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Pennartz, C. M. A.

Publications and source records attributed to Pennartz, C. M. A..

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Neuroline: an integrated modular pipeline for FAIR multimodal neurophysiology data processing

The adoption of FAIR principles for code and data sharing in systems neuroscience is hindered by the size and diversity of datasets, the multitude of data formats and the complexity of analysis workflows. These challenges have led to the development of various data standards and modality-specific processing and analysis tools. However, it remains difficult to integrate the diverse processed data streams originating from state-of-the-art neurophysiology experiments into a common format, which is crucial for cross-modal analyses and open, FAIR sharing of data. To address this, we developed Neuroline, a Python package for processing neurophysiology data (electrophysiology, optical imaging, and behaviour) that combines multimodal integration, modularity, and standardised output within a single pipeline. It leverages established packages and consolidates the resulting processed data into the standardised Neurodata Without Borders (NWB) format. Neuroline provides a unified interface while preserving flexibility and extensibility. Here we describe the implementation and challenges of a pipeline capable of integrating different types of neuroscientific data and packages. Finally, we address how Neuroline contributes to the sustainability and accessibility of neuroscience data and software.

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Behavioral arousal organizes visual cortical population micro-states across the sleep-wake cycle

Brain states are conventionally defined as discrete categories, such as wakefulness, NREM sleep and REM sleep. Yet, whether these labels fully capture the organization of cortical population dynamics remains unclear. Using large-field-of-view two-photon calcium imaging of layer II/III pyramidal neurons in mouse primary visual cortex (V1), we show that population activity organizes into recurring micro-states that span conventional sleep-wake boundaries. A Hidden Markov Model fitted independently of behavioral state labels identified temporally stable micro-states with structured transition pathways. Micro-state organization was more strongly aligned with a continuous behavioral arousal axis, indexed by pupil diameter and orofacial motion, than with discrete NREM-wake categories, a relationship confirmed by mediation analysis. At the circuit level, two spatially intermingled but functionally opposing neuronal ensembles tracked this arousal axis in opposite directions. These findings establish behavioral arousal, rather than discrete wake-sleep state, as the primary organizing dimension of V1 population dynamics.

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Sound-evoked orofacial motion only affects a fraction of visually responsive V1 neurons in a multisensory detection task with delayed reward delivery

Auditory stimuli have been known to elicit neural responses in visual cortical areas, but such responses are partly associated with sound-evoked orofacial movements. However, it remains unclear to what extent neural correlates of movement can be dissociated from non-motor correlates. Here we developed a paradigm with a forced delayed-response mechanism by means of a moving reward apparatus in order to test whether this results in low amounts of movement-related neural activity shortly after stimulus onset. Animals performed a multisensory detection task, while we recorded neural activity from V1 and measured orofacial motion. During the delay, when only the stimulus was present, orofacial motion was relatively low. Reward-related motion increased after the delay, with a concomitant increase in motor-related spiking activity. Visual stimulation did neither elicit considerable motion nor corresponding neural responses in the delay period. Conversely, salient auditory stimuli led to modest, but increased orofacial motion and related neuronal activity during the delay. We identified a subpopulation of visually responsive V1 neurons that did not show correlations with orofacial movement, with only the stimulus being represented. These results present a forced delayed-response window as a method to help disentangle motor-related activity from visual (but not auditory) processing and show that motor-related activity only affects a fraction of visually selective neurons.

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Switches in Orientation Coding by Mouse Primary Visual Cortex Neurons Depend on Stimulus Predictability.

How the brain processes a stimulus depends on contextual factors, such as whether it is predictable or surprising. While this process has been partially characterized using EEG and fMRI, and invasive cellular approaches, the microcircuit mechanisms responsible for comparing sensory input and expectations remain poorly understood. Here, we combined layer-resolved recordings of single-unit activity and local field potentials (LFP) in mouse primary visual cortex (V1) with a visual oddball paradigm using oriented gratings. Both event-related potentials and firing rates exhibited distinct temporal components across cortical layers and trial types. We identified robust stimulus-specific adaptation (SSA), mismatch negativity (MMN), and deviant detection (DD) contrast at both early and late epochs. Surprisingly, a substantial subset of excitatory neurons exhibited complete reversals of orientation preference ("preference switches") between standard and deviant trials, rather than only changes in selectivity. These preference-switching cells were primarily observed in layers 2/3 and 5/6 and contributed as much information to stimulus decoding as stably tuned neurons. Our findings demonstrate that context-dependent flexibility in feature preference is an integral part of predictive coding in V1 and challenge the notion of fixed stimulus representations at the single-neuron level.

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A polymeric, PDMS-based large-scale skull replacement suitable for optical and mechanical access for long-term neuronal imaging, electrophysiology, and optogenetics

Many techniques to record and manipulate neuronal activity across large portions of the vertebrate brain, such as widefield and two-photon calcium imaging, electrophysiology, and optogenetics, are now available. However, few effective approaches enable both optical and mechanical access to the brain. In this work, we offer an in-depth guide for synthesizing, implanting, and using polydimethylsiloxane (PDMS) windows as skull replacements for chronic optical neuronal imaging. Furthermore, we provide instructions to perform viral injections and multi-site silicon probe implantation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/648966v1_ufig1.gif" ALT="Figure 1"> View larger version (71K): org.highwire.dtl.DTLVardef@1900a2dorg.highwire.dtl.DTLVardef@18c436corg.highwire.dtl.DTLVardef@19e6a4corg.highwire.dtl.DTLVardef@154c228_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO C_FIG

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A computational architecture incorporating shallow brain networks: integrating parallel cortical and subcortical processing

Artificial neural networks commonly have deep hierarchical structures that were originally inspired by the neuroanatomical evidence of cortico-cortical connectivity pattern found in the mammalian brain. Largely neglected in those models are non-hierarchical aspects of brain architecture, namely the subcortical pathways and the interactions between cortical and subcortical areas regardless of their hierarchical locations. Inspired by this principle, we present a computational model combining cortical hierarchical processing with subcortical pathways based on neuroanatomical evidence. We show the versatility of our model by implementing the cortical hierarchy in two alternative ways--a convolutional feedforward network and a predictive coding network. Both model variants can replicate behavioral observations in humans and monkeys on a perceptual context-dependent decision-making task. The model also reveals that subcortical structures lead decisions for easy trials while the more complex hierarchical network is necessary for the harder trials. Our results suggest that the parallel cortico-subcortical processing explored in the model represents a fundamental property that cannot be neglected in understanding the computational principles used by the brain. SignificanceArtificial intelligence and computational neuroscience models, particularly deep learning and predictive coding architectures, have been traditionally dominated by cortico-centric hierarchical frameworks. However, extensive neurobiological evidence suggests that cortical areas, regardless of their hierarchical classification, are deeply interconnected with subcortical structures in real brains. We propose here a computational framework demonstrating that parallel cortical-subcortical architectures can yield complex and more flexible computational capabilities, aligning with the observed behavior in the mammalian brain. Our model addresses key limitations in existing deep learning and predictive coding networks, offering a more biologically plausible and functionally advantageous alternative.

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Cell type specific firing patterns in a V1 cortical column model depend on feedforward and feedback activity

Stimulation of specific cell groups under different network regimes (e.g., spontaneous activity or sensory-evoked activity) can provide insights into the neural dynamics of cortical columns. While these protocols are challenging to perform experimentally, modelling can serve as a powerful tool for such explorations. Using detailed electrophysiological and anatomical data from mouse V1, we built a novel spiking network model of a cortical column, which incorporates pyramidal cells and three distinct interneuron types (PV, SST, and VIP cells, specified per lamina), as well as the dynamic and voltage-dependent properties of AMPA, GABA, and NMDA receptors. We first demonstrate that thalamocortical feedforward (FF) and feedback (FB) stimuli arriving in the column have opposite effects, leading to net columnar excitation and inhibition respectively and revealing translaminar gain control via full-column inhibition by layer 6. We then perturb one cell group (i.e. a cell type in a specific layer) at a time and observe the effects on other cell groups under distinct network states: spontaneous, feedforward-driven, feedback-driven, and a combination of feedforward and feedback. Our findings reveal that when a given group is perturbed, the columnar response varies significantly based on its state, with strong sensory feedforward input decreasing columnar sensitivity to all perturbations and feedback input serving as modulator of intra columnar interactions. Given that activity changes within specific neuronal populations are difficult to predict a priori in experiments, our model may constitute a useful tool to predict outcomes of perturbations and assist in experimental design. Author SummaryIn this study, we explored how stimulating specific groups of neurons under different conditions (spontaneous or stimulus-evoked states) can help us understand the dynamics of visual cortical columns in mouse cortex. We developed a data-constrained model of a cortical column that includes several cell types (excitatory neurons as well as multiple inhibitory neuron types) and synaptic receptors. Our findings reveal that signals coming from higher brain areas (feedback input) and sensory input (feedforward input) have different impacts on the column: sensory inputs generally increase activity within the column, while feedback tends to decrease it. We then considered input targeting one cell type at a time to see how it affects the internal dynamics. Our results show that neural responses to selected input vary depending on whether the cortical column is in a resting state or being stimulated by feedforward input or feedback input. This model is a useful tool for predicting the outcomes of these cell interactions, which can help in planning real-world experiments and understanding how our brain processes information.

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Increased perceptual reliability reduces membrane potential variability in cortical neurons

Uncertainty is omnipresent. While humans and other animals take uncertainty into account during decision making, it remains unclear how it is represented in cortex. To investigate the effect of stimulus reliability on uncertainty representation in cortical neurons, we analyzed single unit activity data recorded in mouse PPC, while animals performed a multisensory change detection task. We further used simulation-based inference (SBI) to infer membrane potential statistics underlying the spiking activity. Our analysis shows that stimulus changes increase spiking rate while decreasing its variability. The inferred membrane potential statistics suggest that PPC neurons decrease their membrane potential variability in response to task relevant stimuli. Furthermore, more perceptually reliable stimuli lead to a larger decrease in membrane potential variability than less reliable ones. These findings suggest that individual cortical neurons track uncertainty, providing Bayesian benefits for downstream computations.

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Diverse and flexible behavioral strategies arise in recurrent neural networks trained on multisensory decision making

Behavioral variability across individuals leads to substantial performance differences during cognitive tasks, although its neuronal origin and mechanisms remain elusive. Here we use recurrent neural networks trained on a multisensory decision-making task to investigate inter-subject behavioral variability. By uniquely characterizing each network with a random synaptic-weights initialization, we observed a large variability in the level of accuracy, bias and decision speed across these networks, mimicking experimental observations in mice. Performance was generally improved when networks integrated multiple sensory modalities. Additionally, individual neurons developed modality-, choice- or mixed-selectivity, these preferences were different for excitatory and inhibitory neurons, and the concrete composition of each network reflected its preferred behavioral strategy: fast networks contained more choice- and mixed-selective units, while accurate networks had relatively less choice-selective units. External modulatory signals shifted the preferred behavioral strategies of networks, suggesting an explanation for the recently observed within-session strategy alternations in mice.

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Synaptic plasticity is required for oscillations in a V1 cortical column model with multiple interneuron types

Neural rhythms are ubiquitous in cortical recordings, but it is unclear whether they emerge due to the basic structure of cortical microcircuits, or depend on function. Using detailed electrophysiological and anatomical data of mouse V1, we explored this question by building a spiking network model of a cortical column incorporating pyramidal cells, PV, SST and VIP inhibitory interneurons, and dynamics for AMPA, GABA and NMDA receptors. The resulting model matched in vivo cell-type-specific firing rates for spontaneous and stimulus-evoked conditions in mice, although rhythmic activity was absent. Upon introduction of long-term synaptic plasticity in the form of an STDP rule, broad-band (15-60 Hz) oscillations emerged, with feedforward/feedback input streams enhancing/suppressing the oscillatory drive, respectively. These plasticity-triggered rhythms relied on all cell types, and specific experience-dependent connectivity patterns were required to generate oscillations. Our results suggest that neural rhythms are not necessarily intrinsic properties of cortical circuits, but rather they may arise from structural changes elicited by learning-related mechanisms.

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Local minimization of prediction errors drives learning of invariant object representations in a generative network model of visual perception

The ventral visual processing hierarchy of the cortex needs to fulfill at least two key functions: Perceived objects must be mapped to high-level representations invariantly of the precise viewing conditions, and a generative model must be learned that allows, for instance, to fill in occluded information guided by visual experience. Here, we show how a multilayered predictive coding network can learn to recognize objects from the bottom up and to generate specific representations via a top-down pathway through a single learning rule: the local minimization of prediction errors. Trained on sequences of continuously transformed objects, neurons in the highest network area become tuned to object identity invariant of precise position, comparable to inferotemporal neurons in macaques. Drawing on this, the dynamic properties of invariant object representations reproduce experimentally observed hierarchies of timescales from low to high levels of the ventral processing stream. The predicted faster decorrelation of error-neuron activity compared to representation neurons is of relevance for the experimental search for neural correlates of prediction errors. Lastly, the generative capacity of the network is confirmed by reconstructing specific object images, robust to partial occlusion of the inputs. By learning invariance from temporal continuity within a generative model, despite little change in architecture and learning rule compared to static input- reconstructing Hebbian predictive coding networks, simply by shifting the training paradigm to dynamic inputs, the approach generalizes the predictive coding framework to dynamic inputs in a more biologically plausible way than self-supervised networks with non-local error-backpropagation. Author SummaryNeurons in the inferotemporal cortex of primates respond to images of complex objects independent of position, rotational angle, or size. While feedforward models of visual perception such as deep neural networks can explain this, they fail to account for the use of top-down information, for example when sensory evidence is scarce. Here, we address the question of how the neuronal networks in the brain learn both bottom-up and top-down processing without labels as they are used in the artificial supervised learning paradigm. Building on previous work that explains vision as a process of iteratively improving predictions, learning in the predictive coding network is driven by the local minimization of prediction errors. When trained on sequences of moving inputs, the network learns both invariant high-level representations comparable to those in the inferotemporal cortex of primates, and a generative model capable of reconstructing whole objects from partially occluded input images in agreement with experimental recordings from early visual areas. Advancing the search for experimental hallmarks of prediction errors, we find that error neurons in the higher areas of the network change their activity on a shorter timescale than representation neurons.

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Triple dissociation of visual, auditory and motor processing in primary visual cortex

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.

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Spontaneous Variations in Arousal Modulate Subsequent Visual Processing and Local Field Potential Dynamics in the Ferret during Quiet Wakefulness

Behavioral states affect neuronal responses throughout the cortex and influence visual processing. Quiet wakefulness (QW) is a behavioral state during which subjects are quiescent, but awake and connected to the environment. Here, we examined the effects of pre-stimulus arousal variability on post-stimulus neural activity in primary visual cortex (V1) and posterior parietal cortex (PPc) in awake ferrets, using the pupil diameter as an indicator of arousal. We observed that during low arousal, low- frequency power increases during visual stimulation, and that the peak alpha frequency shifted depending on the arousal state. High arousal increased gamma power as well as low-frequency inter- and intra-areal coherence. Using a simplified model of laminar circuits, we show that this connectivity pattern is compatible with feedback signals targeting infragranular layers in area PPc and supragranular layers in V1. Neurons in V1 displayed higher firing rates at their preferred orientations on high-arousal trials. Broad-spiking cells in V1 entrained to high-frequency oscillations (>80 Hz), whereas narrow-spiking neurons phase-locked to low (12-18 Hz) and high-frequency (>80 Hz) rhythms. These results indicate that the variability and sensitivity of post-stimulus cortical responses and coherence depend on the pre-stimulus behavioral state and account for the neuronal response variability observed during repeated stimulation.

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Coherent mapping of position and head direction across auditory and visual cortex

Neurons in primary visual cortex (V1) may not only signal current visual input but also relevant contextual information such as reward expectancy and the subjects 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 subjects sensory-specific location. These may provide a common reference frame for distributed cortical sensory and motor processes and may support crossmodal predictive processing.

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Task complexity temporally extends the causal requirement for visual cortex in perception

The transformation of sensory inputs into behavioral outputs is characterized by an interplay between feedforward and feedback operations in cortical hierarchies. Even in simple sensorimotor transformations, recurrent processing is often expressed in primary cortices in a late phase of the cortical response to sensory stimuli. This late phase is engaged by attention and stimulus complexity, and also encodes sensory-independent factors, including movement and report-related variables. However, despite its pervasiveness, the nature and function of late activity in perceptual decision-making remain unclear. We tested whether the function of late activity depends on the complexity of a sensory change-detection task. Complexity was based on increasing processing requirements for the same sensory stimuli. We found that the temporal window in which V1 is necessary for perceptual decision-making was extended when we increased task complexity, independently of the presented visual stimulus. This window overlapped with the emergence of report-related activity and decreased noise correlations in V1. The onset of these co-occurring activity patterns was time-locked to and preceded reaction time, and predicted the reduction in behavioral performance obtained by optogenetically silencing late V1 activity (>200 ms after stimulus onset), a result confirmed by a second multisensory task with different requirements. Thus, although early visual response components encode all sensory information necessary to solve the task, V1 is not simply relaying information to higher-order areas transforming it into behavioral responses. Rather, task complexity determines the temporal extension of a loop of recurrent activity, which overlaps with report-related activity and determines how perceptual decisions are built.

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Higher-order visual areas broaden stimulus responsiveness in mouse primary visual cortex

Over 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.

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A Deep Predictive Coding Network for Learning Latent Representations

It has been argued that the brain is a prediction machine that continuously learns how to make better predictions about the stimuli received from the external environment. It builds a model of the world around us and uses this model to infer the external stimulus. Predictive coding has been proposed as a mechanism through which the brain might be able to build such a model of the external environment. However, it is not clear how predictive coding can be used to build deep neural network models of the brain while complying with the architectural constraints imposed by the brain. In this paper, we describe an algorithm to build a deep generative model using predictive coding that can be used to infer latent representations about the stimuli received from external environment. Specifically, we used predictive coding to train a deep neural network on real-world images in a unsupervised learning paradigm. To understand the capacity of the network with regards to modeling the external environment, we studied the latent representations generated by the model on images of objects that are never presented to the model during training. Despite the novel features of these objects the model is able to infer the latent representations for them. Furthermore, the reconstructions of the original images obtained from these latent representations preserve the important details of these objects.

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Functional determinants of enhanced and depressed inter-areal information flow in NREM sleep between neuronal ensembles in rat cortex and hippocampus

Compared to wakefulness, neuronal activity during non-REM sleep is characterized by a decreased ability to integrate information, but also by the re-emergence of task-related information patterns. To investigate the mechanisms underlying these seemingly opposing phenomena, we measured directed information flow by computing transfer entropy between neuronal spiking activity in three cortical regions and the hippocampus of rats across brain states. State-dependent information flow resulted to be jointly determined by the anatomical distance between neurons and by their functional specialization. We distinguished two regimes, operating at short and long time scales, respectively. From wakefulness to non-REM sleep, transfer entropy at short time scales increased for inter-areal connections between neurons showing behavioral task correlates. Conversely, transfer entropy at long time scales became stronger between non-task modulated neurons and weaker between task- modulated neurons. These results may explain how, during non-REM sleep, a global inter-areal disconnection is compatible with highly specific task-related information transfer.\n\nAuthor SummaryThe brain remains active during deep sleep, yet we still do not know which rules govern information processing between neurons across wakefulness and sleep. Here we provide a first study of how information flow at the level of spiking activity varies as a function of brain state, temporal scale, brain area and behavioral task correlates of single neurons. We found that inter-areal communication at millisecond time scales is enhanced during sleep compared to wakefulness between neurons that code for task information. Conversely, non-modulated neurons showed more prominent communication at longer time scales. These results indicate that multiple, functionally determined communicative architectures coexist in the brain, and provide a novel framework to understand information processing and its consequences during sleep.

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