in the optic tract, and we found some retinal axons whose activity significantly varied with arousal, even in darkness. To characterize these effects on a larger sample of retinal outputs, we imaged the activity of retinal boutons11,12 in sSC during behaviour using a calcium indicator. The activity of these boutons correlated with arousal as strongly as that of sSC neurons, and this correlation persisted also during darkness. These results reveal a novel property of retinal function in mice, which could be observed only during behaviour: retinal outputs are modulated by behavioural state before they reach the rest of the brain.

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bioRxiv2019

Modulation of visual cortex by hippocampal signals

Neurons in primary visual cortex (V1) are influenced by the animals position in the environment and encode positions that correlate with those encoded by hippocampus (CA1). Might V1s encoding of spatial positions be inherited from hippocampal regions? If so, it should depend on non-visual factors that affect the encoding of position in hippocampus, such as the physical distance traveled and the phase of theta oscillations. We recorded V1 and CA1 neurons while mice ran through a virtual corridor and confirmed these predictions. Spatial representations in V1 and CA1 were correlated even in the absence of visual cues. Moreover, similar to CA1 place cells, the spatial responses of V1 neurons were influenced by the physical distance traveled and the phase of hippocampal theta oscillations. These results reveal a modulation of cortical sensory processing by non-sensory estimates of position that might originate in hippocampal regions.

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