Optical imaging of the intrinsic signal as a tool to characterize orientation sensitivity in the primary visual cortex of the young mouse.

We employed intrinsic signal optical imaging (ISOI) to investigate orientation sensitivity bias in the visual cortex of young mice. Optical signals were recorded in response to the moving light gratings stimulating ipsi­, contra­ and binocular eye inputs. ISOI allowed visualization of cortical areas activated by gratings of specific orientation and temporal changes of light scatter during visual stimulation. These results confirmed ISOI as a reliable technique for imaging the activity of large populations of neurons in the mouse visual cortex. Our results revealed that the contralateral ocular input activated a larger area of the primary visual cortex than the ipsilateral input, and caused the highest response amplitudes of light scatter signals to all ocular inputs. Horizontal gratings moved in vertical orientation induced the most significant changes in light scatter when presented contralaterally and binocularly, surpassing stimulations by vertical or oblique gratings. These observations suggest dedicated integration mechanisms for the combined inputs from both eyes. We also explored the relationship between point luminance change (PLC) of grating stimuli and ISOI time courses under various orientations of movements of the gratings and ocular inputs, finding higher cross-correlation values for cardinal orientations and ipsilateral inputs. These findings suggested specific activation of different neuronal assemblies within the mouse's primary visual cortex by grating stimuli of the corresponding orientation. However, further investigations are needed to examine this summation hypothesis. Our study highlights the potential of optical imaging as a valuable tool for exploring functional­anatomical relationships in the mouse visual system.

In primary visual cortex fMRI responses to chromatic and achromatic stimuli are interdependent and predict contrast detection thresholds.

Chromatic and achromatic signals in primary visual cortex have historically been considered independent of each other but have since shown evidence of interdependence. Here, we investigated the combination of two components of a stimulus; an achromatic dynamically changing check background and a chromatic (L-M or S cone) target grating. We found that combinations of chromatic and achromatic signals in primary visual cortex were interdependent, with the dynamic range of responses to chromatic contrast decreasing as achromatic contrast increased. A contrast detection threshold study also revealed interdependence of background and target, with increasing chromatic contrast detection thresholds as achromatic background contrast increased. A model that incorporated a normalising effect of achromatic contrast on chromatic responses, but not vice versa, best predicted our V1 data as well as behavioural thresholds. Further along the visual hierarchy, the dynamic range of chromatic responses was maintained when compared to achromatic responses, which became increasingly compressive.

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.

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

Primary sensory cortices respond to crossmodal stimuli-for example, auditory responses are found in primary visual cortex (V1). However, it remains unclear whether these responses reflect sensory inputs or behavioral modulation through sound-evoked body movement. We address this controversy by showing that sound-evoked activity in V1 of awake mice can be dissociated into auditory and behavioral components with distinct spatiotemporal profiles. The auditory component began at approximately 27 ms, was found in superficial and deep layers and originated from auditory cortex. Sound-evoked orofacial movements correlated with V1 neural activity starting at approximately 80-100 ms and explained auditory frequency tuning. Visual, auditory and motor activity were expressed by different laminar profiles and largely segregated subsets of neuronal populations. During simultaneous audiovisual stimulation, visual representations remained dissociable from auditory-related and motor-related activity. This three-fold dissociability of auditory, motor and visual processing is central to understanding how distinct inputs to visual cortex interact to support vision.

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.

Transsynaptic Degeneration of Retinal Ganglion Cells Following Lesions to Primary Visual Cortex in Marmosets.

Purpose: A lesion to primary visual cortex (V1) in primates can produce retrograde transneuronal degeneration in the dorsal lateral geniculate nucleus (LGN) and retina. We investigated the effect of age at time of lesion on LGN volume and retinal ganglion cell (RGC) density in marmoset monkeys. Methods: Retinas and LGNs were obtained about 2 years after a unilateral left-sided V1 lesion as infants (n = 7) or young adult (n = 1). Antibodies against RBPMS were used to label all RGCs, and antibodies against CaMKII or GABAA receptors were used to label nonmidget RGCs. Cell densities were compared in the left and right hemiretina of each eye. The LGNs were stained with the nuclear marker NeuN or for Nissl substance. Results: In three animals lesioned within the first 2 postnatal weeks, the proportion of RGCs lost within 5 mm of the fovea was ∼twofold higher than after lesions at 4 or 6 weeks. There was negligible loss in the animal lesioned at 2 years of age. A positive correlation between RGC loss and LGN volume reduction was evident. No loss of CaMKII-positive or GABAA receptor-positive RGCs was apparent within 2 mm of the fovea in any of the retinas investigated. Conclusions: Susceptibility of marmoset RGCs to transneuronal degeneration is high at birth and declines over the first 6 postnatal weeks. High survival rates of CaMKII and GABAA receptor-positive RGCs implies that widefield and parasol cells are less affected by neonatal cortical lesions than are midget-pathway cells.

Dynamic fading memory and expectancy effects in the monkey primary visual cortex.

In order to investigate the involvement of the primary visual cortex (V1) in working memory (WM), parallel, multisite recordings of multi-unit activity were obtained from monkey V1 while the animals performed a delayed match-to-sample (DMS) task. During the delay period, V1 population firing rate vectors maintained a lingering trace of the sample stimulus that could be reactivated by intervening impulse stimuli that enhanced neuronal firing. This fading trace of the sample did not require active engagement of the monkeys in the DMS task and likely reflects the intrinsic dynamics of recurrent cortical networks in lower visual areas. This renders an active, attention-dependent involvement of V1 in the maintenance of WM contents unlikely. By contrast, population responses to the test stimulus depended on the probabilistic contingencies between sample and test stimuli. Responses to tests that matched expectations were reduced which agrees with concepts of predictive coding.

Predicting Single Neuron Responses of the Primary Visual Cortex with Deep Learning Model.

Modeling neuron responses to stimuli can shed light on next-generation technologies such as brain-chip interfaces. Furthermore, high-performing models can serve to help formulate hypotheses and reveal the mechanisms underlying neural responses. Here the state-of-the-art computational model is presented for predicting single neuron responses to natural stimuli in the primary visual cortex (V1) of mice. The algorithm incorporates object positions and assembles multiple models with different train-validation data, resulting in a 15%-30% improvement over the existing models in cross-subject predictions and ranking first in the SENSORIUM 2022 Challenge, which benchmarks methods for neuron-specific prediction based on thousands of images. Importantly, The model reveals evidence that the spatial organizations of V1 are conserved across mice. This model will serve as an important noninvasive tool for understanding and utilizing the response patterns of primary visual cortex neurons.

The logic of recurrent circuits in the primary visual cortex.

Recurrent cortical activity sculpts visual perception by refining, amplifying or suppressing visual input. However, the rules that govern the influence of recurrent activity remain enigmatic. We used ensemble-specific two-photon optogenetics in the mouse visual cortex to isolate the impact of recurrent activity from external visual input. We found that the spatial arrangement and the visual feature preference of the stimulated ensemble and the neighboring neurons jointly determine the net effect of recurrent activity. Photoactivation of these ensembles drives suppression in all cells beyond 30 µm but uniformly drives activation in closer similarly tuned cells. In nonsimilarly tuned cells, compact, cotuned ensembles drive net suppression, while diffuse, cotuned ensembles drive activation. Computational modeling suggests that highly local recurrent excitatory connectivity and selective convergence onto inhibitory neurons explain these effects. Our findings reveal a straightforward logic in which space and feature preference of cortical ensembles determine their impact on local recurrent activity.

Joint encoding of stimulus and decision in monkey primary visual cortex.

We investigated whether neurons in monkey primary visual cortex (V1) exhibit mixed selectivity for sensory input and behavioral choice. Parallel multisite spiking activity was recorded from area V1 of awake monkeys performing a delayed match-to-sample task. The monkeys had to make a forced choice decision of whether the test stimulus matched the preceding sample stimulus. The population responses evoked by the test stimulus contained information about both the identity of the stimulus and with some delay but before the onset of the motor response the forthcoming choice. The results of subspace identification analysis indicate that stimulus-specific and decision-related information coexists in separate subspaces of the high-dimensional population activity, and latency considerations suggest that the decision-related information is conveyed by top-down projections.

Disinhibition by VIP interneurons is orthogonal to cross-modal attentional modulation in primary visual cortex.

Attentional modulation of sensory processing is a key feature of cognition; however, its neural circuit basis is poorly understood. A candidate mechanism is the disinhibition of pyramidal cells through vasoactive intestinal peptide (VIP) and somatostatin (SOM)-positive interneurons. However, the interaction of attentional modulation and VIP-SOM disinhibition has never been directly tested. We used all-optical methods to bi-directionally manipulate VIP interneuron activity as mice performed a cross-modal attention-switching task. We measured the activities of VIP, SOM, and parvalbumin (PV)-positive interneurons and pyramidal neurons identified in the same tissue and found that although activity in all cell classes was modulated by both attention and VIP manipulation, their effects were orthogonal. Attention and VIP-SOM disinhibition relied on distinct patterns of changes in activity and reorganization of interactions between inhibitory and excitatory cells. Circuit modeling revealed a precise network architecture consistent with multiplexing strong yet non-interacting modulations in the same neural population.

Modeling apical and basal tree contribution to orientation selectivity in a mouse primary visual cortex layer 2/3 pyramidal cell.

Pyramidal neurons, a mainstay of cortical regions, receive a plethora of inputs from various areas onto their morphologically distinct apical and basal trees. Both trees differentially contribute to the somatic response, defining distinct anatomical and possibly functional sub-units. To elucidate the contribution of each tree to the encoding of visual stimuli at the somatic level, we modeled the response pattern of a mouse L2/3 V1 pyramidal neuron to orientation tuned synaptic input. Towards this goal, we used a morphologically detailed computational model of a single cell that replicates electrophysiological and two-photon imaging data. Our simulations predict a synergistic effect of apical and basal trees on somatic action potential generation: basal tree activity, in the form of either depolarization or dendritic spiking, is necessary for producing somatic activity, despite the fact that most somatic spikes are heavily driven by apical dendritic spikes. This model provides evidence for synergistic computations taking place in the basal and apical trees of the L2/3 V1 neuron along with mechanistic explanations for tree-specific contributions and emphasizes the potential role of predictive and attentional feedback input in these cells.

Neurons in the primary visual cortex of freely moving rats encode both sensory and non-sensory task variables.

Neurons in primary visual cortex (area V1) are strongly driven by both sensory stimuli and non-sensory events. However, although the representation of sensory stimuli has been well characterized, much less is known about the representation of non-sensory events. Here, we characterize the specificity and organization of non-sensory representations in rat V1 during a freely moving visual decision task. We find that single neurons encode diverse combinations of task features simultaneously and across task epochs. Despite heterogeneity at the level of single neuron response patterns, both visual and nonvisual task variables could be reliably decoded from small neural populations (5 to 40 units) throughout a trial. Interestingly, in animals trained to make an auditory decision following passive observation of a visual stimulus, some but not all task features could also be decoded from V1 activity. Our results support the view that even in V1-the earliest stage of the cortical hierarchy-bottom-up sensory information may be combined with top-down non-sensory information in a task-dependent manner.

Normalization in mouse primary visual cortex.

When multiple stimuli appear together in the receptive field of a visual cortical neuron, the response is typically close to the average of that neuron's response to each individual stimulus. The departure from a linear sum of each individual response is referred to as normalization. In mammals, normalization has been best characterized in the visual cortex of macaques and cats. Here we study visually evoked normalization in the visual cortex of awake mice using imaging of calcium indicators in large populations of layer 2/3 (L2/3) V1 excitatory neurons and electrophysiological recordings across layers in V1. Regardless of recording method, mouse visual cortical neurons exhibit normalization to varying degrees. The distributions of normalization strength are similar to those described in cats and macaques, albeit slightly weaker on average.

A power law describes the magnitude of adaptation in neural populations of primary visual cortex.

How do neural populations adapt to the time-varying statistics of sensory input? We used two-photon imaging to measure the activity of neurons in mouse primary visual cortex adapted to different sensory environments, each defined by a distinct probability distribution over a stimulus set. We find that two properties of adaptation capture how the population response to a given stimulus, viewed as a vector, changes across environments. First, the ratio between the response magnitudes is a power law of the ratio between the stimulus probabilities. Second, the response direction to a stimulus is largely invariant. These rules could be used to predict how cortical populations adapt to novel, sensory environments. Finally, we show how the power law enables the cortex to preferentially signal unexpected stimuli and to adjust the metabolic cost of its sensory representation to the entropy of the environment.

Local field potential responses associated with perceptual filling-in at blind spot in macaque primary visual cortex.

To understand the neural mechanisms of perceptual filling-in at the blind spot (BS), we analyzed neural activity in the region representing the visual field corresponding to the BS (BS region) in the primary visual cortex (V1) of the macaque monkey. We inserted a linear array electrode into the BS region or surrounding region and recorded the multiunit activities (MUAs) and local field potential (LFP). We examined the responses of MUAs and LFP to a large visual stimulus that entirely covered the BS (surface stimuli) while the monkey performed a visual fixation task in either the monocular condition without receiving direct retinal input or the binocular condition receiving retinal information. We observed clear MUA responses in the deep layers within the BS region under monocular conditions, confirming previous reports that V1 neurons in the BS region are activated when perceptual filling-in occurs. Current source density analysis using LFP showed that MUA responses were mainly observed in layer 5. Although LFP responses were generally stronger in the binocular condition than in the monocular condition, a notable exception was observed in the BS region. LFP responses in the low-beta band in the superficial layers were stronger in the monocular condition than in the binocular condition. These results suggest that low-beta activity in the superficial layer is related to the occurrence of perceptual filling-in in the BS. The origin of this activity is considered to be feedback signals from the extrastriate areas to the V1.NEW & NOTEWORTHY Two characteristic activities were induced in the blind spot (BS) region in response to the stimulus, causing perceptual filling-in: 1) beta-band LFP responses in the superficial layers and 2) neuronal responses in the deep layers, mainly in layer 5. These data suggest that the feedback signal from the extrastriate areas to the BS region in V1 is involved in perceptual filling-in.

Targeted V1 comodulation supports task-adaptive sensory decisions.

Sensory-guided behavior requires reliable encoding of stimulus information in neural populations, and flexible, task-specific readout. The former has been studied extensively, but the latter remains poorly understood. We introduce a theory for adaptive sensory processing based on functionally-targeted stochastic modulation. We show that responses of neurons in area V1 of monkeys performing a visual discrimination task exhibit low-dimensional, rapidly fluctuating gain modulation, which is stronger in task-informative neurons and can be used to decode from neural activity after few training trials, consistent with observed behavior. In a simulated hierarchical neural network model, such labels are learned quickly and can be used to adapt downstream readout, even after several intervening processing stages. Consistently, we find the modulatory signal estimated in V1 is also present in the activity of simultaneously recorded MT units, and is again strongest in task-informative neurons. These results support the idea that co-modulation facilitates task-adaptive hierarchical information routing.

Behavioral examination of the role of the primary visual cortex in the perceived size representation.

Previous research has shown that neural activity in the primary visual cortex (V1) and V1 surface area may be linked with subjective experience of size illusions. Here, we behaviorally measured the hallway illusion with experimental manipulations as a proxy of V1's influence on size perception. We first tested whether the hallway illusion can persist without further recurrent processing by using backward masking. Next, we examined relations among the hallway illusion magnitude and other perceptual measures that have been suggested to be correlated with V1 surface area. In Experiment 1, the magnitude of the hallway illusion was not affected by the stimulus duration and visual masking when the hallway context was previewed (i.e., complex depth information is already processed). It suggests that V1 activity could support the size illusion to some extent even when recurrent processing between V1 and higher areas is disturbed. In Experiment 2, the hallway illusion magnitude was correlated with the Vernier acuity threshold, but not with physical size discriminability. Our results provide converging evidence with the previous findings in that neural activity in V1 may contribute to size illusions and that V1 surface area is not the sole factor that mediates size perception and visual precision.

Continuous multiplexed population representations of task context in the mouse primary visual cortex.

Effective task execution requires the representation of multiple task-related variables that determine how stimuli lead to correct responses. Even the primary visual cortex (V1) represents other task-related variables such as expectations, choice, and context. However, it is unclear how V1 can flexibly accommodate these variables without interfering with visual representations. We trained mice on a context-switching cross-modal decision task, where performance depends on inferring task context. We found that the context signal that emerged in V1 was behaviorally relevant as it strongly covaried with performance, independent from movement. Importantly, this signal was integrated into V1 representation by multiplexing visual and context signals into orthogonal subspaces. In addition, auditory and choice signals were also multiplexed as these signals were orthogonal to the context representation. Thus, multiplexing allows V1 to integrate visual inputs with other sensory modalities and cognitive variables to avoid interference with the visual representation while ensuring the maintenance of task-relevant variables.