Layers Of Primary Visual Cortex Research Articles

Influence of white-light-emitting diodes on primary visual cortex layer 5 pyramidal neurons (V1L5PNs) and remodeling by blue-light-blocking lenses

Studies have explored the consequences of excessive exposure to white-light-emitting diodes (LEDs) in the retina. Hence, we aimed to assess the implications of such exposure on structural alterations of the visual cortex, learning and memory, and amelioration by blue-light-blocking lenses (BBLs). Eight-week-old Wistar rats (n = 24) were used for the experiment and divided into four groups (n = 6 in each group) as control, white LED light exposure (LE), BBL Crizal Prevencia-1 (CP), and DuraVision Blue-2 (DB). Animals in the exposure group were exposed to white LED directly for 28 days (12:12-h light/dark cycle), whereas animals in the BBL groups were exposed to similar light with BBLs attached to the LEDs. Post-exposure, a Morris water maze was performed for memory retention, followed by structural analysis of layer 5 pyramidal neurons in the visual cortex. We observed a significant difference (P < 0.001) in the functional test on day 1 and day 2 of training in the LE group. Structural analysis of Golgi-Cox-stained visual cortex layer 5 pyramidal neurons showed significant alterations in the apical and basal branching points (p < 0.001) and basal intersection points (p < 0.001) in the LE group. Post hoc analysis revealed significant changes between (p < 0.001) LE and CP and (p < 0.001) CP and DB groups. Constant and cumulative exposure to white LEDs presented with structural and functional alterations in the visual cortex, which are partly remodeled by BBLs.

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.

Mnemonic representations in human lateral geniculate nucleus.

There is a growing appreciation for the role of the thalamus in high-level cognition. Motivated by findings that internal cognitive state drives activity in feedback layers of primary visual cortex (V1) that target the lateral geniculate nucleus (LGN), we investigated the role of LGN in working memory (WM). Specifically, we leveraged model-based neuroimaging approaches to test the hypothesis that human LGN encodes information about spatial locations temporarily encoded in WM. First, we localized and derived a detailed topographic organization in LGN that accords well with previous findings in humans and non-human primates. Next, we used models constructed on the spatial preferences of LGN populations in order to reconstruct spatial locations stored in WM as subjects performed modified memory-guided saccade tasks. We found that population LGN activity faithfully encoded the spatial locations held in memory in all subjects. Importantly, our tasks and models allowed us to dissociate the locations of retinal stimulation and the motor metrics of memory-guided saccades from the maintained spatial locations, thus confirming that human LGN represents true WM information. These findings add LGN to the growing list of subcortical regions involved in WM, and suggest a key pathway by which memories may influence incoming processing at the earliest levels of the visual hierarchy.

Study on the mechanism of visual aging in cats’ primary visual cortex based on BDNF-TrkB signal pathway

To explore the expression of brain-derived neurotrophic factor (BDNF) and specific receptor tyrosine kinase receptor B (TrkB) in the primary visual cortex of young and old cats, especially to reveal the age-related differences in the mediating mechanism of BDNF-TrkB signaling pathway in cats’ visual cortex and their possible effects on synaptic plasticity, Nissl staining was used to display neurons in each layer of cats’ primary visual cortex, and immunohistochemical ABC method was used to label BDNF and TrkB immunopositive cells in each layer of cats’ primary visual cortex. The BDNF and TrkB receptor immunoreactive neurons and non-neurons were observed and photographed. Their density and immunoreactive intensity were measured. Results showed that BDNF and TrkB were widely expressed in all layers of visual cortex in young and old cats. Compared with the young group, the density and intensity of BDNF and TrkB positive cells in each layer of primary visual cortex in the old group decreased significantly (P < 0.01). The findings indicate that the expression levels of BDNF and TrkB in the primary visual cortex of cats decrease with age, suggesting that the change of BDNF-TrkB signal pathway caused by the weakening of brain-derived neurotrophic factor activity may be one of the important reasons for the decline of visual function.

Blue Light-Induced Retinal Neuronal Injury and Amelioration by Commercially Available Blue Light-Blocking Lenses.

Blue light exposure-induced retinal damage has been extensively studied. Although many in vitro studies have shown the benefits of blue light-blocking lenses (BBL) there have been few comprehensive in vivo studies to assess the effects of BBL. We investigated the influence of blue light exposure using light-emitting diodes on retinal histology and visual cortex neurons in rodents. We also considered whether retinal and cortical changes induced by blue light could be ameliorated with blue light-blocking lenses. A total of n = 24 (n = 6 in each group; control, light exposure without lenses, two different BBLs)) male Wistar rats were subjected to blue light exposure (LEDs, 450–500 lux) without or with BBLs (400–490 nm) for 28 days on a 12:12 h light–dark cycle. Histological analysis of retinae revealed apoptosis and necrosis of the retinal pigment epithelium (RPE), photoreceptors, and inner retina in the light exposure (LE) group, along with increase caspase-3 immunostaining in the ganglion cell layer (p < 0.001). BBL groups showed less caspase-3 immunostaining compared with the LE group (p < 0.001). V1-L5PNs (primary visual cortex layer 5 pyramidal neurons) demonstrated reduced branching and intersections points for apical (p < 0.001) and basal (p < 0.05) dendrites following blue light exposure. Blue light-blocking lenses significantly improved the number of basal branching points compared with the LE group. Our study shows that prolonged exposure to high levels of blue light pose a significant hazard to the visual system resulting in damage to the retina with the associated remodeling of visual cortex neurons. BBL may offer moderate protection against exposure to high levels of blue light.

Contributed Session II: Motion/direction-sensitive thalamic neurons project extensively to the middle layers of primary visual cortex

The motion/direction-sensitive and location-sensitive neurons are two major functional types in mouse visual thalamus that project to the primary visual cortex (V1). It has been proposed that the motion/direction-sensitive neurons mainly target the superficial layers in V1, in contrast to the location-sensitive neurons which mainly target the middle layers. Here, by imaging calcium activities of motion/direction-sensitive and location-sensitive axons in V1, we find no evidence for these cell-type specific laminar biases at population level. Furthermore, using a novel approach to reconstruct single-axon structures with identified in vivo response types, we show that, at single-axon level, the motion/direction-sensitive axons have middle layer preferences and project more densely to the middle layers than the location-sensitive axons. Overall, our results demonstrate that Motion/direction-sensitive thalamic neurons project extensively to the middle layers of V1, challenging the current view of the thalamocortical organizations in the mouse visual system.

Differential Effect of Anesthesia on Visual Cortex Neurons with Diverse Population Coupling

Cortical neurons display diverse firing patterns and synchronization properties. How anesthesia alters the firing response of different neuron groups relevant for sensory information processing is unclear. Here we investigated the graded effect of anesthesia on spontaneous and visual flash-induced spike activity of different neuron groups classified based on their spike waveform, firing rate, and population coupling (the extent neurons conform to population spikes). Single-unit activity was measured from multichannel extracellular recordings in deep layers of primary visual cortex of freely moving rats in wakefulness and at three concentrations of desflurane. Anesthesia generally decreased firing rate and increased population coupling and burstiness of neurons. Population coupling and firing rate became more correlated and the pairwise correlation between neurons became more predictable by their population coupling in anesthesia. During wakefulness, visual stimulation increased firing rate; this effect was the largest and the most prolonged in neurons that exhibited high population coupling and high firing rate. During anesthesia, the early increase in firing rate (20–150 ms post-stimulus) of these neurons was suppressed, their spike timing was delayed and split into two peaks. The late response (200–400 ms post-stimulus) of all neurons was also suppressed. We conclude that anesthesia alters the visual response of primarily high-firing highly coupled neurons, which may interfere with visual sensory processing. The increased association of population coupling and firing rate during anesthesia suggests a decrease in sensory information content.

A Quantitative Comparison of Inhibitory Interneuron Size and Distribution between Mouse and Macaque V1, Using Calcium-Binding Proteins.

The mouse is a useful and popular model for studying of visual cortical function. To facilitate the translation of results from mice to primates, it is important to establish the extent of cortical organization equivalence between species and to identify possible differences. We focused on the different types of interneurons as defined by calcium-binding protein (CBP) expression in the layers of primary visual cortex (V1) in mouse and rhesus macaque. CBPs parvalbumin (PV), calbindin (CB), and calretinin (CR) provide a standard, largely nonoverlapping, labeling scheme in macaque, with preserved corresponding morphologies in mouse, despite a slightly higher overlap. Other protein markers, which are relevant in mouse, are not preserved in macaque. We fluorescently tagged CBPs in V1 of both species, using antibodies raised against preserved aminoacid sequences. Our data demonstrate important similarities between the expression patterns of interneuron classes in the different layers between rodents and primates. However, in macaque, expression of PV and CB is more abundant, CR expression is lower, and the laminar distribution of interneuron populations is more differentiated. Our results reveal an integrated view of interneuron types that provides a basis for translating results from rodents to primates, and suggest a reconciliation of previous results.

Threat Anticipation in Pulvinar and in Superficial Layers of Primary Visual Cortex (V1). Evidence from Layer-Specific Ultra-High Field 7T fMRI.

The perceptual system gives priority to threat-relevant signals with survival value. In addition to the processing initiated by sensory inputs of threat signals, prioritization of threat signals may also include processes related to threat anticipation. These neural mechanisms remain largely unknown. Using ultra-high-field 7 tesla (7T) fMRI, we show that anticipatory processing takes place in the early stages of visual processing, specifically in the pulvinar and V1. When anticipation of a threat-relevant fearful face target triggered false perception of not-presented target, there was enhanced activity in the pulvinar as well as in the V1 superficial-cortical-depth (layers 1-3). The anticipatory activity was absent in the LGN or higher visual cortical areas (V2-V4). The effect in V1 was specific to the perception of fearful face targets and did not generalize to happy face targets. A preliminary analysis showed that the connectivity between the pulvinar and V1 superficial-cortical-depth was enhanced during false perception of threat, indicating that the pulvinar and V1 may interact in preparation of anticipated threat. The anticipatory processing supported by the pulvinar and V1 may play an important role in non-sensory-input-driven anxiety states.

Cortical State Fluctuations across Layers of V1 during Visual Spatial Perception

SUMMARYMany factors modulate the state of cortical activity, but the importance of cortical state variability for sensory perception remains debated. We trained mice to detect spatially localized visual stimuli and simultaneously measured local field potentials and excitatory and inhibitory neuron populations across layers of primary visual cortex (V1). Cortical states with low spontaneous firing and correlations in excitatory neurons, and suppression of 3- to 7-Hz oscillations in layer 4, accurately predicted single-trial visual detection. Our results show that cortical states exert strong effects at the initial stage of cortical processing in V1 and can play a prominent role for visual spatial behavior in mice.

Intracellular, In Vivo, Dynamics of Thalamocortical Synapses in Visual Cortex.

Seminal studies of the thalamocortical circuit in the visual system of the cat have been central to our understanding of sensory encoding. However, thalamocortical synaptic properties remain poorly understood. We used paired recordings, in the lateral geniculate nucleus (LGN) and primary visual cortex (V1), to provide the first in vivo characterization of sensory-driven thalamocortical potentials in V1. The amplitudes of EPSPs we characterized were smaller than those previously reported in vitro Consistent with prior findings, connected LGN-V1 pairs were only found when their receptive fields (RFs) overlapped, and the probability of connection increased steeply with degree of RF overlap and response similarity. However, surprisingly, we found no relationship between EPSP amplitudes and the similarity of RFs or responses, suggesting different connectivity models for intracortical and thalamocortical circuits. Putative excitatory regular-spiking (RS) and inhibitory fast-spiking (FS) V1 cells had similar EPSP characteristics, showing that in the visual system, feedforward excitation and inhibition are driven with equal strength by the thalamus. Similar to observations in the somatosensory cortex, FS V1 cells received less specific input from LGN. Finally, orientation tuning in V1 was not inherited from single presynaptic LGN cells, suggesting that it must emerge exclusively from the combined input of all presynaptic LGN cells. Our results help to decipher early visual encoding circuits and have immediate utility in providing physiological constraints to computational models of the visual system.SIGNIFICANCE STATEMENT To understand how the brain encodes the visual environment, we must understand the transfer of visual signals between various regions of the brain. Therefore, understanding synaptic dynamics is critical to our understanding of sensory encoding. This study provides the first characterization of visually evoked synaptic potentials between the visual thalamus and visual cortex in an intact animal. To record these potentials, we simultaneously recorded the extracellular potential of presynaptic thalamic cells and the intracellular potential of postsynaptic cortical cells in input layers of primary visual cortex. Our characterization of synaptic potentials in vivo disagreed with prior findings in vitro This study will increase our understanding of thalamocortical circuits and will improve computational models of visual encoding.

Visually Evoked 3-5 Hz Membrane Potential Oscillations Reduce the Responsiveness of Visual Cortex Neurons in Awake Behaving Mice.

Low-frequency membrane potential (Vm) oscillations were once thought to only occur in sleeping and anesthetized states. Recently, low-frequency Vm oscillations have been described in inactive awake animals, but it is unclear whether they shape sensory processing in neurons and whether they occur during active awake behavioral states. To answer these questions, we performed two-photon guided whole-cell Vm recordings from primary visual cortex layer 2/3 excitatory and inhibitory neurons in awake mice during passive visual stimulation and performance of visual and auditory discrimination tasks. We recorded stereotyped 3-5 Hz Vm oscillations where the Vm baseline hyperpolarized as the Vm underwent high amplitude rhythmic fluctuations lasting 1-2 s in duration. When 3-5 Hz Vm oscillations coincided with visual cues, excitatory neuron responses to preferred cues were significantly reduced. Despite this disruption to sensory processing, visual cues were critical for evoking 3-5 Hz Vm oscillations when animals performed discrimination tasks and passively viewed drifting grating stimuli. Using pupillometry and animal locomotive speed as indicators of arousal, we found that 3-5 Hz oscillations were not restricted to unaroused states and that they occurred equally in aroused and unaroused states. Therefore, low-frequency Vm oscillations play a role in shaping sensory processing in visual cortical neurons, even during active wakefulness and decision making.SIGNIFICANCE STATEMENT A neuron's membrane potential (Vm) strongly shapes how information is processed in sensory cortices of awake animals. Yet, very little is known about how low-frequency Vm oscillations influence sensory processing and whether they occur in aroused awake animals. By performing two-photon guided whole-cell recordings from layer 2/3 excitatory and inhibitory neurons in the visual cortex of awake behaving animals, we found visually evoked stereotyped 3-5 Hz Vm oscillations that disrupt excitatory responsiveness to visual stimuli. Moreover, these oscillations occurred when animals were in high and low arousal states as measured by animal speed and pupillometry. These findings show, for the first time, that low-frequency Vm oscillations can significantly modulate sensory signal processing, even in awake active animals.

The Significance of Memory in Sensory Cortex

Early sensory cortex is typically investigated in response to sensory stimulation, masking the contribution of internal signals. Recently, van Kerkoerle and colleagues reported that attention and memory signals segregate from sensory signals within specific layers of primary visual cortex, providing insight into the role of internal signals in sensory processing.

The importance of constructive feedback: Implications of top-down regulation in the development of neural circuits.

Neural circuits in sensory pathways develop through a general strategy of overproduction of synapses followed by activity-driven pruning to fine-tune connectivity for optimal function. The early visual pathway, consisting of the retina → visual thalamus → primary visual cortex, has served for decades as a powerful model system for probing the mechanisms and logic of this process. In addition to these feedforward projections, the early visual pathway also includes a substantial feedback component in the form of corticothalamic projections from the deepest layer of primary visual cortex. The role of this feedback in visual processing has been studied extensively in mature animals, yet historically, its role in development has received comparatively little attention. Recent technological advances allowing for selective manipulation of neural activity in development led to the uncovering of a role for feedback in guiding the refinement of the forward projection from retina to visual thalamus. Here we discuss the implications of feedback exerting influence on the development of sensory pathways. We propose several possible advantages to constructing neural circuits with top-down regulation, and discuss the potential significance of this finding for certain neurologic disorders.

Modular Representation of Luminance Polarity in the Superficial Layers of Primary Visual Cortex

The spatial arrangement of luminance increments (ON) and decrements (OFF) falling on the retina provides a wealth of information used by central visual pathways to construct coherent representations of visual scenes. But how the polarity of luminance change is represented in the activity of cortical circuits remains unclear. Using wide-field epifluorescence and two-photon imaging we demonstrate a robust modular representation of luminance polarity (ON or OFF) in the superficial layers of ferret primary visual cortex. Polarity-specific domains are found with both uniform changes in luminance and single light/dark edges, and include neurons selective for orientation and direction of motion. The integration of orientation and polarity preference is evident in the selectivity and discrimination capabilities of most layer 2/3 neurons. We conclude that polarity selectivity is an integral feature of layer 2/3 neurons, ensuring that the distinction between light and dark stimuli is available for further processing in downstream extrastriate areas.

The role of the different layers of primary visual cortex in working memory

Imaging studies have revealed a neuronal correlate of working memory in primary visual cortex (Harrison & Tong, Nature, 2009). However, it is unknown if working memories influence spiking activity in the primary visual cortex. To address this question, we recorded neuronal activity in the primary visual cortex of monkeys trained to perform attentional and working memory tasks with a probe that records activity in all the cortical layers. We found a consistent working memory trace in the spiking activity in the superficial and deep layers of monkey V1, and only a weak memory representation in input layer 4. This V1 memory trace could be disrupted with a visual mask, but it then quickly recovered. The advantage of the laminar probe is that is also gives insight into the current-source density, which reveals the putative synaptic sources of memory activity. The current-source density measurements revealed a characteristic signature of feedback processing with putative synaptic inputs in the superficial and deep layers for working memory. This signature resembles the signature of selective attention, supporting the view that top-down modulation of activity in primary visual cortex underlies both working memory and attention. Our results provide new insights into the role of early visual cortex in working memory.

Frequency-band signatures of visual responses to naturalistic input in ferret primary visual cortex during free viewing

Neuronal firing responses in visual cortex reflect the statistics of visual input and emerge from the interaction with endogenous network dynamics. Artificial visual stimuli presented to animals in which the network dynamics were constrained by anesthetic agents or trained behavioral tasks have provided fundamental understanding of how individual neurons in primary visual cortex respond to input. In contrast, very little is known about the mesoscale network dynamics and their relationship to microscopic spiking activity in the awake animal during free viewing of naturalistic visual input. To address this gap in knowledge, we recorded local field potential (LFP) and multiunit activity (MUA) simultaneously in all layers of primary visual cortex (V1) of awake, freely viewing ferrets presented with naturalistic visual input (nature movie clips). We found that naturalistic visual stimuli modulated the entire oscillation spectrum; low frequency oscillations were mostly suppressed whereas higher frequency oscillations were enhanced. In average across all cortical layers, stimulus-induced change in delta and alpha power negatively correlated with the MUA responses, whereas sensory-evoked increases in gamma power positively correlated with MUA responses. The time-course of the band-limited power in these frequency bands provided evidence for a model in which naturalistic visual input switched V1 between two distinct, endogenously present activity states defined by the power of low (delta, alpha) and high (gamma) frequency oscillatory activity. Therefore, the two mesoscale activity states delineated in this study may define the degree of engagement of the circuit with the processing of sensory input.

Cortical origin of Up state onsets and offsets in anesthetized rats

Slow rhythms (< 1 Hz) where Up states of sustained neural activity alternate with almost quiescent Down states, are similarly expressed by mammal brains during slow-wave-sleep (SWS) and under anesthesia [1]. Although much effort has been devoted to uncover the physiological origin of such slow oscillations (SO), it is still debated whether Up state onsets in this quasi-periodic bouncing of neural activity are driven by cortico-cortical synaptic interactions [1-3], or if they are due to the interplay between thalamic nuclei and cerebral cortex [4,5]. We addressed this issue probing neuronal and synaptic activity across all layers of primary visual cortex (V1) of rats, which showed stable Up/Down SO when anesthetized with ketamine and medetomidine. During Up states, maximum multi-unit activity (MUA) was found at a depth of 880 ± 80 μm (mean ± SD, n = 14) from cortical surface, corresponding to upper layer 5. To be able to classify events as supra/infragranular and thus to accurately identify layer 4 position, we resorted to a classical current source density (CSD) analysis looking at the earliest synaptic activation following visual stimulation [6]. This, together with a principal component analysis (PCA), allowed us to characterize Up state onsets at high spatiotemporal resolution as a stereotyped sequence of events. Firstly, in deep layers (1260 ± 80 μm, mean ± SD, n = 14) a CSD sink appeared highlighting the arrival of synaptic input, always followed after 10 ms by a MUA onset at same depths. After a variable delay between 0 and 40 ms, MUA increased in upper layer 5 and propagated to supragranular layers. Interestingly, such upward spreading of activity from deep to more superficial layers was not altered by the inactivation of visual thalamus obtained injecting TTX in LGN (lateral geniculate nucleus). Downward transitions from Up to Down states, showed a different timing of MUA offsets across layers. We found both positive and negative time lags between MUA inactivation of upper layer 5 and deeper layers, highlighting only a weak correlation between these two events. In layer 5-6, CSD sinks followed with a rather precise delay of 50 ms MUA offsets at the same depth, supporting the hypothesis of a network whose preferred state is the quiescent one, despite a steady synaptic input continue to be received. Even for downward transitions the chain of events was unchanged injecting TTX in the thalamus. The collected evidence for both Up state initiation and termination unambiguously reserves for the thalamus a marginal role, pointing out cortico-cortical connectivity as the main drive for Up/Down SO. Such cortico-cortical chat takes place in a state-dependent manner.

Laminar dependence of neuronal correlations in visual cortex

Neuronal responses are correlated on a range of timescales. Correlations can affect population coding and may play an important role in cortical function. Correlations are known to depend on stimulus drive, behavioral context, and experience, but the mechanisms that determine their properties are poorly understood. Here we make use of the laminar organization of cortex, with its variations in sources of input, local circuit architecture, and neuronal properties, to test whether networks engaged in similar functions but with distinct properties generate different patterns of correlation. We find that slow timescale correlations are prominent in the superficial and deep layers of primary visual cortex (V1) of macaque monkeys, but near zero in the middle layers. Brief timescale correlation (synchrony), on the other hand, was slightly stronger in the middle layers of V1, although evident at most cortical depths. Laminar variations were also apparent in the power of the local field potential, with a complementary pattern for low frequency (<10 Hz) and gamma (30-50 Hz) power. Recordings in area V2 revealed a laminar dependence similar to V1 for synchrony, but slow timescale correlations were not different between the input layers and nearby locations. Our results reveal that cortical circuits in different laminae can generate remarkably different patterns of correlations, despite being tightly interconnected.

Examining Local Network Processing using Multi-contact Laminar Electrode Recording

Cortical layers are ubiquitous structures throughout neocortex that consist of highly recurrent local networks. In recent years, significant progress has been made in our understanding of differences in response properties of neurons in different cortical layers, yet there is still a great deal left to learn about whether and how neuronal populations encode information in a laminar-specific manner. Existing multi-electrode array techniques, although informative for measuring responses across many millimeters of cortical space along the cortical surface, are unsuitable to approach the issue of laminar cortical circuits. Here, we present our method for setting up and recording individual neurons and local field potentials (LFPs) across cortical layers of primary visual cortex (V1) utilizing multi-contact laminar electrodes (Figure 1; Plextrode U-Probe, Plexon Inc). The methods included are recording device construction, identification of cortical layers, and identification of receptive fields of individual neurons. To identify cortical layers, we measure the evoked response potentials (ERPs) of the LFP time-series using full-field flashed stimuli. We then perform current-source density (CSD) analysis to identify the polarity inversion accompanied by the sink-source configuration at the base of layer 4 (the sink is inside layer 4, subsequently referred to as granular layer). Current-source density is useful because it provides an index of the location, direction, and density of transmembrane current flow, allowing us to accurately position electrodes to record from all layers in a single penetration.