Invariance of Mitochondria and Synapses in the Primary Visual Cortex of Mammals Provides Insight Into Energetics and Function.

The cerebral cortex accounts for substantial energy expenditure, primarily driven by the metabolic demands of synaptic signaling. Mitochondria, the organelles responsible for generating cellular energy, play a crucial role in this process. We investigated ultrastructural characteristics of the primary visual cortex in 18 phylogenetically diverse mammals, spanning a broad range of brain sizes from mouse to elephant. Our findings reveal remarkable uniformity in synapse density, postsynaptic density (PSD) length, and mitochondria density, indicating functional and metabolic constraints that maintain these fundamental features. Notably, we observed an average of 1.9 mitochondria per synapse across mammalian species. When considered together with the trend of decreasing neuron density with larger brain size, we find that brain enlargement in mammals is characterized by increasing proportions of synapses and mitochondria per cortical neuron. These results shed light on the adaptive mechanisms and metabolic dynamics that govern cortical ultrastructure across mammals.

Laminar specificity and coverage of viral-mediated gene expression restricted to GABAergic interneurons and their parvalbumin subclass in marmoset primary visual cortex.

In the mammalian neocortex, inhibition is important for dynamically balancing excitation and shaping the response properties of cells and circuits. The various computational functions of inhibition are thought to be mediated by different inhibitory neuron types, of which a large diversity exists in several species. Current understanding of the function and connectivity of distinct inhibitory neuron types has mainly derived from studies in transgenic mice. However, it is unknown whether knowledge gained from mouse studies applies to the non-human primate, the model system closest to humans. The lack of viral tools to selectively access inhibitory neuron types has been a major impediment to studying their function in the primate. Here, we have thoroughly validated and characterized several recently developed viral vectors designed to restrict transgene expression to GABAergic cells or their parvalbumin (PV) subtype, and identified two types that show high specificity and efficiency in marmoset V1. We show that in marmoset V1, AAV-h56D induces transgene expression in GABAergic cells with up to 91-94% specificity and 79% efficiency, but this depends on viral serotype and cortical layer. AAV-PHP.eB-S5E2 induces transgene expression in PV cells across all cortical layers with up to 98% specificity and 86-90% efficiency, depending on layer. Thus, these viral vectors are promising tools for studying GABA and PV cell function and connectivity in the primate cortex.

Neural correlates of dynamic lightness induction.

The lightness of a surface depends not only on the amount of light reflected off, it but also on the context in which it is embedded. Despite a long history of research, neural correlates of context-dependent lightness perception remain a topic of ongoing debate. Here, we seek to expand on the existing literature by measuring functional magnetic resonance imaging (fMRI) responses to lightness variations induced by the context. During the fMRI experiment, we presented 10 participants with a dynamic stimulus in which either the luminance of a disk or its surround is modulated at four different frequencies ranging from 1 to 8 Hz. Behaviorally, when the surround luminance is modulated at low frequencies, participants perceive an illusory change in the lightness of the disk (lightness induction). In contrast, they perceive little or no induction at higher frequencies. Using this frequency dependence and controlling for long-range responses to border contrast and luminance changes, we found that activity in the primary visual cortex (V1) correlates with lightness induction, providing further evidence for the involvement of V1 in the processing of context-dependent lightness.

Asymmetric distribution of color-opponent response types across mouse visual cortex supports superior color vision in the sky.

Color is an important visual feature that informs behavior, and the retinal basis for color vision has been studied across various vertebrate species. While many studies have investigated how color information is processed in visual brain areas of primate species, we have limited understanding of how it is organized beyond the retina in other species, including most dichromatic mammals. In this study, we systematically characterized how color is represented in the primary visual cortex (V1) of mice. Using large-scale neuronal recordings and a luminance and color noise stimulus, we found that more than a third of neurons in mouse V1 are color-opponent in their receptive field center, while the receptive field surround predominantly captures luminance contrast. Furthermore, we found that color-opponency is especially pronounced in posterior V1 that encodes the sky, matching the statistics of natural scenes experienced by mice. Using unsupervised clustering, we demonstrate that the asymmetry in color representations across cortex can be explained by an uneven distribution of green-On/UV-Off color-opponent response types that are represented in the upper visual field. Finally, a simple model with natural scene-inspired parametric stimuli shows that green-On/UV-Off color-opponent response types may enhance the detection of 'predatory'-like dark UV-objects in noisy daylight scenes. The results from this study highlight the relevance of color processing in the mouse visual system and contribute to our understanding of how color information is organized in the visual hierarchy across species.

Heterogeneous orientation tuning in the primary visual cortex of mice diverges from Gabor-like receptive fields in primates.

A key feature of neurons in the primary visual cortex (V1) of primates is their orientation selectivity. Recent studies using deep neural network models showed that the most exciting input (MEI) for mouse V1 neurons exhibit complex spatial structures that predict non-uniform orientation selectivity across the receptive field (RF), in contrast to the classical Gabor filter model. Using local patches of drifting gratings, we identified heterogeneous orientation tuning in mouse V1 that varied up to 90° across sub-regions of the RF. This heterogeneity correlated with deviations from optimal Gabor filters and was consistent across cortical layers and recording modalities (calcium vs. spikes). In contrast, model-synthesized MEIs for macaque V1 neurons were predominantly Gabor like, consistent with previous studies. These findings suggest that complex spatial feature selectivity emerges earlier in the visual pathway in mice than in primates. This may provide a faster, though less general, method of extracting task-relevant information.

A comprehensive data-driven model of cat primary visual cortex.

Knowledge integration based on the relationship between structure and function of the neural substrate is one of the main targets of neuroinformatics and data-driven computational modeling. However, the multiplicity of data sources, the diversity of benchmarks, the mixing of observables of different natures, and the necessity of a long-term, systematic approach make such a task challenging. Here we present a first snapshot of a long-term integrative modeling program designed to address this issue in the domain of the visual system: a comprehensive spiking model of cat primary visual cortex. The presented model satisfies an extensive range of anatomical, statistical and functional constraints under a wide range of visual input statistics. In the presence of physiological levels of tonic stochastic bombardment by spontaneous thalamic activity, the modeled cortical reverberations self-generate a sparse asynchronous ongoing activity that quantitatively matches a range of experimentally measured statistics. When integrating feed-forward drive elicited by a high diversity of visual contexts, the simulated network produces a realistic, quantitatively accurate interplay between visually evoked excitatory and inhibitory conductances; contrast-invariant orientation-tuning width; center surround interactions; and stimulus-dependent changes in the precision of the neural code. This integrative model offers insights into how the studied properties interact, contributing to a better understanding of visual cortical dynamics. It provides a basis for future development towards a comprehensive model of low-level perception.

Sub-bundle based analysis reveals the role of human optic radiation in visual working memory.

White matter (WM) functional activity has been reliably detected through functional magnetic resonance imaging (fMRI). Previous studies have primarily examined WM bundles as unified entities, thereby obscuring the functional heterogeneity inherent within these bundles. Here, for the first time, we investigate the function of sub-bundles of a prototypical visual WM tract-the optic radiation (OR). We use the 7T retinotopy dataset from the Human Connectome Project (HCP) to reconstruct OR and further subdivide the OR into sub-bundles based on the fiber's termination in the primary visual cortex (V1). The population receptive field (pRF) model is then applied to evaluate the retinotopic properties of these sub-bundles, and the consistency of the pRF properties of sub-bundles with those of V1 subfields is evaluated. Furthermore, we utilize the HCP working memory dataset to evaluate the activations of the foveal and peripheral OR sub-bundles, along with LGN and V1 subfields, during 0-back and 2-back tasks. We then evaluate differences in 2bk-0bk contrast between foveal and peripheral sub-bundles (or subfields), and further examine potential relationships between 2bk-0bk contrast and 2-back task d-prime. The results show that the pRF properties of OR sub-bundles exhibit standard retinotopic properties and are typically similar to the properties of V1 subfields. Notably, activations during the 2-back task consistently surpass those under the 0-back task across foveal and peripheral OR sub-bundles, as well as LGN and V1 subfields. The foveal V1 displays significantly higher 2bk-0bk contrast than peripheral V1. The 2-back task d-prime shows strong correlations with 2bk-0bk contrast for foveal and peripheral OR fibers. These findings demonstrate that the blood oxygen level-dependent (BOLD) signals of OR sub-bundles encode high-fidelity visual information, underscoring the feasibility of assessing WM functional activity at the sub-bundle level. Additionally, the study highlights the role of OR in the top-down processes of visual working memory beyond the bottom-up processes for visual information transmission. Conclusively, this study innovatively proposes a novel paradigm for analyzing WM fiber tracts at the individual sub-bundle level and expands understanding of OR function.

State-dependent complexity of the local field potential in the primary visual cortex.

The local field potential (LFP) is as a measure of the combined activity of neurons within a region of brain tissue. While biophysical modeling schemes for LFP in cortical circuits are well established, there is a paramount lack of understanding regarding the LFP properties along the states assumed in cortical circuits over long periods. Here we use a symbolic information approach to determine the statistical complexity based on Jensen disequilibrium measure and Shannon entropy of LFP data recorded from the primary visual cortex (V1) of urethane-anesthetized rats and freely moving mice. Using these information quantifiers, we find consistent relations between LFP recordings and measures of cortical states at the neuronal level. More specifically, we show that LFP's statistical complexity is sensitive to cortical state (characterized by spiking variability), as well as to cortical layer. In addition, we apply these quantifiers to characterize behavioral states of freely moving mice, where we find indirect relations between such states and spiking variability.

Correlated variability and its attentional modulation depend on anatomical connectivity.

Visual cortical neurons show variability in their responses to repeated presentations of a stimulus and a portion of this variability is shared across neurons. Attention may enhance visual perception by reducing shared spiking variability. However, shared variability and its attentional modulation are not consistent within or across cortical areas, and depend on additional factors such as neuronal type. A critical factor that has not been tested is actual anatomical connectivity. We measured spike count correlations among pairs of simultaneously recorded neurons in the primary visual cortex (V1) for which anatomical connectivity was inferred from spiking cross-correlations. Neurons were recorded in monkeys performing a contrast-change discrimination task requiring covert shifts in visual spatial attention. Accordingly, spike count correlations were compared across trials in which attention was directed toward or away from the visual stimulus overlapping recorded neuronal receptive fields. Consistent with prior findings, attention did not significantly alter spike count correlations among random pairings of unconnected V1 neurons. However, V1 neurons connected via excitatory synapses showed a significant reduction in spike count correlations with attention. Interestingly, V1 neurons connected via inhibitory synapses demonstrated high spike count correlations overall that were not modulated by attention. Correlated variability in excitatory circuits also depended upon neuronal tuning for contrast, the task-relevant stimulus feature. These results indicate that shared variability depends on the type of connectivity in neuronal circuits. Also, attention significantly reduces shared variability in excitatory circuits, even when attention effects on randomly sampled neurons within the same area are weak.

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 events1-10. 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. Here we describe a thalamocortical disinhibitory circuit that is required for generating sensory prediction-error signals in mouse primary visual cortex (V1). We show that violating animals' predictions by an unexpected visual stimulus preferentially boosts responses of the layer 2/3 V1 neurons that are most selective for that stimulus. Prediction errors specifically amplify the unexpected visual input, rather than representing non-specific surprise or difference signals about how the visual input deviates from the animal's predictions. This selective amplification is implemented by a cooperative mechanism requiring thalamic input from the pulvinar and cortical vasoactive-intestinal-peptide-expressing (VIP) inhibitory interneurons. In response to prediction errors, VIP neurons inhibit a specific subpopulation of somatostatin-expressing inhibitory interneurons that gate excitatory pulvinar input to V1, resulting in specific pulvinar-driven response amplification of the most stimulus-selective neurons in V1. Therefore, the brain prioritizes unpredicted sensory information by selectively increasing the salience of unpredicted sensory features through the synergistic interaction of thalamic input and neocortical disinhibitory circuits.

Early postnatal development of the primary visual areas 17 and 18 of the cat cerebral cortex: An SMI-32 study.

Using anti-neurofilament H non-phosphorylated antibodies (SMI-32) as markers for the neuronal maturation level and Y channel responsible for motion processing, we investigated early postnatal development of the primary visual areas 17 and 18 in cats aged 0, 10, 14, and 34 days and in adults. Two analyzed parameters of SMI-32-immunolabeling were used: the total proportion of SMI-32-labeling and the density of labeled neurons. (i) The developmental time course of the total proportion of SMI-32-labeling shows the general increase in the accumulation of heavy-chain neurofilaments. This parameter showed a different time course for cortical layer development; the maximal increment in the total labeling in layer V occurred between the second and fifth postnatal weeks and in layers II-III and VI after the fifth postnatal week. In addition, the delay in accumulation of SMI-32-labeling was shown in layer V of the area 17 periphery representation during the first two postnatal weeks. (ii) The density of SMI-32-labeled neurons decreased in all layers of area 18, but was increased, decreased, or had a transient peak in layers II-III, V, and VI of area 17, respectively. The transient peak is in good correspondence with some transient neurochemical features previously revealed for different classes of cortical and thalamic neurons and reflects the time course of the early development of the thalamocortical circuitry. Some similarities between the time courses for the development of SMI-32-labeling in areas 17/18 and in A- and C-laminae of the LGNd allow us to propose heterochronous postnatal development of two Y sub-channels.

Beyond primary visual cortex: The leading role of lateral occipital complex in early conscious visual processing.

The study of the neural substrates that serve conscious vision is one of the unsolved questions of cognitive neuroscience. So far, consciousness literature has endeavoured to disentangle which brain areas and in what order are involved in giving rise to visual awareness, but the problem of consciousness still remains unsolved. Availing of two different but complementary sources of data (i.e., Fast Optical Imaging and EEG), we sought to unravel the neural dynamics responsible for the emergence of a conscious visual experience. Our results revealed that conscious vision is characterized by a significant increase of activation in extra-striate visual areas, specifically in the Lateral Occipital Complex (LOC), and that, more interestingly, such activity occurred in the temporal window of the ERP component commonly thought to represent the electrophysiological signature of visual awareness, i.e., the Visual Awareness Negativity (VAN). Furthermore, Granger causality analysis, performed to further investigate the flow of activity occurring in the investigated areas, unveiled that neural processes relating to conscious perception mainly originated in LOC and subsequently spread towards visual and motor areas. In general, the results of the present study seem to advocate for an early contribution of LOC in conscious vision, thus suggesting that it could represent a reliable neural correlate of visual awareness. Conversely, striate visual areas, showing awareness-related activity only in later stages of stimulus processing, could be part of the cascade of neural events following awareness emergence.

An essential role for the latero-medial secondary visual cortex in the acquisition and retention of visual perceptual learning in mice.

Perceptual learning refers to any change in discrimination abilities as a result of practice, a fundamental process that improves the organism's response to the external environment. Visual perceptual learning (vPL) is supposed to rely on functional rearrangements in brain circuity occurring at early stages of sensory processing, with a pivotal role for the primary visual cortex (V1). However, top-down inputs from higher-order visual areas (HVAs) have been suggested to play a key part in vPL, conveying information on attention, expectation and the precise nature of the perceptual task. A direct assessment of the possibility to modulate vPL by manipulating top-down activity in awake subjects is still missing. Here, we used a combination of chemogenetics, behavioral analysis and multichannel electrophysiological assessments to show a critical role in vPL acquisition and retention for neuronal activity in the latero-medial secondary visual cortex (LM), the prime source for top-down feedback projections reentering V1.

Dissonant music engages early visual processing.

The neuroscientific examination of music processing in audio-visual contexts offers a valuable framework to assess how auditory information influences the emotional encoding of visual information. Using fMRI during naturalistic film viewing, we investigated the neural mechanisms underlying the effect of music on valence inferences during mental state attribution. Thirty-eight participants watched the same short-film accompanied by systematically controlled consonant or dissonant music. Subjects were instructed to think about the main character's intentions. The results revealed that increasing levels of dissonance led to more negatively valenced inferences, displaying the profound emotional impact of musical dissonance. Crucially, at the neuroscientific level and despite music being the sole manipulation, dissonance evoked the response of the primary visual cortex (V1). Functional/effective connectivity analysis showed a stronger coupling between the auditory ventral stream (AVS) and V1 in response to tonal dissonance and demonstrated the modulation of early visual processing via top-down feedback inputs from the AVS to V1. These V1 signal changes indicate the influence of high-level contextual representations associated with tonal dissonance on early visual cortices, serving to facilitate the emotional interpretation of visual information. Our results highlight the significance of employing systematically controlled music, which can isolate emotional valence from the arousal dimension, to elucidate the brain's sound-to-meaning interface and its distributive crossmodal effects on early visual encoding during naturalistic film viewing.

Development of ocular dominance columns across rodents and other species: revisiting the concept of critical period plasticity.

The existence of cortical columns, regarded as computational units underlying both lower and higher-order information processing, has long been associated with highly evolved brains, and previous studies suggested their absence in rodents. However, recent discoveries have unveiled the presence of ocular dominance columns (ODCs) in the primary visual cortex (V1) of Long-Evans rats. These domains exhibit continuity from layer 2 through layer 6, confirming their identity as genuine ODCs. Notably, ODCs are also observed in Brown Norway rats, a strain closely related to wild rats, suggesting the physiological relevance of ODCs in natural survival contexts, although they are lacking in albino rats. This discovery has enabled researchers to explore the development and plasticity of cortical columns using a multidisciplinary approach, leveraging studies involving hundreds of individuals-an endeavor challenging in carnivore and primate species. Notably, developmental trajectories differ depending on the aspect under examination: while the distribution of geniculo-cortical afferent terminals indicates matured ODCs even before eye-opening, consistent with prevailing theories in carnivore/primate studies, examination of cortical neuron spiking activities reveals immature ODCs until postnatal day 35, suggesting delayed maturation of functional synapses which is dependent on visual experience. This developmental gap might be recognized as 'critical period' for ocular dominance plasticity in previous studies. In this article, I summarize cross-species differences in ODCs and geniculo-cortical network, followed by a discussion on the development, plasticity, and evolutionary significance of rat ODCs. I discuss classical and recent studies on critical period plasticity in the venue where critical period plasticity might be a component of experience-dependent development. Consequently, this series of studies prompts a paradigm shift in our understanding of species conservation of cortical columns and the nature of plasticity during the classical critical period.

Sex-specific alterations in visual properties induced by single prolonged stress model.

Patients with post-traumatic stress disorder (PTSD) exhibit sex differences in symptomology, with women more likely to report higher rates of intrusive and avoidance symptoms than men, underscoring the need for sex-informed approaches to research and treatment. Our study delved into the sex-specific aspects of stress-induced visual impairments using the single prolonged stress (SPS) model, a partially validated rodent model for PTSD. Male SPS mice exhibit heightened optimal spatial frequency (SF) of primary visual cortex (V1) neurons, while female counterparts exhibit decreased optimal temporal frequency (TF) of V1 neurons. This phenomenon persisted until the 29th day after SPS modeling, and it may be the physiological basis for the observed increase in visual acuity in male SPS mice in visual water task. Furthermore, our study found that corticotropin-releasing factor receptor 1 regulated optimal TF and optimal SF of V1 in mice, but did not exhibit sex differences. These findings indicated that severe stress induces sex-specific effects on visual function.

Rapid effects of tryptamine psychedelics on perceptual distortions and early visual cortical population receptive fields.

N, N-dimethyltryptamine (DMT) is a psychedelic tryptamine acting on 5-HT2A serotonin receptors, which is associated with intense visual hallucinatory phenomena and perceptual changes such as distortions in visual space. The neural underpinnings of these effects remain unknown. We hypothesised that changes in population receptive field (pRF) properties in the primary visual cortex (V1) might underlie visual perceptual experience. We tested this hypothesis using magnetic resonance imaging (MRI) in a within-subject design. We used a technique called pRF mapping, which measures neural population visual response properties and retinotopic maps in early visual areas. We show that in the presence of visual effects, as documented by the Hallucinogen Rating Scale (HRS), the mean pRF sizes in V1 significantly increase in the peripheral visual field for active condition (inhaled DMT) compared to the control. Eye and head movement differences were absent across conditions. This evidence for short-term effects of DMT in pRF may explain perceptual distortions induced by psychedelics such as field blurring, tunnel vision (peripheral vision becoming blurred while central vision remains sharp) and the enlargement of nearby visual space, particularly at the visual locations surrounding the fovea. Our findings are also consistent with a mechanistic framework whereby gain control of ongoing and evoked activity in the visual cortex is controlled by activation of 5-HT2A receptors.

Flexible neural population dynamics govern the speed and stability of sensory encoding in mouse visual cortex.

Time courses of neural responses underlie real-time sensory processing and perception. How these temporal dynamics change may be fundamental to how sensory systems adapt to different perceptual demands. By simultaneously recording from hundreds of neurons in mouse primary visual cortex, we examined neural population responses to visual stimuli at sub-second timescales, during different behavioural states. We discovered that during active behavioural states characterised by locomotion, single-neurons shift from transient to sustained response modes, facilitating rapid emergence of visual stimulus tuning. Differences in single-neuron response dynamics were associated with changes in temporal dynamics of neural correlations, including faster stabilisation of stimulus-evoked changes in the structure of correlations during locomotion. Using Factor Analysis, we examined temporal dynamics of latent population responses and discovered that trajectories of population activity make more direct transitions between baseline and stimulus-encoding neural states during locomotion. This could be partly explained by dampening of oscillatory dynamics present during stationary behavioural states. Functionally, changes in temporal response dynamics collectively enabled faster, more stable and more efficient encoding of new visual information during locomotion. These findings reveal a principle of how sensory systems adapt to perceptual demands, where flexible neural population dynamics govern the speed and stability of sensory encoding.

Running into differences.

Body movement does not significantly increase neuronal activity in the primary visual cortex of marmosets, in contrast to the effects observed in mice.

Longitudinal stability of individual brain plasticity patterns in blindness.

The primary visual cortex (V1) in blindness is engaged in a wide spectrum of tasks and sensory modalities, including audition, touch, language, and memory. This widespread involvement raises questions regarding the constancy of its role and whether it might exhibit flexibility in its function over time, connecting to diverse network functions specific to task demands. This would suggest that reorganized V1 assumes a role like multiple-demand system regions. Alternatively, varying patterns of plasticity in blind V1 may be attributed to individual factors, with different blind individuals recruiting V1 preferentially for different functions. In support of this, we recently showed that V1 functional connectivity (FC) varies greatly across blind individuals. But do these represent stable individual patterns of plasticity, or are they driven more by instantaneous changes, like a multiple-demand system now inhabiting V1? Here, we tested whether individual FC patterns from the V1 of blind individuals are stable over time. We show that over two years, FC from the V1 is unique and highly stable in a small sample of repeatedly sampled congenitally blind individuals. Further, using multivoxel pattern analysis, we demonstrate that the unique reorganization patterns of these individuals allow decoding of participant identity. Together with recent evidence for substantial individual differences in V1 connectivity, this indicates that there may be a consistent role for V1 in blindness, which may differ for each individual. Further, it suggests that the variability in visual reorganization in blindness across individuals could be used to seek stable neuromarkers for sight rehabilitation and assistive approaches.