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During perceptually guided decisions, correlates of choice are found as upstream as in the primary sensory areas. However, how well these choice signals align with early sensory representations, a prerequisite for their interpretation as feedforward substrates of perception, remains an open question. We designed a two alternative forced choice task (2AFC) in which male mice compared stimulation frequencies applied to two adjacent vibrissae. The optogenetic silencing of individual columns in the primary somatosensory cortex (wS1) resulted in predicted shifts of psychometric functions, demonstrating that perception depends on focal, early sensory representations. Functional imaging of layer II/III single neurons revealed mixed coding of stimuli, choices and engagement in the task. Neurons with multi-whisker suppression display improved sensory discrimination and had their activity increased during engagement in the task, enhancing selectively representation of the signals relevant to solving the task. From trial to trial, representation of stimuli and choice varied substantially, but mostly orthogonally to each other, suggesting that perceptual variability does not originate from wS1 fluctuations but rather from downstream areas. Together, our results highlight the role of primary sensory areas in forming a reliable sensory substrate that could be used for flexible downstream decision processes. It is an open question whether choice signals in primary sensory areas have a causal influence on an animal’s perception. Here, the authors show that early sensory representations in the neocortex can be selectively manipulated to bias perception during discrimination behavior.

The authors explore how sensory maps are reshaped by experience in vivo , using chronic two-photon calcium imaging to follow whisker-evoked activity of individual layer 2/3 neurons in adult mouse barrel cortex over weeks. By first measuring activity with whiskers intact and then with continued trimming of all but one whisker, they describe how the redistribution of population activity underlies large-scale cortical remapping. Sensory maps are reshaped by experience. It is unknown how map plasticity occurs in vivo in functionally diverse neuronal populations because activity of the same cells has not been tracked over long time periods. Here we used repeated two-photon imaging of a genetic calcium indicator to measure whisker-evoked responsiveness of the same layer 2/3 neurons in adult mouse barrel cortex over weeks, first with whiskers intact, then during continued trimming of all but one whisker. Across the baseline period, neurons displayed heterogeneous yet stable responsiveness. During sensory deprivation, responses to trimmed whisker stimulation globally decreased, whereas responses to spared whisker stimulation increased for the least active neurons and decreased for the most active neurons. These findings suggest that recruitment of inactive, 'silent' neurons is part of a convergent redistribution of population activity underlying sensory map plasticity. Sensory-driven responsiveness is a key property controlling experience-dependent activity changes in individual neurons.

In rodents, descending corticospinal tracts can be rerouted to innervate new targets after a spinal cord injury. Here, Ghosh et al . show that such anatomical rearrangement in the injured spinal cord is accompanied by sensory remapping at the cortical level. Little is known about the functional role of axotomized cortical neurons that survive spinal cord injury. Large thoracic spinal cord injuries in adult rats result in impairments of hindlimb function. Using retrograde tracers, we found that axotomized corticospinal axons from the hindlimb sensorimotor cortex sprouted in the cervical spinal cord. Mapping of these neurons revealed the emergence of a new forelimb corticospinal projection from the rostral part of the former hindlimb cortex. Voltage-sensitive dye (VSD) imaging and blood-oxygen-level–dependent functional magnetic resonance imaging (BOLD fMRI) revealed a stable expansion of the forelimb sensory map, covering in particular the former hindlimb cortex containing the rewired neurons. Therefore, axotomised hindlimb corticospinal neurons can be incorporated into the sensorimotor circuits of the unaffected forelimb.

Pupillometry, the measure of pupil size and reactivity, has been widely used to assess cognitive processes. As such, changes in pupil size have been shown to correlate with arousal, locomotion, cortical state and decision-making processes. In addition, pupillary responses have been linked to the activity of neuromodulatory systems that modulate attention and perception as the noradrenergic and cholinergic systems. Due to the extent of processes the pupil reflects, we aimed at resolving pupillary responses in context of behavioral state and task performance while recording pupillary transients of mice performing a vibrotactile two-alternative forced choice task (2-AFC). We show that pre-stimulus pupil size differentiates between states of disengagement from task performance versus active engagement. In addition, when actively engaged, post-stimulus, pupillary dilations for correct responses are larger than for error responses with this difference reflecting response confidence. Importantly, in a delayed 2-AFC task version, we show that even though pupillary transients mainly reflect motor output or reward anticipation following the response of the animal, they also reflect animal decision confidence prior to its response. Finally, in a condition of passive engagement, when stimulus has no task relevance with reward provided automatically, pupillary dilations reflect stimulation and reward being reduced relative to a state of active engagement explained by shifts of attention from task variables. Our results provide extensive evidence that in addition to reflecting attentiveness under task performance, pupil dilations also reflect the confidence of the subject in his ensuing response. This confidence coding is overlaid within a more pronounced pupil dilation that reflects motor output or other post-decision components that are related to the response itself but not to the decision. Our results also provide evidence how different behavioral states, imposed by task demands, modulate what the pupil is reflecting, presumably showing what the underlying cognitive network is coding for.

During adaptation, neocortical responses change as a result of repeated sensory stimulation, but it's unclear how this affects perception. Here the authors use optogenetics to mimic sensory evoked cortical responses with or without adaptation. They find adaptation impairs frequency discrimination but enhances change detection during whisker stimulation. Neocortical responses typically adapt to repeated sensory stimulation, improving sensitivity to stimulus changes, but possibly also imposing limitations on perception. For example, it is unclear whether information about stimulus frequency is perturbed by adaptation or encoded by precise response timing. We addressed this question in rat barrel cortex by comparing performance in behavioral tasks with either whisker stimulation, which causes frequency-dependent adaptation, or optical activation of cortically expressed channelrhodopsin-2, which elicits non-adapting neural responses. Circumventing adaption by optical activation substantially improved cross-hemispheric discrimination of stimulus frequency. This improvement persisted when temporal precision of optically evoked spikes was reduced. We were able to replicate whisker-driven behavior only by applying adaptation rules mimicking sensory-evoked responses to optical stimuli. Conversely, in a change-detection task, animals performed better with whisker than optical stimulation. Our results directly demonstrate that sensory adaptation critically governs the perception of stimulus patterns, decreasing fidelity under steady-state conditions in favor of change detection.

The rodent whisker system is a preferred model for studying plasticity in the somatosensory cortex (barrel cortex). Contrarily, only a small amount of research has been conducted to characterize the stability of neuronal population activity in the barrel cortex. We used the mouse whisker system to address the neuronal basis of stable perception in the somatosensory cortex. Cortical representation of periodic whisker deflections was studied in populations of neurons in supragranular layers over extended time periods (up to 3months) with long-term two-photon Ca2+ imaging in anesthetized mice. We found that in most of the neurons (87%), Ca2+ responses increased sublinearly with increasing number of contralateral whisker deflections. The imaged population of neurons was activated in a stereotypic way over days and for different deflection rates (pulse frequencies). Thus, pulse frequencies are coded by response strength rather than by distinct neuronal sub-populations. A small population of highly responsive neurons (~3%) was sufficient to decode the whisker stimulus. This conserved functional map, led by a small set of highly responsive neurons, might form the foundation of stable sensory percepts. •Cortical representation of whisker deflection frequencies was stable over weeks.•Ca2+ responses increased sublinearly with increasing number of whisker deflections.•Deflection frequency was decoded by a small fraction of the population (~3%).•Pulse frequency was reflected by response amplitude of identical neuronal ensembles.

Conventional decoding methods in neuroscience aim to predict discrete brain states from multivariate correlates of neural activity. This approach faces two important challenges. First, a small number of examples are typically represented by a much larger number of features, making it hard to select the few informative features that allow for accurate predictions. Second, accuracy estimates and information maps often remain descriptive and can be hard to interpret. In this paper, we propose a model-based decoding approach that addresses both challenges from a new angle. Our method involves (i) inverting a dynamic causal model of neurophysiological data in a trial-by-trial fashion; (ii) training and testing a discriminative classifier on a strongly reduced feature space derived from trial-wise estimates of the model parameters; and (iii) reconstructing the separating hyperplane. Since the approach is model-based, it provides a principled dimensionality reduction of the feature space; in addition, if the model is neurobiologically plausible, decoding results may offer a mechanistically meaningful interpretation. The proposed method can be used in conjunction with a variety of modelling approaches and brain data, and supports decoding of either trial or subject labels. Moreover, it can supplement evidence-based approaches for model-based decoding and enable structural model selection in cases where Bayesian model selection cannot be applied. Here, we illustrate its application using dynamic causal modelling (DCM) of electrophysiological recordings in rodents. We demonstrate that the approach achieves significant above-chance performance and, at the same time, allows for a neurobiological interpretation of the results.

β+-sensitive probes are useful tools for the measurement of radiotracer kinetics in small animals. They allow the cost-effective development of new PET tracers and offer the possibility to investigate a variety of cerebral processes. The study's main aim was the in vivo evaluation of a probe system for cerebral surface acquisitions. The detector system is a 0.2-mm thick scintillating disk of 3-mm diameter, positioned close to the cerebral surface. The study consists of 4 subparts: (1) simulation of the detection volume, (2) direct comparison with the classic intracortical beta probe regarding its capability to acquire kinetic data, (3) test of the ability to detect local tracer accumulations during infraorbital nerve (ION) electrostimulation and (4) demonstration of the feasibility to measure tracer kinetics in awake animals. Kinetic data acquired with 18F-fluorodeoxyglucose and 15O-H2O were fitted with standard compartment models. The surface probe measurements were in good agreement with those obtained using the intracortical scintillator. ION electrostimulation induced a marked increase in tracer accumulation adequately detected by the surface probe. In the head-fixed animal, a marked change in FDG kinetics was detected between the awake and anesthetized state. The novel surface probe system proved to be a valuable instrument for in vivo radiotracer studies of the cerebral cortex. Its main advantage is the absence of any tissue damage. In addition, serial acquisitions of tracer kinetics in the awake animal turned out to be feasible.

During perceptually guided decisions, correlates of choice are found as upstream as in the primary sensory areas. However, how well these choice signals align with early sensory representations, a prerequisite for their interpretation as feedforward substrates of perception, remains an open question. We designed a two alternative forced choice task (2AFC) in which mice compared stimulation frequencies applied to two adjacent vibrissae. The optogenetic silencing of individual columns in the primary somatosensory cortex (wS1) resulted in predicted shifts of psychometric functions, demonstrating that perception depends on focal, early sensory representations. Functional imaging of layer II/III single neurons revealed sensory, choice and engagement coding. From trial to trial, these three varied substantially, but independently from one another. Thus, coding of sensory and non-sensory variables co-exist in orthogonal subspace of the population activity, suggesting that perceptual variability does not originate from wS1 but rather from state or choice fluctuations in downstream areas.

Pupillometry, the measure of pupil size and reactivity, has been widely used to assess cognitive processes. As such, changes in pupil size have been shown to correlate with arousal, locomotion, cortical state and decision-making processes. In addition, pupillary responses have been linked to the activity of neuromodulatory systems that modulate attention and perception as the noradrenergic and cholinergic systems. Due to the extent of processes reflected by the pupil, we aimed at resolving pupillary responses in context of behavioral state and task performance while recording pupillary transients of mice performing a vibrotactile two-alternative forced choice task (2-AFC). We show that pre-stimulus pupil size differentiates between states disengagement from task performance versus when actively engaged. In addition, when actively engaged, post-stimulus, pupillary dilations for correct responses are larger than for error responses with this difference reflecting response confidence. Importantly, in a delayed 2-AFC task we show that even though pupillary transients mainly reflect motor output following the response of the animal, they also reflect animal decision confidence prior to its response. Finally, in a condition of passive engagement, when stimulus has no task relevance with reward provided automatically, pupillary dilations rather reflect stimulation and reward and are reduced relative to a state of active engagement explained by shifts of attention from irrelevant task occurrences. Our results provide further evidence of how pupillary dilations reflect cognitive processes in a task relevant context, showing that the pupil reflects response confidence and baseline pupil size encodes attentiveness rather than general arousal. Footnotes * Cosmetic revision. typos