The influence of electrode types to the visually induced gamma oscillations in mouse primary visual cortex.

The local field potential (LFP) is an extracellular electrical signal associated with neural ensemble input and dendritic signaling. Previous studies have linked gamma band oscillations of the LFP in cortical circuits to sensory stimuli encoding, attention, memory, and perception. Inconsistent results regarding gamma tuning for visual features were reported, but it remains unclear whether these discrepancies are due to variations in electrode properties. Specifically, the surface area and impedance of the electrode are important characteristics in LFP recording. To comprehensively address these issues, we conducted an electrophysiological study in the V1 region of lightly anesthetized mice using two types of electrodes: one with higher impedance (1 MΩ) and a sharp tip (10 µm), while the other had lower impedance (100 KΩ) but a thicker tip (200 µm). Our findings demonstrate that gamma oscillations acquired by sharp-tip electrodes were significantly stronger than those obtained from thick-tip electrodes. Regarding size tuning, most gamma power exhibited surround suppression at larger gratings when recorded from sharp-tip electrodes. However, the majority showed enhanced gamma power at larger gratings when recorded from thick-tip electrodes. Therefore, our study suggests that microelectrode parameters play a significant role in accurately recording gamma oscillations and responsive tuning to sensory stimuli.

Nonuniform and pathway-specific laminar processing of spatial frequencies in the primary visual cortex of primates.

The neocortex comprises six cortical layers that play a crucial role in information processing; however, it remains unclear whether laminar processing is consistent across all regions within a single cortex. In this study, we demonstrate diverse laminar response patterns in the primary visual cortex (V1) of three male macaque monkeys when exposed to visual stimuli at different spatial frequencies (SFs). These response patterns can be categorized into two groups. One group exhibit suppressed responses in the output layers for all SFs, while the other type shows amplified responses specifically at high SFs. Further analysis suggests that both magnocellular (M) and parvocellular (P) pathways contribute to the suppressive effect through feedforward mechanisms, whereas amplification is specific to local recurrent mechanisms within the parvocellular pathway. These findings highlight the non-uniform distribution of neural mechanisms involved in laminar processing and emphasize how pathway-specific amplification selectively enhances representations of high-SF information in primate V1.

A non-image-forming visual circuit mediates the innate fear of heights in male mice.

The neural basis of fear of heights remains largely unknown. In this study, we investigated the fear response to heights in male mice and observed characteristic aversive behaviors resembling human height vertigo. We identified visual input as a critical factor in mouse reactions to heights, while peripheral vestibular input was found to be nonessential for fear of heights. Unexpectedly, we found that fear of heights in naïve mice does not rely on image-forming visual processing by the primary visual cortex. Instead, a subset of neurons in the ventral lateral geniculate nucleus (vLGN), which connects to the lateral/ventrolateral periaqueductal gray (l/vlPAG), drives the expression of fear associated with heights. Additionally, we observed that a subcortical visual pathway linking the superior colliculus to the lateral posterior thalamic nucleus inhibits the defensive response to height threats. These findings highlight a rapid fear response to height threats through a subcortical visual and defensive pathway from the vLGN to the l/vlPAG.

Encoding luminance surfaces in the visual cortex of mice and monkeys: difference in responses to edge and center.

Luminance and spatial contrast provide information on the surfaces and edges of objects. We investigated neural responses to black and white surfaces in the primary visual cortex (V1) of mice and monkeys. Unlike primates that use their fovea to inspect objects with high acuity, mice lack a fovea and have low visual acuity. It thus remains unclear whether monkeys and mice share similar neural mechanisms to process surfaces. The animals were presented with white or black surfaces and the population responses were measured at high spatial and temporal resolution using voltage-sensitive dye imaging. In mice, the population response to the surface was not edge-dominated with a tendency to center-dominance, whereas in monkeys the response was edge-dominated with a "hole" in the center of the surface. The population response to the surfaces in both species exhibited suppression relative to a grating stimulus. These results reveal the differences in spatial patterns to luminance surfaces in the V1 of mice and monkeys and provide evidence for a shared suppression process relative to grating.

Brightness illusions drive a neuronal response in the primary visual cortex under top-down modulation.

Brightness illusions are a powerful tool in studying vision, yet their neural correlates are poorly understood. Based on a human paradigm, we presented illusory drifting gratings to mice. Primary visual cortex (V1) neurons responded to illusory gratings, matching their direction selectivity for real gratings, and they tracked the spatial phase offset between illusory and real gratings. Illusion responses were delayed compared to real gratings, in line with the theory that processing illusions requires feedback from higher visual areas (HVAs). We provide support for this theory by showing a reduced V1 response to illusions, but not real gratings, following HVAs optogenetic inhibition. Finally, we used the pupil response (PR) as an indirect perceptual report and showed that the mouse PR matches the human PR to perceived luminance changes. Our findings resolve debates over whether V1 neurons are involved in processing illusions and highlight the involvement of feedback from HVAs.

Stimulus-dependent differences in cortical versus subcortical contributions to visual detection in mice.

The primary visual cortex (V1) and the superior colliculus (SC) both occupy stations early in the processing of visual information. They have long been thought to perform distinct functions, with the V1 supporting the perception of visual features and the SC regulating orienting to visual inputs. However, growing evidence suggests that the SC supports the perception of many of the same visual features traditionally associated with the V1. To distinguish V1 and SC contributions to visual processing, it is critical to determine whether both areas causally contribute to the detection of specific visual stimuli. Here, mice reported changes in visual contrast or luminance near their perceptual threshold while white noise patterns of optogenetic stimulation were delivered to V1 or SC inhibitory neurons. We then performed a reverse correlation analysis on the optogenetic stimuli to estimate a neuronal-behavioral kernel (NBK), a moment-to-moment estimate of the impact of V1 or SC inhibition on stimulus detection. We show that the earliest moments of stimulus-evoked activity in the SC are critical for the detection of both luminance and contrast changes. Strikingly, there was a robust stimulus-aligned modulation in the V1 contrast-detection NBK but no sign of a comparable modulation for luminance detection. The data suggest that behavioral detection of visual contrast depends on both V1 and SC spiking, whereas mice preferentially use SC activity to detect changes in luminance. Electrophysiological recordings showed that neurons in both the SC and V1 responded strongly to both visual stimulus types, while the reverse correlation analysis reveals when these neuronal signals actually contribute to visually guided behaviors.

Altered functional connectivity strength of primary visual cortex in subjects with thyroid-associated ophthalmopathy.

Our objective was to explore the disparities in the intrinsic functional connectivity (FC) patterns of primary visual cortex (V1) between patients with thyroid-associated ophthalmopathy (TAO) and healthy controls (HCs) utilizing resting-state functional MRI. Twenty-one patients with TAO (14 males and 7 females; mean age: 54.17 ±â€…4.83 years) and 21 well-matched HCs (14 males and 7 females; mean age: 55.17 ±â€…5.37 years) underwent functional MRI scans in the resting-state. We assessed modifications in the intrinsic FC patterns of the V1 in TAO patients using the FC method. Subsequently, the identified alterations in FC regions in the analysis were selected as classification features to distinguish TAO patients from HCs through the support vector machine (SVM) method. The results indicated that, in comparison to HCs, patients with TAO exhibited notably reduced FC values between the left V1 and the bilateral calcarine (CAL), lingual gyrus (LING) and superior occipital gyrus, as well as between the right V1 and the bilateral CAL/LING and the right cerebellum. Furthermore, the SVM classification model based on FC maps demonstrated effective performance in distinguishing TAO patients from HCs, achieving an accuracy of 61.9% using the FC of the left V1 and 64.29% using the FC of the right V1. Our study revealed that patients with TAO manifested disruptions in FC between the V1 and higher visual regions during rest. This might indicate that TAO patients could present with impaired top-down modulations, visual imagery and vision-motor function. These insights could be valuable in understanding the underlying neurobiological mechanisms of vision impairment in individuals with TAO.

Are we aware of neural activity in primary visual cortex? A neuropsychological case study.

OBJECTIVE: According to a seminal hypothesis stated by Crick and Koch in 1995, one is not aware of neural activity in primary visual cortex (V1) because this region lacks reciprocal connections with prefrontal cortex (PFC). METHODS: We provide here a neuropsychological illustration of this hypothesis in a patient with a very rare form of cortical blindness: ventral and dorsal cortical pathways were lesioned bilaterally while V1 areas were partially preserved. RESULTS: Visual stimuli escaped conscious perception but still activated V1 regions that were functionally disconnected from PFC. INTERPRETATION: These results are consistent with the hypothesis of a causal role of PFC in visual awareness.

Stimulus-dependent synaptic plasticity underlies neuronal circuitry refinement in the mouse primary visual cortex.

Perceptual learning improves our ability to interpret sensory stimuli present in our environment through experience. Despite its importance, the underlying mechanisms that enable perceptual learning in our sensory cortices are still not fully understood. In this study, we used in vivo two-photon imaging to investigate the functional and structural changes induced by visual stimulation in the mouse primary visual cortex (V1). Our results demonstrate that repeated stimulation leads to a refinement of V1 circuitry by decreasing the number of responsive neurons while potentiating their response. At the synaptic level, we observe a reduction in the number of dendritic spines and an overall increase in spine AMPA receptor levels in the same subset of neurons. In addition, visual stimulation induces synaptic potentiation in neighboring spines within individual dendrites. These findings provide insights into the mechanisms of synaptic plasticity underlying information processing in the neocortex.

Cortico-cortical feedback engages active dendrites in visual cortex.

Sensory processing in the neocortex requires both feedforward and feedback information flow between cortical areas1. In feedback processing, higher-level representations provide contextual information to lower levels, and facilitate perceptual functions such as contour integration and figure-ground segmentation2,3. However, we have limited understanding of the circuit and cellular mechanisms that mediate feedback influence. Here we use long-range all-optical connectivity mapping in mice to show that feedback influence from the lateromedial higher visual area (LM) to the primary visual cortex (V1) is spatially organized. When the source and target of feedback represent the same area of visual space, feedback is relatively suppressive. By contrast, when the source is offset from the target in visual space, feedback is relatively facilitating. Two-photon calcium imaging data show that this facilitating feedback is nonlinearly integrated in the apical tuft dendrites of V1 pyramidal neurons: retinotopically offset (surround) visual stimuli drive local dendritic calcium signals indicative of regenerative events, and two-photon optogenetic activation of LM neurons projecting to identified feedback-recipient spines in V1 can drive similar branch-specific local calcium signals. Our results show how neocortical feedback connectivity and nonlinear dendritic integration can together form a substrate to support both predictive and cooperative contextual interactions.

Spontaneous variations in arousal modulate subsequent visual processing and local field potential dynamics in the ferret during quiet wakefulness.

Behavioral states affect neuronal responses throughout the cortex and influence visual processing. Quiet wakefulness (QW) is a behavioral state during which subjects are quiescent but awake and connected to the environment. Here, we examined the effects of pre-stimulus arousal variability on post-stimulus neural activity in the primary visual cortex and posterior parietal cortex in awake ferrets, using pupil diameter as an indicator of arousal. We observed that the power of stimuli-induced alpha (8-12 Hz) decreases when the arousal level increases. The peak of alpha power shifts depending on arousal. High arousal increases inter- and intra-areal coherence. Using a simplified model of laminar circuits, we show that this connectivity pattern is compatible with feedback signals targeting infragranular layers in area posterior parietal cortex and supragranular layers in V1. During high arousal, neurons in V1 displayed higher firing rates at their preferred orientations. Broad-spiking cells in V1 are entrained to high-frequency oscillations (>80 Hz), whereas narrow-spiking neurons are phase-locked to low- (12-18 Hz) and high-frequency (>80 Hz) rhythms. These results indicate that the variability and sensitivity of post-stimulus cortical responses and coherence depend on the pre-stimulus behavioral state and account for the neuronal response variability observed during repeated stimulation.

Novel stimuli evoke excess activity in the mouse primary visual cortex.

To explore how neural circuits represent novel versus familiar inputs, we presented mice with repeated sets of images with novel images sparsely substituted. Using two-photon calcium imaging to record from layer 2/3 neurons in the mouse primary visual cortex, we found that novel images evoked excess activity in the majority of neurons. This novelty response rapidly emerged, arising with a time constant of 2.6 ± 0.9 s. When a new image set was repeatedly presented, a majority of neurons had similarly elevated activity for the first few presentations, which decayed to steady state with a time constant of 1.4 ± 0.4 s. When we increased the number of images in the set, the novelty response's amplitude decreased, defining a capacity to store ∼15 familiar images under our conditions. These results could be explained quantitatively using an adaptive subunit model in which presynaptic neurons have individual tuning and gain control. This result shows that local neural circuits can create different representations for novel versus familiar inputs using generic, widely available mechanisms.

Optimizing intact skull intrinsic signal imaging for subsequent targeted electrophysiology across mouse visual cortex.

Understanding brain function requires repeatable measurements of neural activity across multiple scales and multiple brain areas. In mice, large scale cortical neural activity evokes hemodynamic changes readily observable with intrinsic signal imaging (ISI). Pairing ISI with visual stimulation allows identification of primary visual cortex (V1) and higher visual areas (HVAs), typically through cranial windows that thin or remove the skull. These procedures can diminish long-term mechanical and physiological stability required for delicate electrophysiological measurements made weeks to months after imaging (e.g., in subjects undergoing behavioral training). Here, we optimized and directly validated an intact skull ISI system in mice. We first assessed how imaging quality and duration affect reliability of retinotopic maps in V1 and HVAs. We then verified ISI map retinotopy in V1 and HVAs with targeted, multi-site electrophysiology several weeks after imaging. Reliable ISI maps of V1 and multiple HVAs emerged with ~ 60 trials of imaging (65 ± 6 min), and these showed strong correlation to local field potential (LFP) retinotopy in superficial cortical layers (r2 = 0.74-0.82). This system is thus well-suited for targeted, multi-area electrophysiology weeks to months after imaging. We provide detailed instructions and code for other researchers to implement this system.

Synaptic connectivity to L2/3 of primary visual cortex measured by two-photon optogenetic stimulation.

Understanding cortical microcircuits requires thorough measurement of physiological properties of synaptic connections formed within and between diverse subclasses of neurons. Towards this goal, we combined spatially precise optogenetic stimulation with multicellular recording to deeply characterize intralaminar and translaminar monosynaptic connections to supragranular (L2/3) neurons in the mouse visual cortex. The reliability and specificity of multiphoton optogenetic stimulation were measured across multiple Cre lines, and measurements of connectivity were verified by comparison to paired recordings and targeted patching of optically identified presynaptic cells. With a focus on translaminar pathways, excitatory and inhibitory synaptic connections from genetically defined presynaptic populations were characterized by their relative abundance, spatial profiles, strength, and short-term dynamics. Consistent with the canonical cortical microcircuit, layer 4 excitatory neurons and interneurons within L2/3 represented the most common sources of input to L2/3 pyramidal cells. More surprisingly, we also observed strong excitatory connections from layer 5 intratelencephalic neurons and potent translaminar inhibition from multiple interneuron subclasses. The hybrid approach revealed convergence to and divergence from excitatory and inhibitory neurons within and across cortical layers. Divergent excitatory connections often spanned hundreds of microns of horizontal space. In contrast, divergent inhibitory connections were more frequently measured from postsynaptic targets near each other.

Coding strategy for surface luminance switches in the primary visual cortex of the awake monkey.

Both surface luminance and edge contrast of an object are essential features for object identification. However, cortical processing of surface luminance remains unclear. In this study, we aim to understand how the primary visual cortex (V1) processes surface luminance information across its different layers. We report that edge-driven responses are stronger than surface-driven responses in V1 input layers, but luminance information is coded more accurately by surface responses. In V1 output layers, the advantage of edge over surface responses increased eight times and luminance information was coded more accurately at edges. Further analysis of neural dynamics shows that such substantial changes for neural responses and luminance coding are mainly due to non-local cortical inhibition in V1's output layers. Our results suggest that non-local cortical inhibition modulates the responses elicited by the surfaces and edges of objects, and that switching the coding strategy in V1 promotes efficient coding for luminance.

Increasing neural network robustness improves match to macaque V1 eigenspectrum, spatial frequency preference and predictivity.

Task-optimized convolutional neural networks (CNNs) show striking similarities to the ventral visual stream. However, human-imperceptible image perturbations can cause a CNN to make incorrect predictions. Here we provide insight into this brittleness by investigating the representations of models that are either robust or not robust to image perturbations. Theory suggests that the robustness of a system to these perturbations could be related to the power law exponent of the eigenspectrum of its set of neural responses, where power law exponents closer to and larger than one would indicate a system that is less susceptible to input perturbations. We show that neural responses in mouse and macaque primary visual cortex (V1) obey the predictions of this theory, where their eigenspectra have power law exponents of at least one. We also find that the eigenspectra of model representations decay slowly relative to those observed in neurophysiology and that robust models have eigenspectra that decay slightly faster and have higher power law exponents than those of non-robust models. The slow decay of the eigenspectra suggests that substantial variance in the model responses is related to the encoding of fine stimulus features. We therefore investigated the spatial frequency tuning of artificial neurons and found that a large proportion of them preferred high spatial frequencies and that robust models had preferred spatial frequency distributions more aligned with the measured spatial frequency distribution of macaque V1 cells. Furthermore, robust models were quantitatively better models of V1 than non-robust models. Our results are consistent with other findings that there is a misalignment between human and machine perception. They also suggest that it may be useful to penalize slow-decaying eigenspectra or to bias models to extract features of lower spatial frequencies during task-optimization in order to improve robustness and V1 neural response predictivity.

Multiple gamma rhythms carry distinct spatial frequency information in primary visual cortex.

Gamma rhythms in many brain regions, including the primary visual cortex (V1), are thought to play a role in information processing. Here, we report a surprising finding of 3 narrowband gamma rhythms in V1 that processed distinct spatial frequency (SF) signals and had different neural origins. The low gamma (LG; 25 to 40 Hz) rhythm was generated at the V1 superficial layer and preferred a higher SF compared with spike activity, whereas both the medium gamma (MG; 40 to 65 Hz), generated at the cortical level, and the high gamma HG; (65 to 85 Hz), originated precortically, preferred lower SF information. Furthermore, compared with the rates of spike activity, the powers of the 3 gammas had better performance in discriminating the edge and surface of simple objects. These findings suggest that gamma rhythms reflect the neural dynamics of neural circuitries that process different SF information in the visual system, which may be crucial for multiplexing SF information and synchronizing different features of an object.

Double-µPeriscope, a tool for multilayer optical recordings, optogenetic stimulations or both.

Intelligent behavior and cognitive functions in mammals depend on cortical microcircuits made up of a variety of excitatory and inhibitory cells that form a forest-like complex across six layers. Mechanistic understanding of cortical microcircuits requires both manipulation and monitoring of multiple layers and interactions between them. However, existing techniques are limited as to simultaneous monitoring and stimulation at different depths without damaging a large volume of cortical tissue. Here, we present a relatively simple and versatile method for delivering light to any two cortical layers simultaneously. The method uses a tiny optical probe consisting of two microprisms mounted on a single shaft. We demonstrate the versatility of the probe in three sets of experiments: first, two distinct cortical layers were optogenetically and independently manipulated; second, one layer was stimulated while the activity of another layer was monitored; third, the activity of thalamic axons distributed in two distinct cortical layers was simultaneously monitored in awake mice. Its simple-design, versatility, small-size, and low-cost allow the probe to be applied widely to address important biological questions.

Tightly coupled inhibitory and excitatory functional networks in the developing primary visual cortex.

Intracortical inhibition plays a critical role in shaping activity patterns in the mature cortex. However, little is known about the structure of inhibition in early development prior to the onset of sensory experience, a time when spontaneous activity exhibits long-range correlations predictive of mature functional networks. Here, using calcium imaging of GABAergic neurons in the ferret visual cortex, we show that spontaneous activity in inhibitory neurons is already highly organized into distributed modular networks before visual experience. Inhibitory neurons exhibit spatially modular activity with long-range correlations and precise local organization that is in quantitative agreement with excitatory networks. Furthermore, excitatory and inhibitory networks are strongly co-aligned at both millimeter and cellular scales. These results demonstrate a remarkable degree of organization in inhibitory networks early in the developing cortex, providing support for computational models of self-organizing networks and suggesting a mechanism for the emergence of distributed functional networks during development.

Traumatic brain injury to primary visual cortex produces long-lasting circuit dysfunction.

Primary sensory areas of the mammalian neocortex have a remarkable degree of plasticity, allowing neural circuits to adapt to dynamic environments. However, little is known about the effects of traumatic brain injury on visual circuit function. Here we used anatomy and in vivo electrophysiological recordings in adult mice to quantify neuron responses to visual stimuli two weeks and three months after mild controlled cortical impact injury to primary visual cortex (V1). We found that, although V1 remained largely intact in brain-injured mice, there was ~35% reduction in the number of neurons that affected inhibitory cells more broadly than excitatory neurons. V1 neurons showed dramatically reduced activity, impaired responses to visual stimuli and weaker size selectivity and orientation tuning in vivo. Our results show a single, mild contusion injury produces profound and long-lasting impairments in the way V1 neurons encode visual input. These findings provide initial insight into cortical circuit dysfunction following central visual system neurotrauma.