Parallel Streams of Direct Corticogeniculate Feedback from Mid-level Extrastriate Cortex in the Macaque Monkey.

First-order thalamic nuclei receive feedforward signals from peripheral receptors and relay these signals to primary sensory cortex. Primary sensory cortex, in turn, provides reciprocal feedback to first-order thalamus. Because the vast majority of sensory thalamocortical inputs target primary sensory cortex, their complementary corticothalamic neurons are assumed to be similarly restricted to primary sensory cortex. We upend this assumption by characterizing morphologically diverse neurons in multiple mid-level visual cortical areas of the primate (Macaca mulatta) brain that provide direct feedback to the primary visual thalamus, the dorsal lateral geniculate nucleus (LGN). Although the majority of geniculocortical neurons project to primary visual cortex (V1), a minority, located mainly in the koniocellular LGN layers, provide direct input to extrastriate visual cortex. These "V1-bypassing" projections may be implicated in blindsight. We hypothesized that geniculocortical inputs directly targeting extrastriate cortex should be complemented by reciprocal corticogeniculate circuits. Using virus-mediated circuit tracing, we discovered corticogeniculate neurons throughout three mid-level extrastriate areas: MT, MST, and V4. Quantitative morphological analyses revealed nonuniform distributions of unique cell types across areas. Many extrastriate corticogeniculate neurons had spiny stellate morphology, suggesting possible targeting of koniocellular LGN layers. Importantly though, multiple morphological types were observed across areas. Such morphological diversity could suggest parallel streams of V1-bypassing corticogeniculate feedback at multiple stages of the visual processing hierarchy. Furthermore, the presence of corticogeniculate neurons across visual cortex necessitates a reevaluation of the LGN as a hub for visual information rather than a simple relay.

Working memory signals in early visual cortex are present in weak and strong imagers.

It has been suggested that visual images are memorized across brief periods of time by vividly imagining them as if they were still there. In line with this, the contents of both working memory and visual imagery are known to be encoded already in early visual cortex. If these signals in early visual areas were indeed to reflect a combined imagery and memory code, one would predict them to be weaker for individuals with reduced visual imagery vividness. Here, we systematically investigated this question in two groups of participants. Strong and weak imagers were asked to remember images across brief delay periods. We were able to reliably reconstruct the memorized stimuli from early visual cortex during the delay. Importantly, in contrast to the prediction, the quality of reconstruction was equally accurate for both strong and weak imagers. The decodable information also closely reflected behavioral precision in both groups, suggesting it could contribute to behavioral performance, even in the extreme case of completely aphantasic individuals. Our data thus suggest that working memory signals in early visual cortex can be present even in the (near) absence of phenomenal imagery.

Transcranial Low-Intensity Focused Ultrasound Stimulation of the Visual Thalamus Produces Long-Term Depression of Thalamocortical Synapses in the Adult Visual Cortex.

Transcranial focused ultrasound stimulation (tFUS) is a noninvasive neuromodulation technique, which can penetrate deeper and modulate neural activity with a greater spatial resolution (on the order of millimeters) than currently available noninvasive brain stimulation methods, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). While there are several studies demonstrating the ability of tFUS to modulate neuronal activity, it is unclear whether it can be used for producing long-term plasticity as needed to modify circuit function, especially in adult brain circuits with limited plasticity such as the thalamocortical synapses. Here we demonstrate that transcranial low-intensity focused ultrasound (LIFU) stimulation of the visual thalamus (dorsal lateral geniculate nucleus, dLGN), a deep brain structure, leads to NMDA receptor (NMDAR)-dependent long-term depression of its synaptic transmission onto layer 4 neurons in the primary visual cortex (V1) of adult mice of both sexes. This change is not accompanied by large increases in neuronal activity, as visualized using the cFos Targeted Recombination in Active Populations (cFosTRAP2) mouse line, or activation of microglia, which was assessed with IBA-1 staining. Using a model (SONIC) based on the neuronal intramembrane cavitation excitation (NICE) theory of ultrasound neuromodulation, we find that the predicted activity pattern of dLGN neurons upon sonication is state-dependent with a range of activity that falls within the parameter space conducive for inducing long-term synaptic depression. Our results suggest that noninvasive transcranial LIFU stimulation has a potential for recovering long-term plasticity of thalamocortical synapses in the postcritical period adult brain.

Cortical depth profiles in primary visual cortex for illusory and imaginary experiences.

Visual illusions and mental imagery are non-physical sensory experiences that involve cortical feedback processing in the primary visual cortex. Using laminar functional magnetic resonance imaging (fMRI) in two studies, we investigate if information about these internal experiences is visible in the activation patterns of different layers of primary visual cortex (V1). We find that imagery content is decodable mainly from deep layers of V1, whereas seemingly 'real' illusory content is decodable mainly from superficial layers. Furthermore, illusory content shares information with perceptual content, whilst imagery content does not generalise to illusory or perceptual information. Together, our results suggest that illusions and imagery, which differ immensely in their subjective experiences, also involve partially distinct early visual microcircuits. However, overlapping microcircuit recruitment might emerge based on the nuanced nature of subjective conscious experience.

Causal oscillations in the visual thalamo-cortical network in sustained attention in ferrets.

Sustained visual attention allows us to process and react to unpredictable, behaviorally relevant sensory input. Sustained attention engages communication between the higher-order visual thalamus and its connected cortical regions. However, it remains unclear whether there is a causal relationship between oscillatory circuit dynamics and attentional behavior in these thalamo-cortical circuits. By using rhythmic optogenetic stimulation in the ferret, we provide causal evidence that higher-order visual thalamus coordinates thalamo-cortical and cortico-cortical functional connectivity during sustained attention via spike-field phase locking. Increasing theta but not alpha power in the thalamus improved accuracy and reduced omission rates in a sustained attention task. Further, the enhancement of effective connectivity by stimulation was correlated with improved behavioral performance. Our work demonstrates a potential circuit-level causal mechanism for how the higher-order visual thalamus modulates cortical communication through rhythmic synchronization during sustained attention.

Sound suppresses earliest visual cortical processing after sight recovery in congenitally blind humans.

Neuroscientific research has consistently shown more extensive non-visual activity in the visual cortex of congenitally blind humans compared to sighted controls; a phenomenon known as crossmodal plasticity. Whether or not crossmodal activation of the visual cortex retracts if sight can be restored is still unknown. The present study, involving a rare group of sight-recovery individuals who were born pattern vision blind, employed visual event-related potentials to investigate persisting crossmodal modulation of the initial visual cortical processing stages. Here we report that the earliest, stimulus-driven retinotopic visual cortical activity (<100 ms) was suppressed in a spatially specific manner in sight-recovery individuals when concomitant sounds accompanied visual stimulation. In contrast, sounds did not modulate the earliest visual cortical response in two groups of typically sighted controls, nor in a third control group of sight-recovery individuals who had suffered a transient phase of later (rather than congenital) visual impairment. These results provide strong evidence for persisting crossmodal activity in the visual cortex after sight recovery following a period of congenital visual deprivation. Based on the time course of this modulation, we speculate on a role of exuberant crossmodal thalamic input which may arise during a sensitive phase of brain development.

The possible protective role of selenium on the visual cortex of adult albino rat on exposure to potassium dichromate.

The visual cortex is very important in mammals for processing of visual information. Exposure to heavy metals such as potassium dichromate poses serious health threat to human beings. The aim of this work is to study the effect of potassium dichromate on the visual cortex of adult albino rat and also to identify the possibility of selenium as protective agent against toxicity of potassium dichromate. A total number of 40 adult albino rats weighting (200-250) gm were used. They divided into four groups: control group, potassium dichromate received group, potassium dichromate and selenium received group and selenium received group. The rats received treatment for 6 weeks. After 6 weeks, they were sacrificed. The present study showed that potassium dichromate causes degeneration of granular neurons in layer IV and pyramidal neurons in layer V. Morphometric results revealed statistically significant decrease in the number of granule and pyramidal cells in potassium dichromate received group as compared with control group. Most of degenerative changes are improved by selenium.

الدور الوقائي المحتمل للسيلينيوم على القشرة المخية البصرية للفأر الابيض البالغ عند التعرضللدايكرومات البوتاسيومسالي سيد أنور-هالة محمد حسانينقسم التشريح الادمي وعلم الاجنة -كلية الطب البشرى- جامعة اسيوطالقشرة البصرية مهمة جدا في الثدييات لمعالجة المعلومات المرئية. يشكل التعرض للمعادنالثقيلة مثل ثنائي كرومات البوتاسيوم تهديداً صحياً خطيراً للإنسان. الهدف من هذا العمل هودراسة تأثير ثنائي كرومات البوتاسيوم على القشرة البصرية لجرذ ألبينو البالغ وكذلك التعرفعلى إمكانية استخدام السيلينيوم كعامل وقائي ضد سمية ثنائي كرومات البوتاسيوم. تم استخدامجرذ من الجرذان البالغة وزنها (200-250) جرام. تم تقسيمهم إلى 4 مجموعات: المجموعة40الضابطة ، المجموعة المستلمة ثنائي كرومات البوتاسيوم ، المجموعة المستلمة ثاني كروماتالبوتاسيوم والسيلينيوم المجموعة المستلمة سيلينيوم تلقتالفئران العلاج لمدة 6أسابيع. بعد ستة أسابيع تم التضحية بهم. أظهرت الدراسة الحالية أن ثنائي كرومات البوتاسيوميسبب تنكس الخلايا العصبية الحبيبية في الطبقة الرابعة والخلايا العصبية الهرمية في الطبقةالخامسة. أظهرت نتائج القياس المورفومتري انخفاضًا ذا دلالة إحصائية في عدد الخلايا الحبيبيةوالهرمية في المجموعة التي تم تلقيها من ثنائي كرومات البوتاسيوم مقارنة بمجموعة التحكم. يتمتحسين معظم التغييرات التنكسية بواسطة السيلينيوم.[Figure: see text].

Multi-layered maps of neuropil with segmentation-guided contrastive learning.

Maps of the nervous system that identify individual cells along with their type, subcellular components and connectivity have the potential to elucidate fundamental organizational principles of neural circuits. Nanometer-resolution imaging of brain tissue provides the necessary raw data, but inferring cellular and subcellular annotation layers is challenging. We present segmentation-guided contrastive learning of representations (SegCLR), a self-supervised machine learning technique that produces representations of cells directly from 3D imagery and segmentations. When applied to volumes of human and mouse cortex, SegCLR enables accurate classification of cellular subcompartments and achieves performance equivalent to a supervised approach while requiring 400-fold fewer labeled examples. SegCLR also enables inference of cell types from fragments as small as 10 µm, which enhances the utility of volumes in which many neurites are truncated at boundaries. Finally, SegCLR enables exploration of layer 5 pyramidal cell subtypes and automated large-scale analysis of synaptic partners in mouse visual cortex.

Thalamic regulation of ocular dominance plasticity in adult visual cortex.

Experience-dependent plasticity in the adult visual system is generally thought of as a cortical process. However, several recent studies have shown that perceptual learning or monocular deprivation can also induce plasticity in the adult dorsolateral geniculate nucleus (dLGN) of the thalamus. How plasticity in the thalamus and cortex interact in the adult visual system is ill-understood. To assess the influence of thalamic plasticity on plasticity in primary visual cortex (V1), we made use of our previous finding that during the critical period ocular dominance (OD) plasticity occurs in dLGN and requires thalamic synaptic inhibition. Using multielectrode recordings we find that this is also true in adult mice, and that in the absence of thalamic inhibition and plasticity, OD plasticity in adult V1 is absent. To study the influence of V1 on thalamic plasticity, we silenced V1 and show that during the critical period, but not in adulthood, the OD shift in dLGN is partially caused by feedback from V1. We conclude that during adulthood the thalamus plays an unexpectedly dominant role in experience-dependent plasticity in V1. Our findings highlight the importance of considering the thalamus as a potential source of plasticity in learning events that are typically thought of as cortical processes.

Spatiotemporal dynamics of self-generated imagery reveal a reverse cortical hierarchy from cue-induced imagery.

Visual imagery allows for the construction of rich internal experience in our mental world. However, it has remained poorly understood how imagery experience derives volitionally as opposed to being cue driven. Here, using electroencephalography and functional magnetic resonance imaging, we systematically investigate the spatiotemporal dynamics of self-generated imagery by having participants volitionally imagining one of the orientations from a learned pool. We contrast self-generated imagery with cue-induced imagery, where participants imagined line orientations based on associative cues acquired previously. Our results reveal overlapping neural signatures of cue-induced and self-generated imagery. Yet, these neural signatures display substantially differential sensitivities to the two types of imagery: self-generated imagery is supported by an enhanced involvement of the anterior cortex in representing imagery contents. By contrast, cue-induced imagery is supported by enhanced imagery representations in the posterior visual cortex. These results jointly support a reverse cortical hierarchy in generating and maintaining imagery contents in self-generated versus externally cued imagery.

A laminar model for the joint development of ocular dominance columns and CO blobs in the primary visual cortex.

In this paper, we present a multi-layer, activity-dependent model for the joint development of ocular dominance (OD) columns and cytochrome oxidase (CO) blobs in primate V1. For simplicity, we focus on layers 4C and 2/3 with both layers receiving direct thalamic inputs and layer 4C sending vertical projections to layer 2/3. Both the thalamic and the vertical connections are taken to be modifiable by activity. Using a correlation-based Hebbian learning rule with subtractive normalization, we show how the formation of an OD map in layer 4C is inherited by layer 2/3 via the vertical projections. Competition between these feedforward projections and the direct thalamic input to layer 2/3 then results in the formation of CO blobs superimposed upon the ocular dominance map. The spacing of the OD columns is determined by the spatial profile of the intralaminar connections within layer 4, while the spacing of CO blobs depends both on the width of the OD columns inherited from layer 4 and the spatial distribution of intralaminar connections within the superficial layer. The resulting CO blob distribution is shown to be consistent with experimental data. In addition, we numerically simulate monocular deprivation and find that while the CO blob distribution is unaltered, the OD pattern undergoes modification. The OD stripes of the deprived eye narrow, whereas the OD stripes for the remaining open eye widen.

Spatiotemporal dynamics across visual cortical laminae support a predictive coding framework for interpreting mismatch responses.

Context modulates neocortical processing of sensory data. Unexpected visual stimuli elicit large responses in primary visual cortex (V1)-a phenomenon known as deviance detection (DD) at the neural level, or "mismatch negativity" (MMN) when measured with EEG. It remains unclear how visual DD/MMN signals emerge across cortical layers, in temporal relation to the onset of deviant stimuli, and with respect to brain oscillations. Here we employed a visual "oddball" sequence-a classic paradigm for studying aberrant DD/MMN in neuropsychiatric populations-and recorded local field potentials in V1 of awake mice with 16-channel multielectrode arrays. Multiunit activity and current source density profiles showed that although basic adaptation to redundant stimuli was present early (50 ms) in layer 4 responses, DD emerged later (150-230 ms) in supragranular layers (L2/3). This DD signal coincided with increased delta/theta (2-7 Hz) and high-gamma (70-80 Hz) oscillations in L2/3 and decreased beta oscillations (26-36 Hz) in L1. These results clarify the neocortical dynamics elicited during an oddball paradigm at a microcircuit level. They are consistent with a predictive coding framework, which posits that predictive suppression is present in cortical feed-back circuits, which synapse in L1, whereas "prediction errors" engage cortical feed-forward processing streams, which emanate from L2/3.

Thalamocortical circuits for the formation of hierarchical pathways in the mammalian visual cortex.

External sensory inputs propagate from lower-order to higher-order brain areas, and the hierarchical neural network supporting this information flow is a fundamental structure of the mammalian brain. In the visual system, multiple hierarchical pathways process different features of the visual information in parallel. The brain can form this hierarchical structure during development with few individual differences. A complete understanding of this formation mechanism is one of the major goals of neuroscience. For this purpose, it is necessary to clarify the anatomical formation process of connections between individual brain regions and to elucidate the molecular and activity-dependent mechanisms that instruct these connections in each areal pair. Over the years, researchers have unveiled developmental mechanisms of the lower-order pathway from the retina to the primary visual cortex. The anatomical formation of the entire visual network from the retina to the higher visual cortex has recently been clarified, and higher-order thalamic nuclei are gaining attention as key players in this process. In this review, we summarize the network formation process in the mouse visual system, focusing on projections from the thalamic nuclei to the primary and higher visual cortices, which are formed during the early stages of development. Then, we discuss how spontaneous retinal activity that propagates through thalamocortical pathways is essential for the formation of corticocortical connections. Finally, we discuss the possible role of higher-order thalamocortical projections as template structures in the functional maturation of visual pathways that process different visual features in parallel.

Bartolomeo Panizza (1785-1867) and his contribution to the discovery of the visual cortex.

Bartolomeo Panizza (1785-1867) was an eminent anatomist and a pupil of Antonio Scarpa (1752-1832) at the University of Pavia. In 1855, before the revolutionary studies of Paul Broca (1824-1880) on aphasia that supported the theory of cortical localizations, Panizza delivered a lecture in Milan on the anatomy of the visual system, Osservazioni sul Nervo Ottico ("Observations on the optic nerve"). This lecture contains the first description of the cortical projection of the visual pathways in the occipital lobe, anticipating the revolutionary studies performed by Hermann Munk (1839-1912) in the late 19th century. The findings of Panizza questioned the assumption of the French physiologist, Marie-Jean-Pierre Flourens (1794-1867) who was defending the holistic concept of cerebral equipotentiality, which was widely accepted among the scientific community in the early 19th century. The present essay highlights the life and the scientific studies of Bartolomeo Panizza, with emphasis on the issue of cerebral localization that was simmering in the scientific community at that time.

Vividness as the similarity between generated imagery and an internal model.

Vividness in visual mental imagery has been relatively under-explored compared to imagery's representational format and neural mechanisms. In this paper, we take a deeper look at vividness and suggest that in re-framing it, we can potentially reconcile disparate findings regarding visual cortex activation during imagery. Unlike traditional views of vividness that define the concept in terms of perception, we frame vividness in terms of imagery's relation to an internal model; the closer the generated imagery is to this model, the more vivid it is. This view is considered alongside existing neuroscientific, psychological, and philosophical research, as well as directions for future research.

Gabor and Non-Gabor Neural Representations Are Shared between Visual Perception and Mental Imagery.

Visual perception and mental imagery have been shown to share a hierarchical topological visual structure of neural representation, despite the existence of dissociation of neural substrate between them in function and structure. However, we have limited knowledge about how the visual hierarchical cortex is involved in visual perception and visual imagery in a unique and shared fashion. In this study, a data set including a visual perception and an imagery experiment with human participants was used to train 2 types of voxel-wise encoding models. These models were based on Gabor features and voxel activity patterns of high-level visual cortex (i.e., fusiform face area, parahippocampal place area, and lateral occipital complex) to predict activity in the early visual cortex (EVC, i.e., V1, V2, V3) during perception, and then tested with respect to the generalization of these models to mental imagery. Our results showed that during perception and imagery, activities in the EVC could be independently predicted by the Gabor features and activity of high-level visual cortex via voxel-wise encoding models, which suggested that perception and imagery might share neural representation in the EVC. We further found Gabor-specific and non-Gabor-specific patterns of neural response to stimuli in the EVC, which were shared by perception and imagery. These findings provide insight into the mechanisms of how visual perception and imagery share representation in the EVC.

Impact of Acute Visual Experience on Development of LGN Receptive Fields in the Ferret.

Selectivity for direction of motion is a key feature of primary visual cortical neurons. Visual experience is required for direction selectivity in carnivore and primate visual cortex, but the circuit mechanisms of its formation remain incompletely understood. Here, we examined how developing lateral geniculate nucleus (LGN) neurons may contribute to cortical direction selectivity. Using in vivo electrophysiology techniques, we examined LGN receptive field properties of visually naive female ferrets before and after exposure to 6 h of motion stimuli to assess the effect of acute visual experience on LGN cell development. We found that acute experience with motion stimuli did not significantly affect the weak orientation or direction selectivity of LGN neurons. In addition, we found that neither latency nor sustainedness or transience of LGN neurons significantly changed with acute experience. These results suggest that the direction selectivity that emerges in cortex after acute experience is computed in cortex and cannot be explained by changes in LGN cells.SIGNIFICANCE STATEMENT The development of typical neural circuitry requires experience-independent and experience-dependent factors. In the visual cortex of carnivores and primates, selectivity for motion arises as a result of experience, but we do not understand whether the major brain area that sits between the retina and the visual cortex-the lateral geniculate nucleus of the thalamus-also participates. Here, we found that lateral geniculate neurons do not exhibit changes as a result of several hours of visual experience with moving stimuli at a time when visual cortical neurons undergo a rapid change. We conclude that lateral geniculate neurons do not participate in this plasticity and that changes in cortex are likely responsible for the development of direction selectivity in carnivores and primates.

Thalamic regulation of a visual critical period and motor behavior.

During the visual critical period (CP), sensory experience refines the structure and function of visual circuits. The basis of this plasticity was long thought to be limited to cortical circuits, but recently described thalamic plasticity challenges this dogma and demonstrates greater complexity underlying visual plasticity. Yet how visual experience modulates thalamic neurons or how the thalamus modulates CP timing is incompletely understood. Using a larval zebrafish, thalamus-centric ocular dominance model, we show functional changes in the thalamus and a role of inhibitory signaling to establish CP timing using a combination of functional imaging, optogenetics, and pharmacology. Hemisphere-specific changes in genetically defined thalamic neurons correlate with changes in visuomotor behavior, establishing a role of thalamic plasticity in modulating motor performance. Our work demonstrates that visual plasticity is broadly conserved and that visual experience leads to neuron-level functional changes in the thalamus that require inhibitory signaling to establish critical period timing.

Brain State-Dependent Modulation of Thalamic Visual Processing by Cortico-Thalamic Feedback.

The behavioral state of a mammal impacts how the brain responds to visual stimuli as early as in the dorsolateral geniculate nucleus of the thalamus (dLGN), the primary relay of visual information to the cortex. A clear example of this is the markedly stronger response of dLGN neurons to higher temporal frequencies of the visual stimulus in alert as compared with quiescent animals. The dLGN receives strong feedback from the visual cortex, yet whether this feedback contributes to these state-dependent responses to visual stimuli is poorly understood. Here, we show that in male and female mice, silencing cortico-thalamic feedback profoundly reduces state-dependent differences in the response of dLGN neurons to visual stimuli. This holds true for dLGN responses to both temporal and spatial features of the visual stimulus. These results reveal that the state-dependent shift of the response to visual stimuli in an early stage of visual processing depends on cortico-thalamic feedback.SIGNIFICANCE STATEMENT Brain state affects even the earliest stages of sensory processing. A clear example of this phenomenon is the change in thalamic responses to visual stimuli depending on whether the animal's brain is in an alert or quiescent state. Despite the radical impact that brain state has on sensory processing, the underlying circuits are still poorly understood. Here, we show that both the temporal and spatial response properties of thalamic neurons to visual stimuli depend on the state of the animal and, crucially, that this state-dependent shift relies on the feedback projection from visual cortex to thalamus.

Thalamocortical boutons cluster by ON/OFF responses in mouse primary visual cortex.

In higher mammals, the thalamic afferents to primary visual cortex cluster according to their responses to increases (ON) or decreases (OFF) in luminance. This feature of thalamocortical wiring is thought to create columnar, ON/OFF domains in V1. We have recently shown that mice also have ON/OFF cortical domains, but the organization of their thalamic afferents remains unknown. Here we measured the visual responses of thalamocortical boutons with two-photon imaging and found that they also cluster in space according to ON/OFF responses. Moreover, fluctuations in the relative density of ON/OFF boutons mirror fluctuations in the relative density of ON/OFF receptive field positions on the visual field. These findings indicate a segregation of ON/OFF signals already present in the thalamic input. We propose that ON/OFF clustering may reflect the spatial distribution of ON/OFF responses in retinal ganglion cell mosaics.NEW & NOTEWORTHY Neurons in primary visual cortex cluster into ON and OFF domains, which have been shown to be linked to the organization of receptive fields and cortical maps. Here we show that in the mouse such clustering is already present in the geniculate input, suggesting that the cortical architecture may be shaped by the representation of ON/OFF signals in the thalamus and the retina.