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Parallel visual pathways from the retina to the primary visual cortex (V1) via the lateral geniculate nucleus are common to many mammalian species, including mice, carnivores, and primates. However, it remains unclear which visual features present in both retina and V1 may be inherited from parallel pathways versus extracted by V1 circuits in the mouse. Here, using calcium imaging and rabies circuit tracing, we explore the relationships between tuning of layer 4 (L4) V1 neurons and their retinal ganglion cell (RGC) inputs. We find that subpopulations of L4 V1 neurons differ in their tuning for direction, orientation, spatial frequency, temporal frequency, and speed. Furthermore, we find that direction-tuned L4 V1 neurons receive input from direction-selective RGCs, whereas orientation-tuned L4 V1 neurons receive input from orientation-selective RGCs. These results suggest that direction and orientation tuning of V1 neurons may be partly inherited from parallel pathways originating in the retina., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Visual perception is formed over time through the formation process and visual pathway. Exercise improves visual perception, but it is unclear whether exercise modulates nonspecifically or specifically the formation process and pathway of visual perception. Healthy young men performed the visual detection task in a backward masking paradigm before and during cycling exercise at a mild intensity or rest (control). The task presented gratings of a circular patch (target) and annulus (mask) arranged concentrically as a visual stimulus and asked if the presence and striped pattern (feature) of the target were detected. The relationship between the orientations of the gratings of the target and the mask included iso-orientation and orthogonal orientation to investigate the orientation selectivity of the masking effect. The masking effect was evaluated by perceptual suppressive index (PSI). Exercise improved feature detection (∆PSI; Exercise: -20.6%, Control: 1.7%) but not presence detection (∆PSI; Exercise: 8.9%, Control: 29.6%) compared to the control condition, and the improving effect resulted from the attenuation of the non-orientation-selective (∆PSI; Exercise: -29.0%, Control: 16.8%) but not orientation-selective masking effect (∆PSI; Exercise: -3.1%, Control: 11.7%). These results suggest that exercise affects the formation process of the perceptual feature of the target stimulus by suppressively modulating the neural networks responsible for the non-orientation-selective surround interaction in the subcortical visual pathways, whose effects are inherited by the cortical visual pathways necessary for perceptual image formation. In conclusion, our findings suggest that acute exercise improves visual perception transiently through the modulation of a specific formation process of visual processing., (© 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Experience dependent plasticity in the visual cortex is a key paradigm for the study of mechanisms underpinning learning and memory. Despite this, studies involving manipulating visual experience have largely been limited to the primary visual cortex, V1, across various species. Here we investigated the effects of monocular deprivation (MD) on the ocular dominance (OD) and orientation selectivity of neurons in four visual cortical areas in the mouse: the binocular zone of V1 (V1b), the putative "ventral stream" area LM and the putative "dorsal stream" areas AL and PM. We employed two-photon calcium imaging to record neuronal responses in young adult mice before MD, immediately after MD, and following binocular recovery. OD shifts following MD were greatest in LM and smallest in AL and PM; in LM and AL, these shifts were mediated primarily through a reduction of deprived-eye responses, in V1b and LM through an increase in response through the non-deprived eye. The OD index recovered to pre-MD levels within 2 weeks in V1 only. MD caused a reduction in orientation selectivity of deprived-eye responses in V1b and LM only. Our results suggest that changes in OD in higher visual areas are not uniformly inherited from V1., (© The Author(s) 2023. Published by Oxford University Press.)

Over the past few years, the various areas that surround the primary visual cortex (V1) in the mouse have been associated with many functions, ranging from higher order visual processing to decision-making. Recently, some studies have shown that higher order visual areas influence the activity of the primary visual cortex, refining its processing capabilities. Here, we studied how in vivo optogenetic inactivation of two higher order visual areas with different functional properties affects responses evoked by moving bars in the primary visual cortex. In contrast with the prevailing view, our results demonstrate that distinct higher order visual areas similarly modulate early visual processing. In particular, these areas enhance stimulus responsiveness in the primary visual cortex, by more strongly amplifying weaker compared with stronger sensory-evoked responses (for instance specifically amplifying responses to stimuli not moving along the direction preferred by individual neurons) and by facilitating responses to stimuli entering the receptive field of single neurons. Such enhancement, however, comes at the expense of orientation and direction selectivity, which increased when the selected higher order visual areas were inactivated. Thus, feedback from higher order visual areas selectively amplifies weak sensory-evoked V1 responses, which may enable more robust processing of visual stimuli., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Most neurons in the primary visual cortex (V1) of mammals show sharp orientation selectivity and band-pass spatial frequency tuning. Here, we examine whether sharpening of the broad tuning that exists subcortically, namely in the retina and the lateral geniculate nucleus (LGN), underlie the sharper tuning seen for both the above features in tree shrew V1. Since the transition from poor feature selectivity to sharp tuning occurs entirely within V1 in tree shrews, we examined the orientation selectivity and spatial frequency tuning of neurons within individual electrode penetrations. We found that most layer 4 and layer 2/3 neurons in the same cortical column preferred the same stimulus orientation. However, a subset of layer 3c neurons close to the layer 4 border preferred near orthogonal orientations, suggesting that layer 2/3 neurons may inherit the orientation preferences of their layer 4 input neurons and also receive cross-orientation inhibition from layer 3c neurons. We also found that layer 4 neurons showed sharper orientation selectivity at higher spatial frequencies, suggesting that attenuation of low spatial frequency responses by spatially broad inhibition acting on layer 4 inputs to layer 2/3 neurons can enhance both orientation and spatial frequency selectivities. However, in a proportion of layer 2/3 neurons, the sharper tuning of layer 2/3 neurons appeared to arise also or even mainly from inhibition specific to high spatial frequencies acting on the layer 4 inputs to layer 2/3. Overall, our results are consistent with the suggestion that in tree shrews, sharp feature selectivity in layer 2/3 can be established by intracortical mechanisms that sharpen biases observed in layer 4, which are in turn inherited presumably from thalamic afferents., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Selectivity for many basic properties of visual stimuli, such as orientation, is thought to be organized at the scale of cortical columns, making it difficult or impossible to measure directly with noninvasive human neuroscience measurement. However, computational analyses of neuroimaging data have shown that selectivity for orientation can be recovered by considering the pattern of response across a region of cortex. This suggests that computational analyses can reveal representation encoded at a finer spatial scale than is implied by the spatial resolution limits of measurement techniques. This potentially opens up the possibility to study a much wider range of neural phenomena that are otherwise inaccessible through noninvasive measurement. However, as we review in this article, a large body of evidence suggests an alternative hypothesis to this superresolution account: that orientation information is available at the spatial scale of cortical maps and thus easily measurable at the spatial resolution of standard techniques. In fact, a population model shows that this orientation information need not even come from single-unit selectivity for orientation tuning, but instead can result from population selectivity for spatial frequency. Thus, a categorical error of interpretation can result whereby orientation selectivity can be confused with spatial frequency selectivity. This is similarly problematic for the interpretation of results from numerous studies of more complex representations and cognitive functions that have built upon the computational techniques used to reveal stimulus orientation. We suggest in this review that these interpretational ambiguities can be avoided by treating computational analyses as models of the neural processes that give rise to measurement. Building upon the modeling tradition in vision science using considerations of whether population models meet a set of core criteria is important for creating the foundation for a cumulative and replicable approach to making valid inferences from human neuroscience measurements.

The mouse, as a model organism to study the brain, gives us unprecedented experimental access to the mammalian cerebral cortex. By determining the cortex's cellular composition, revealing the interaction between its different components, and systematically perturbing these components, we are obtaining mechanistic insight into some of the most basic properties of cortical function. In this review, we describe recent advances in our understanding of how circuits of cortical neurons implement computations, as revealed by the study of mouse primary visual cortex. Further, we discuss how studying the mouse has broadened our understanding of the range of computations performed by visual cortex. Finally, we address how future approaches will fulfill the promise of the mouse in elucidating fundamental operations of cortex.

Motion streaks are smeared representation of fast-moving objects due to temporal integration. Here, we test for motion streak signals in mice with two-photon calcium imaging. For small dots moving at low speeds, neurons in primary visual cortex (V1) encode the component motion, with preferred direction along the axis perpendicular to their preferred orientation. At high speeds, V1 neurons prefer the direction along the axis parallel to their preferred orientation, as expected for encoding motion streaks. Whereas some V1 neurons (∼20%) display a switch of preferred motion axis with increasing speed, others (>40%) respond specifically to high speeds at the parallel axis. Motion streak neurons are also seen in higher visual lateromedial (LM), anterolateral (AL), and rostrolateral (RL) areas, but with higher transition speeds, and many still prefer the perpendicular axis even with fast motion. Our results thus indicate that diverse motion encoding exists in mouse visual cortex, with intriguing differences among visual areas., Competing Interests: Declaration of Interests The authors declare no competing interests., (Published by Elsevier Inc.)

The potential for neuronal representations of external stimuli to be modified by previous experience is critical for efficient sensory processing and improved behavioral outcomes. To investigate how repeated exposure to a visual stimulus affects its representation in mouse primary visual cortex (V1), we performed two-photon calcium imaging of layer 2/3 neurons and assessed responses before, during, and after the presentation of a repetitive stimulus over 5 consecutive days. We found a stimulus-specific enhancement of the neuronal representation of the repetitively presented stimulus when it was associated with a reward. This was observed both after mice actively learned a rewarded task and when the reward was randomly received. Stimulus-specific enhanced representation resulted both from neurons gaining selectivity and from increased response reliability in previously selective neurons. In the absence of reward, there was either no change in stimulus representation or a decreased representation when the stimulus was viewed at a fixed temporal frequency. Pairing a second stimulus with a reward led to a similar enhanced representation and increased discriminability between the equally rewarded stimuli. Single-neuron responses showed that separate subpopulations discriminated between the two rewarded stimuli depending on whether the stimuli were displayed in a virtual environment or viewed on a single screen. We suggest that reward-associated responses enable the generalization of enhanced stimulus representation across these V1 subpopulations. We propose that this dynamic regulation of visual processing based on the behavioral relevance of sensory input ultimately enhances and stabilizes the representation of task-relevant features while suppressing responses to non-relevant stimuli., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

In mouse visual cortex, right after eye opening binocular cells have different preferred orientations for input from the two eyes. With normal visual experience during a critical period, these preferred orientations evolve and eventually become well matched. To gain insight into the matching process, we developed a computational model of a cortical cell receiving orientation selective inputs via plastic synapses. The model captures the experimentally observed matching of the preferred orientations, the dependence of matching on ocular dominance of the cell, and the relationship between the degree of matching and the resulting monocular orientation selectivity. Moreover, our model puts forward testable predictions: 1 ) The matching speed increases with initial ocular dominance. 2 ) While the matching improves more slowly for cells that are more orientation selective, the selectivity increases faster for better matched cells during the matching process. This suggests that matching drives orientation selectivity but not vice versa. 3 ) There are two main routes to matching: the preferred orientations either drift toward each other or one of the orientations switches suddenly. The latter occurs for cells with large initial mismatch and can render the cells monocular. We expect that these results provide insight more generally into the development of neuronal systems that integrate inputs from multiple sources, including different sensory modalities. NEW & NOTEWORTHY Animals gather information through multiple modalities (vision, audition, touch, etc.). These information streams have to be merged coherently to provide a meaningful representation of the world. Thus, for neurons in visual cortex V1, the orientation selectivities for inputs from the two eyes have to match to enable binocular vision. We analyze the postnatal process underlying this matching using computational modeling. It captures recent experimental results and reveals interdependence between matching, ocular dominance, and orientation selectivity.

Spike (action potential) responses of most primary visual cortical cells in the macaque are sharply tuned for the orientation of a line or an edge, and neurons preferring similar orientations are clustered together in cortical columns. The preferred stimulus orientation of these columns span the full range of orientations, as observed in recordings of spikes and in classical optical imaging of intrinsic signals. However, when we imaged the putative thalamic input to striate cortical cells that can be seen in imaging of intrinsic signals when they are analyzed on a larger spatial scale, we found that the orientation domain map of the primary visual cortex did not show the same diversity of orientations. This map was dominated by just the one orientation that is most commonly preferred by neurons in the retina and the lateral geniculate nucleus. This supports cortical feature selectivity and columnar architecture being built upon feed-forward signals transmitted from the thalamus in a very limited number of broadly tuned input channels., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Feedback regulation from the higher association areas is thought to control the primary sensory cortex, contribute to the cortical processing of sensory information, and work for higher cognitive functions such as multimodal integration and attentional control. However, little is known about the underlying neural mechanisms. Here, we show that the posterior parietal cortex (PPC) persistently inhibits the activity of the primary visual cortex (V1) in mice. Activation of the PPC causes the suppression of visual responses in V1 and induces the short-term depression, which is specific to visual stimuli. In contrast, pharmacological inactivation of the PPC or disconnection of cortical pathways from the PPC to V1 results in an effect of transient enhancement of visual responses in V1. Two-photon calcium imaging demonstrated that the cortical disconnection caused V1 excitatory neurons an enhancement of visual responses and a reduction of orientation selectivity index (OSI). These results show that the PPC regulates the response properties of V1 excitatory neurons. Our findings reveal one of the functions of the PPC, which may contribute to higher brain functions in mice., (© 2019 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Multimodal sensory integration facilitates the generation of a unified and coherent perception of the environment. It is now well established that unimodal sensory perceptions, such as vision, are improved in multisensory contexts. Whereas multimodal integration is primarily performed by dedicated multisensory brain regions such as the association cortices or the superior colliculus, recent studies have shown that multisensory interactions also occur in primary sensory cortices. In particular, sounds were shown to modulate the responses of neurons located in layers 2/3 (L2/3) of the mouse primary visual cortex (V1). Yet, the net effect of sound modulation at the V1 population level remained unclear. In the present study, we performed two-photon calcium imaging in awake mice to compare the representation of the orientation and the direction of drifting gratings by V1 L2/3 neurons in unimodal (visual only) or multimodal (audiovisual) conditions. We found that sound modulation depended on the tuning properties (orientation and direction selectivity) and response amplitudes of V1 L2/3 neurons. Sounds potentiated the responses of neurons that were highly tuned to the cue's orientation and direction but weakly active in the unimodal context, following the principle of inverse effectiveness of multimodal integration. Moreover, sound suppressed the responses of neurons untuned for the orientation and/or the direction of the visual cue. Altogether, sound modulation improved the representation of the orientation and direction of the visual stimulus in V1 L2/3. Namely, visual stimuli presented with auditory stimuli recruited a neuronal population better tuned to the visual stimulus orientation and direction than when presented alone. NEW & NOTEWORTHY The primary visual cortex (V1) receives direct inputs from the primary auditory cortex. Yet, the impact of sounds on visual processing in V1 remains controverted. We show that the modulation by pure tones of V1 visual responses depends on the orientation selectivity, direction selectivity, and response amplitudes of V1 neurons. Hence, audiovisual stimuli recruit a population of V1 neurons better tuned to the orientation and direction of the visual stimulus than unimodal visual stimuli.

This in vivo study shows that both intrinsic and sensory-evoked synaptic properties of layer 2/3 neurons in mouse visual cortex are modified by ongoing visual input. Following visual deprivation, intrinsic properties are significantly altered, although orientation selectivity across the population remains unchanged. We, therefore, suggest that cortical cells adjust their intrinsic excitability in an activity-dependent manner to compensate for changes in synaptic drive and maintain sensory network function., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

In the cortex, demarcated unimodal sensory regions often respond to unforeseen sensory stimuli and exhibit plasticity. The goal of the current investigation was to test evoked responses of primary visual cortex (V1) neurons when an adapting auditory stimulus is applied in isolation. Using extracellular recordings in anesthetized cats, we demonstrate that, unlike the prevailing observation of only slight modulations in the firing rates of the neurons, sound imposition in isolation entirely shifted the peaks of orientation tuning curves of neurons in both supra- and infragranular layers of V1. Our results suggest that neurons specific to either layer dynamically integrate features of sound and modify the organization of the orientation map of V1. Intriguingly, these experiments present novel findings that the mere presentation of a prolonged auditory stimulus may drastically recalibrate the tuning properties of the visual neurons and highlight the phenomenal neuroplasticity of V1 neurons., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)

To combat retinal degeneration, healthy fetal retinal sheets have been successfully transplanted into both rodent models and humans, with synaptic connectivity between transplant and degenerated host retina having been confirmed. In rodent studies, transplants have been shown to restore responses to flashes of light in a region of the superior colliculus corresponding to the location of the transplant in the host retina. To determine the quality and detail of visual information provided by the transplant, visual responsivity was studied here at the level of visual cortex where higher visual perception is processed. For our model, we used the transgenic Rho-S334ter line-3 rat (both sexes), which loses photoreceptors at an early age and is effectively blind at postnatal day 30. These rats received fetal retinal sheet transplants in one eye between 24 and 40 d of age. Three to 10 months following surgery, visually responsive neurons were found in regions of primary visual cortex matching the transplanted region of the retina that were as highly selective as normal rat to stimulus orientation, size, contrast, and spatial and temporal frequencies. Conversely, we found that selective response properties were largely absent in nontransplanted line-3 rats. Our data show that fetal retinal sheet transplants can result in remarkably normal visual function in visual cortex of rats with a degenerated host retina and represents a critical step toward developing an effective remedy for the visually impaired human population. SIGNIFICANCE STATEMENT Age-related macular degeneration and retinitis pigmentosa lead to profound vision loss in millions of people worldwide. Many patients lose both retinal pigment epithelium and photoreceptors. Hence, there is a great demand for the development of efficient techniques that allow for long-term vision restoration. In this study, we transplanted dissected fetal retinal sheets, which can differentiate into photoreceptors and integrate with the host retina of rats with severe retinal degeneration. Remarkably, we show that transplants generated visual responses in cortex similar in quality to normal rats. Furthermore, transplants preserved connectivity within visual cortex and the retinal relay from the lateral geniculate nucleus to visual cortex, supporting their potential application in curing vision loss associated with retinal degeneration., (Copyright © 2018 the authors 0270-6474/18/3810709-16$15.00/0.)

Recent experiments have shown that mouse primary visual cortex (V1) is very different from that of cat or monkey, including response properties-one of which is that contrast invariance in the orientation selectivity (OS) of the neurons' firing rates is replaced in mouse with contrast-dependent sharpening (broadening) of OS in excitatory (inhibitory) neurons. These differences indicate a different circuit design for mouse V1 than that of cat or monkey. Here we develop a large-scale computational model of an effective input layer of mouse V1. Constrained by experiment data, the model successfully reproduces experimentally observed response properties-for example, distributions of firing rates, orientation tuning widths, and response modulations of simple and complex neurons, including the contrast dependence of orientation tuning curves. Analysis of the model shows that strong feedback inhibition and strong orientation-preferential cortical excitation to the excitatory population are the predominant mechanisms underlying the contrast-sharpening of OS in excitatory neurons, while the contrast-broadening of OS in inhibitory neurons results from a strong but nonpreferential cortical excitation to these inhibitory neurons, with the resulting contrast-broadened inhibition producing a secondary enhancement on the contrast-sharpened OS of excitatory neurons. Finally, based on these mechanisms, we show that adjusting the detailed balances between the predominant mechanisms can lead to contrast invariance-providing insights for future studies on contrast dependence (invariance)., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

The connectivity principles underlying the emergence of orientation selectivity in primary visual cortex (V1) of mammals lacking an orientation map (such as rodents and lagomorphs) are poorly understood. We present a computational model in which random connectivity gives rise to orientation selectivity that matches experimental observations. The model predicts that mouse V1 neurons should exhibit intricate receptive fields in the two-dimensional frequency domain, causing a shift in orientation preferences with spatial frequency. We find evidence for these features in mouse V1 using calcium imaging and intracellular whole-cell recordings., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

In the primary visual cortex (V1) of many mammalian species, neurons are spatially organized according to their preferred orientation into a highly ordered map. However, whether and how the various presynaptic inputs to V1 neurons are organized relative to the neuronal orientation map remain unclear. To address this issue, we constructed genetically encoded calcium indicators targeting axon boutons in two colors and used them to map the organization of axon boutons of V1 intrinsic and V2-V1 feedback projections in tree shrews. Both connections are spatially organized into maps according to the preferred orientations of axon boutons. Dual-color calcium imaging showed that V1 intrinsic inputs are precisely aligned to the orientation map of V1 cell bodies, while the V2-V1 feedback projections are aligned to the V1 map with less accuracy. Nonselective integration of intrinsic presynaptic inputs around the dendritic tree is sufficient to reproduce cell body orientation preference. These results indicate that a precisely aligned map of intrinsic inputs could reinforce the neuronal map in V1, a principle that may be prevalent for brain areas with function maps., Competing Interests: The authors declare no conflict of interest.

Orientation selectivity is an important feature of visual cortical neurons. Optical imaging of the visual cortex allows for the generation of maps of orientation selectivity that reflect the activity of large populations of neurons. To estimate the statistical significance of effects of experimental manipulations, evaluation of the stability of cortical maps over time is required. Here, we performed optical imaging recordings of the visual cortex of anesthetized adult cats. Monocular stimulation with moving clockwise square-wave gratings that continuously changed orientation and direction was used as the mapping stimulus. Recordings were repeated at various time intervals, from 15 min to 16 h. Quantification of map stability was performed on a pixel-by-pixel basis using several techniques. Map reproducibility showed clear dynamics over time. The highest degree of stability was seen in maps recorded 15-45 min apart. Averaging across all time intervals and all stimulus orientations revealed a mean shift of 2.2 ± 0.1°. There was a significant tendency for larger shifts to occur at longer time intervals. Shifts between 2.8° (mean ± 2SD) and 5° were observed more frequently at oblique orientations, while shifts greater than 5° appeared more frequently at cardinal orientations. Shifts greater than 5° occurred rarely overall (5.4% of cases) and never exceeded 11°. Shifts of 10-10.6° (0.7%) were seen occasionally at time intervals of more than 4 h. Our findings should be considered when evaluating the potential effect of experimental manipulations on orientation selectivity mapping studies., (Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.)

Bisphenol A (BPA), a common environmental xenoestrogen, has been implicated in physiological and behavioral impairment, but the neuronal basis remains elusive. Although various synaptic mechanisms have been shown to mediate BPA-induced brain deficits, there are almost no reports addressing its underlying physiological mechanisms at the individual neuron level, particularly in the primary visual system. In the present study, using multiple-channel recording technique, we recorded the responses of single neurons in the primary visual system of cats to various direction stimuli both before and after BPA exposure. The results showed that the orientation selectivity of neurons in the primary visual cortex (area 17, A17) was obviously decreased after 2 h of intravenous BPA administration (0.2 mg/kg). Moreover, there were worse performances of information transmission of A17 neurons, presenting markedly decreased signal-to-noise ratio (SNR). To some extent, these functional decreases were attributable to the altered information inputs from lateral geniculate nucleus (LGN), which showed an increased spontaneous activity. Additionally, local injection of BPA (3.3 μg/ml) in A17 resulted in an obvious increase in orientation selectivity and a decrease in neuronal activity, involving enhanced activity of fast-spiking inhibitory interneurons. In conclusion, our results first demonstrate that acute BPA exposure can restrict the visual perception of cats, mainly depending on the alteration of the LGN projection, not the intercortical interaction. Importantly, BPA-induced-brain deficits might not only be confined to the cortical level but also occur as early as at the subcortical level.

Binocular mechanisms for visual processing are thought to enhance spatial acuity by combining matched input from the two eyes. Studies in the primary visual cortex of carnivores and primates have confirmed that eye-specific neuronal response properties are largely matched. In recent years, the mouse has emerged as a prominent model for binocular visual processing, yet little is known about the spatial frequency tuning of binocular responses in mouse visual cortex. Using calcium imaging in awake mice of both sexes, we show that the spatial frequency preference of cortical responses to the contralateral eye is ∼35% higher than responses to the ipsilateral eye. Furthermore, we find that neurons in binocular visual cortex that respond only to the contralateral eye are tuned to higher spatial frequencies. Binocular neurons that are well matched in spatial frequency preference are also matched in orientation preference. In contrast, we observe that binocularly mismatched cells are more mismatched in orientation tuning. Furthermore, we find that contralateral responses are more direction-selective than ipsilateral responses and are strongly biased to the cardinal directions. The contralateral bias of high spatial frequency tuning was found in both awake and anesthetized recordings. The distinct properties of contralateral cortical responses may reflect the functional segregation of direction-selective, high spatial frequency-preferring neurons in earlier stages of the central visual pathway. Moreover, these results suggest that the development of binocularity and visual acuity may engage distinct circuits in the mouse visual system. SIGNIFICANCE STATEMENT Seeing through two eyes is thought to improve visual acuity by enhancing sensitivity to fine edges. Using calcium imaging of cellular responses in awake mice, we find surprising asymmetries in the spatial processing of eye-specific visual input in binocular primary visual cortex. The contralateral visual pathway is tuned to higher spatial frequencies than the ipsilateral pathway. At the highest spatial frequencies, the contralateral pathway strongly prefers to respond to visual stimuli along the cardinal (horizontal and vertical) axes. These results suggest that monocular, and not binocular, mechanisms set the limit of spatial acuity in mice. Furthermore, they suggest that the development of visual acuity and binocularity in mice involves different circuits., (Copyright © 2017 the authors 0270-6474/17/3710125-14$15.00/0.)

Neural circuits are shaped by experience during critical periods of development. Sensory deprivation during these periods permanently compromises an organism's ability to perceive the outside world. In the mouse visual system, normal visual experience during a critical period in early life drives the matching of individual cortical neurons' orientation preferences through the two eyes, likely a key step in the development of binocular vision. Here, in mice of both sexes, we show that the binocular matching process is completely blocked by monocular deprivation spanning the entire critical period. We then show that 3 weeks of environmental enrichment (EE), a paradigm of enhanced sensory, motor, and cognitive stimulation, is sufficient to rescue binocular matching to the level seen in unmanipulated mice. In contrast, 6 weeks of conventional housing only resulted in a partial rescue. Finally, we use two-photon calcium imaging to track the matching process chronically in individual cells during EE-induced rescue. We find that for cells that are clearly dominated by one of the two eyes, the input representing the weaker eye changes its orientation preference to align with that of the dominant eye. These results thus reveal ocular dominance as a key driver of the binocular matching process, and suggest a model whereby the dominant input instructs the development of the weaker input. Such a mechanism may operate in the development of other systems that need to integrate inputs from multiple sources to generate normal neuronal functions. SIGNIFICANCE STATEMENT Critical periods are developmental windows of opportunity that ensure the proper wiring of neural circuits, as well as windows of vulnerability when abnormal experience could cause lasting damage to the developing brain. In the visual system, critical period plasticity drives the establishment of binocularly matched orientation preferences in cortical neurons. Here, we show that binocular matching is completely blocked by monocular deprivation during the critical period. Moreover, environmental enrichment can fully rescue the disrupted matching, whereas conventional housing of twice the duration results in a partial rescue. We then use two-photon calcium imaging to track individual cells chronically during the EE-induced recovery, and reveal important insights into how appropriate function can be restored to the nervous system after the critical period., (Copyright © 2017 the authors 0270-6474/17/375822-12$15.00/0.)

The simple cells of the visual cortex respond over a narrow range of stimulus orientations, and this tuning is invariant to the contrast at which the stimulus is presented. The inputs to a single cell derive from a population of thalamic cells that provide a bell-shaped tuning width and offset that increases with stimulus contrast. Synaptic depression, noise and inhibition have been proposed as feedforward mechanisms to explain why these increases do not appear in simple cells. The extent to which these three mechanisms contribute to contrast-invariant orientation tuning is unknown. Consequently, the aim was to test the hypothesis that these mechanisms do not contribute equally. Unlike previous studies, all mechanisms were examined using the same network model based on Banitt et al. (2007). The results showed that thalamocortical synaptic noise was essential and sufficient to widen tuning widths at low contrasts to that of higher contrasts but could not counteract the offset at higher contrasts. Thalamocortical synaptic depression could only be used to counteract a small fraction of the offset otherwise the relationship between contrast and response rate was disrupted. Only broadly tuned simple and complex cell inhibition could counteract the remaining offset for all stimulus contrasts but complex cell inhibition reduced the gain of the response. These results suggest unequal contributions of these feedforward mechanisms with thalamic synaptic noise widening tuning widths for low contrasts, synaptic depression counteracting a small component of the offset and synaptic inhibition completely removing the remaining offset to produce contrast-invariant orientation tuning., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)

Functional circuits in the visual cortex require the coordinated activity of excitatory and inhibitory neurons. Molecular genetic approaches in the mouse have led to the "local non-specific pooling principle" of inhibitory connectivity, in which inhibitory neurons are untuned for stimulus features due to the random pooling of local inputs. However, it remains unclear whether this principle generalizes to species with a columnar organization of feature selectivity such as carnivores, primates, and humans. Here we use virally mediated GABAergic-specific GCaMP6f expression to demonstrate that inhibitory neurons in ferret visual cortex respond robustly and selectively to oriented stimuli. We find that the tuning of inhibitory neurons is inconsistent with the local non-specific pooling of excitatory inputs and that inhibitory neurons exhibit orientation-specific noise correlations with local and distant excitatory neurons. These findings challenge the generality of the non-specific pooling principle for inhibitory neurons, suggesting different rules for functional excitatory-inhibitory interactions in non-murine species., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Cerebral cortex contains various types of GABAergic neurons exerting local inhibition. Although the number of GABAergic inhibitory neurons is much smaller than glutamatergic excitatory neurons, they show greater diversity in their morphological and physiological properties. Genetic markers for distinct sub-classes of GABAergic neurons have been identified, and technical advances achieved in the past few decades have brought about a demonstration of a unique function of each sub-class of GABAergic neurons in the cortex. In particular, visual processing in the cortex requires inhibitory function of various GABAergic neurons. Here, we summarize current understandings on the function of inhibitory neurons in the cortex, especially focusing on their roles in visual processing., (Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.)

Mammalian neocortical circuits are functionally organized such that the selectivity of individual neurons systematically shifts across the cortical surface, forming a continuous map. Maps of the sensory space exist in cortex, such as retinotopic maps in the visual system or tonotopic maps in the auditory system, but other functional response properties also may be similarly organized. For example, many carnivores and primates possess a map for orientation selectivity in primary visual cortex (V1), whereas mice, rabbits, and the gray squirrel lack orientation maps. In this report we show that a carnivorous rodent with predatory behaviors, the grasshopper mouse ( Onychomys arenicola) , lacks a canonical columnar organization of orientation preference in V1; however, neighboring neurons within 50 μm exhibit related tuning preference. Using a combination of two-photon microscopy and extracellular electrophysiology, we demonstrate that the functional organization of visual cortical neurons in the grasshopper mouse is largely the same as in the C57/BL6 laboratory mouse. We also find similarity in the selectivity for stimulus orientation, direction, and spatial frequency. Our results suggest that the properties of V1 neurons across rodent species are largely conserved. NEW & NOTEWORTHY Carnivores and primates possess a map for orientation selectivity in primary visual cortex (V1), whereas rodents and lagomorphs lack this organization. We examine, for the first time, V1 of a wild carnivorous rodent with predatory behaviors, the grasshopper mouse ( Onychomys arenicola ). We demonstrate the cellular organization of V1 in the grasshopper mouse is largely the same as the C57/BL6 laboratory mouse, suggesting that V1 neuron properties across rodent species are largely conserved., (Copyright © 2017 the American Physiological Society.)

The maturation of cortical parvalbumin-positive (PV) interneurons depends on the interaction of innate and experience-dependent factors. Dark-rearing experiments suggest that visual experience determines when broad orientation selectivity emerges in visual cortical PV interneurons. Here, using neural transplantation and in vivo calcium imaging of mouse visual cortex, we investigated whether innate mechanisms contribute to the maturation of orientation selectivity in PV interneurons. First, we confirmed earlier findings showing that broad orientation selectivity emerges in PV interneurons by 2 weeks after vision onset, ∼35 d after these cells are born. Next, we assessed the functional development of transplanted PV (tPV) interneurons. Surprisingly, 25 d after transplantation (DAT) and >2 weeks after vision onset, we found that tPV interneurons have not developed broad orientation selectivity. By 35 DAT, however, broad orientation selectivity emerges in tPV interneurons. Transplantation does not alter orientation selectivity in host interneurons, suggesting that the maturation of tPV interneurons occurs independently from their endogenous counterparts. Together, these results challenge the notion that the onset of vision solely determines when PV interneurons become broadly tuned. Our results reveal that an innate cortical mechanism contributes to the emergence of broad orientation selectivity in PV interneurons., Significance Statement: Early visual experience and innate developmental programs interact to shape cortical circuits. Visual-deprivation experiments have suggested that the onset of visual experience determines when interneurons mature in the visual cortex. Here we used neuronal transplantation and cellular imaging of visual responses to investigate the maturation of parvalbumin-positive (PV) interneurons. Our results suggest that the emergence of broad orientation selectivity in PV interneurons is innately timed., (Copyright © 2017 the authors 0270-6474/17/370820-10$15.00/0.)

Visual cortical neurons are tuned to similar orientations through the two eyes. The binocularly-matched orientation preference is established during a critical period in early life, but the underlying circuit mechanisms remain unknown. Here, we optogenetically isolated the thalamocortical and intracortical excitatory inputs to individual layer 4 neurons and studied their binocular matching. In adult mice, the thalamic and cortical inputs representing the same eyes are similarly tuned and both are matched binocularly. In mice before the critical period, the thalamic input is already slightly matched, but the weak matching is not manifested due to random connections in the cortex, especially those serving the ipsilateral eye. Binocular matching is thus mediated by orientation-specific changes in intracortical connections and further improvement of thalamic matching. Together, our results suggest that the feed-forward thalamic input may play a key role in initiating and guiding the functional refinement of cortical circuits in critical period development., Competing Interests: The authors declare that no competing interests exist.

A new computational model of the primary visual cortex (V1) of the macaque monkey was constructed to reconcile the visual functions of V1 with anatomical data on its LGN input, the extreme sparseness of which presented serious challenges to theoretically sound explanations of cortical function. We demonstrate that, even with such sparse input, it is possible to produce robust orientation selectivity, as well as continuity in the orientation map. We went beyond that to find plausible dynamic regimes of our new model that emulate simultaneously experimental data for a wide range of V1 phenomena, beginning with orientation selectivity but also including diversity in neuronal responses, bimodal distributions of the modulation ratio (the simple/complex classification), and dynamic signatures, such as gamma-band oscillations. Intracortical interactions play a major role in all aspects of the visual functions of the model., Significance Statement: We present the first realistic model that has captured the sparseness of magnocellular LGN inputs to the macaque primary visual cortex and successfully derived orientation selectivity from them. Three implications are (1) even in input layers to the visual cortex, the system is less feedforward and more dominated by intracortical signals than previously thought, (2) interactions among cortical neurons in local populations produce dynamics not explained by single neurons, and (3) such dynamics are important for function. Our model also shows that a comprehensive picture is necessary to explain function, because different visual properties are related. This study points to the need for paradigm shifts in neuroscience modeling: greater emphasis on population dynamics and, where possible, a move toward data-driven, comprehensive models., (Copyright © 2016 the authors 0270-6474/16/3612368-17$15.00/0.)

In spite of the fact that the functional organization of primary visual cortices (V1) differs across species, the dynamic of orientation selectivity is highly structured within neuronal populations. In fact, neurons functionally connect each other in an organized Hebbian process, wherein their wiring and firing are intimately related. Moreover, neuronal ensembles have been suggested to be strongly implicated in sensory processing. Within these ensembles, neurons may be sharply or broadly tuned in relation to the stimulus. Therefore, it is important to determine the relationship between the response selectivity of neurons and their functional connectivity pattern across species. In the present investigation, we sought to compare the stimulus-evoked functional connectivity between the broadly tuned and the sharply tuned neurons in two species exhibiting different cortical organization for orientation selectivity: cats (columnar-organized) and mice (salt-and-pepper organization). In addition, we examined the distribution of connectivity weights within cell-assemblies in the visual cortex during visual adaptation. First, we report that the sharply tuned neurons exhibited higher synchrony index than the broadly tuned cells in the cat visual cortex. On the contrary, in mice, the broadly tuned cells displayed higher connectivity index. Second, a significant correlation was found between the connectivity strength and the difference of preferred orientations of neurons for both species. Finally, we observed a systematic adjustment of the connectivity weights within neuronal ensembles in mouse primary visual cortex similarly to the cat V1., (Copyright © 2016 IBRO. All rights reserved.)

The mechanisms underlying the emergence of orientation selectivity in the visual cortex have been, and continue to be, the subjects of intense scrutiny. Orientation selectivity reflects a dramatic change in the representation of the visual world: Whereas afferent thalamic neurons are generally orientation insensitive, neurons in the primary visual cortex (V1) are extremely sensitive to stimulus orientation. This profound change in the receptive field structure along the visual pathway has positioned V1 as a model system for studying the circuitry that underlies neural computations across the neocortex. The neocortex is characterized anatomically by the relative uniformity of its circuitry despite its role in processing distinct signals from region to region. A combination of physiological, anatomical, and theoretical studies has shed some light on the circuitry components necessary for generating orientation selectivity in V1. This targeted effort has led to critical insights, as well as controversies, concerning how neural circuits in the neocortex perform computations.

The response properties of neurons to sensory stimuli have been used to identify their receptive fields and to functionally map sensory systems. In primary visual cortex, most neurons are selective to a particular orientation and spatial frequency of the visual stimulus. Using two-photon calcium imaging of neuronal populations from the primary visual cortex of mice, we have characterized the response properties of neurons to various orientations and spatial frequencies. Surprisingly, we found that the orientation selectivity of neurons actually depends on the spatial frequency of the stimulus. This dependence can be easily explained if one assumed spatially asymmetric Gabor-type receptive fields. We propose that receptive fields of neurons in layer 2/3 of visual cortex are indeed spatially asymmetric, and that this asymmetry could be used effectively by the visual system to encode natural scenes.

The computation of texture and shape involves integration of features of various orientations. Orientation networks within V1 tend to involve cells which share similar orientation selectivity. However, emergent properties in V2 require the integration of multiple orientations. We now show that, unlike interactions within V1, V1-V2 orientation interactions are much less synchronized and are not necessarily orientation dependent. We find V1-V2 orientation networks are of two types: a more tightly synchronized, orientation-preserving network and a less synchronized orientation-diverse network. We suggest that such diversity of V1-V2 interactions underlies the spatial and functional integration required for computation of higher order contour and shape in V2., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In this study, we investigated orientation selectivity in cat primary visual cortex (V1) and its relationship with various parameters. We found a strong correlation between circular variance (CV) and orthogonal-topreferred response ratio (O/P ratio), and a moderate correlation between tuning width and O/P ratio. Moreover, the suppression far from the peak that accounted for the lower CV in cat V1 cells also contributed to the narrowing of the tuning width of cells. We also studied the dependence of orientation selectivity on the modulation ratio for each cell, which is consistent with robust entrainment of the neuronal response to the phase of the drifting grating stimulus. In conclusion, the CV (global measure) and tuning width (local measure) are signifi cantly correlated with the modulation ratio.

Orientation selectivity is ubiquitous in the primary visual cortex (V1) of mammals. In cats and monkeys, V1 displays spatially ordered maps of orientation preference. Instead, in mice, squirrels, and rats, orientation selective neurons in V1 are not spatially organized, giving rise to a seemingly random pattern usually referred to as a salt-and-pepper layout. The fact that such different organizations can sharpen orientation tuning leads to question the structural role of the intracortical connections; specifically the influence of plasticity and the generation of functional connectivity. In this work, we analyze the effect of plasticity processes on orientation selectivity for both scenarios. We study a computational model of layer 2/3 and a reduced one-dimensional model of orientation selective neurons, both in the balanced state. We analyze two plasticity mechanisms. The first one involves spike-timing dependent plasticity (STDP), while the second one considers the reconnection of the interactions according to the preferred orientations of the neurons. We find that under certain conditions STDP can indeed improve selectivity but it works in a somehow unexpected way, that is, effectively decreasing the modulated part of the intracortical connectivity as compared to the non-modulated part of it. For the reconnection mechanism we find that increasing functional connectivity leads, in fact, to a decrease in orientation selectivity if the network is in a stable balanced state. Both counterintuitive results are a consequence of the dynamics of the balanced state. We also find that selectivity can increase due to a reconnection process if the resulting connections give rise to an unstable balanced state. We compare these findings with recent experimental results.

A common feature of the mammalian striate cortex is the arrangement of 'orientation domains' containing neurons preferring similar stimulus orientations. They are arranged as spokes of a pinwheel that converge at singularities known as 'pinwheel centers'. We propose that a cortical network of feedforward and intracortical lateral connections elaborates a full set of optimum orientations from geniculate inputs that show a bias to stimulus orientation and form a set of two or a small number of 'Cartesian' coordinates. Because each geniculate afferent carries signals only from one eye and its receptive field (RF) is either ON or OFF center, the network constructs also ocular dominance columns and a quasi-segregation of ON and OFF responses across the horizontal extent of the striate cortex., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Over the past decade, the mouse has emerged as an important model system for studying cortical function, owing to the advent of powerful tools that can record and manipulate neural activity in intact neural circuits. This advance has been particularly prominent in the visual cortex, where studies in the mouse have begun to bridge the gap between cortical structure and function, allowing investigators to determine the circuits that underlie specific visual computations. This review describes the advances in our understanding of the mouse visual cortex, including neural coding, the role of different cell types, and links between vision and behavior, and discusses how recent findings and new approaches can guide future studies.

Despite accounting for about 20% of all the layer 2/3 inhibitory interneurons, the vasoactive intestinal polypeptide (VIP) expressing neurons remain the least thoroughly studied of the major inhibitory subtypes. In recent studies, VIP neurons have been shown to be activated by a variety of cortico-cortical and neuromodulatory inputs, but their basic sensory response properties remain poorly characterized. We set out to explore the functional properties of layer 2/3 VIP neurons in the primary visual (V1) and primary auditory cortex (A1), using two-photon imaging guided patch recordings. We found that in the V1, VIP neurons were generally broadly tuned, with their sensory response properties resembling those of parvalbumin (PV) expressing neurons. With the exception of response latency, they did not exhibit a significant difference from PV neurons across any of the properties tested, including overlap index, response modulation, orientation selectivity, and direction selectivity. In the A1, on the other hand, VIP neurons had a strong tendency to be intensity selective, which is a property associated with a subset of putative pyramidal cells and virtually absent in PV neurons. VIP neurons had a best intensity that was significantly lower than that of PV and putative pyramidal neurons. Finally, sensory evoked spike responses of VIP neurons were delayed relative to pyramidal and PV neurons in both the V1 and A1. Combined, these results demonstrate that the sensory response properties of VIP neurons do not fit a simple model of being either PV-like broadly tuned or pyramidal-like narrowly tuned. Instead, the selectivity pattern varies with sensory area and can even be, as in the case of low sound intensity responsiveness, distinct from both PV and pyramidal neurons.

The laminar structure and conserved cellular organization of mouse visual cortex provide a useful model to determine the mechanisms underlying the development of visual system function. However, the normal development of many receptive field properties has not yet been thoroughly quantified, particularly with respect to layer identity and in the absence of anesthesia. Here, we use multisite electrophysiological recording in the awake mouse across an extended period of development, starting at eye opening, to measure receptive field properties and behavioral-state modulation of responsiveness. We find selective responses for orientation, direction, and spatial frequency at eye opening, which are similar across cortical layers. After this initial similarity, we observe layer-specific maturation of orientation selectivity, direction selectivity, and linearity over the following week. Developmental increases in selectivity are most robust and similar between layers 2-4, whereas layers 5 and 6 undergo distinct refinement patterns. Finally, we studied layer-specific behavioral-state modulation of cortical activity and observed a striking reorganization in the effects of running on response gain. During week 1 after eye opening, running increases responsiveness in layers 4 and 5, whereas in adulthood, the effects of running are most pronounced in layer 2/3. Together, these data demonstrate that response selectivity is present in all layers of the primary visual cortex (V1) at eye opening in the awake mouse and identify the features of basic V1 function that are further shaped over this early developmental period in a layer-specific manner., (Copyright © 2015 the authors 0270-6474/15/353370-14$15.00/0.)

The convergence of eye-specific thalamic inputs to visual cortical neurons forms the basis of binocular vision. Inputs from the same eye that signal light increment (On) and decrement (Off) are spatially segregated into subregions, giving rise to cortical receptive fields (RFs) that are selective for stimulus orientation. Here we map RFs of binocular neurons in the mouse primary visual cortex using spike-triggered average. We find that subregions of the same sign (On-On and Off-Off) preferentially overlap between the 2 monocular RFs, leading to binocularly matched orientation tuning. We further demonstrate that such subregion correspondence and the consequent matching of RF orientation are disrupted in mice reared in darkness during development. Surprisingly, despite the lack of all postnatal visual experience, a substantial degree of subregion correspondence still remains. In addition, dark-reared mice show normal monocular RF structures and binocular overlap. These results thus reveal the specific roles of experience-dependent and -independent processes in binocular convergence and refinement of On and Off inputs onto single cortical neurons.

The amygdala is an important center for emotional behavior, and it influences other cortical regions. Long feedback projections from the amygdala to the primary visual cortex were recently reported in the cat and monkey, two animal models for vision research. However, the detailed functional roles of these extensive projections still remain largely unknown. In this study, intrinsic signal optical imaging was used to investigate the visually driven responses of the primary visual cortex of cats as focal drugs were injected into the basal nucleus of the amygdala. Both the visually evoked global signals and differential signals in the functional maps of the primary visual cortex were enhanced or reduced by glutamate-induced activation or GABA-induced deactivation of neurons in the amygdala, respectively. This modulation was found to be non-selective, consistent with the gain control mechanism-both the preferred orientation and its mapped orientation tuning width remained unchanged. The single unit recordings showed similar results supporting the above observations. These results suggest that the distal feedback signals of the amygdala enhance the primary sensory information processing in a non-selective, gain-control fashion. This provides direct neurophysiological evidence and insight for previous studies on emotional-cue related psychological studies., (© 2013 Elsevier Inc. All rights reserved.)

Visual function in humans degrades during the early stage of senescence beginning from middle 50s to 60s. To identify its underlying neural mechanisms, we investigated the aging effects on the primary visual cortex (V1) cells in early senescent (ES) monkeys (Macaca mulatta). Under anesthesia, receptive field properties of V1 cells were examined by extracellular single-unit recordings in the young adult (YA; 5-6 years old), ES (19-24 years old), and late senescent (LS; 28-32 years old) monkeys. We found clear indications of functional degradation in early senescence, including impaired stimulus selectivities, increased level of spontaneous activity and declined signal-to-noise ratio, and dynamic range of V1 cell responses. Importantly, the functional degradation in early senescence exhibited unique features that were different from the results for the LS animals, such as remarkable individual variability in orientation selectivity and unchanged peak response elicited by visual stimulation. Our results demonstrate that the function of V1 degrades during the early stage of aging in nonhuman primate, suggesting potential neural correlates for functional deficits observed in early senescence in human subjects. Moreover, these results provide new insight into the dynamics of the aging-related functional deterioration, revealing a more complex and heterogeneous picture of this process.

Neurons in the visual cortex exhibit heterogeneity in feature selectivity and the tendency to generate action potentials synchronously with other nearby neurons. By examining visual responses from cat area 17 we found that, during gamma oscillations, there was a positive correlation between each unit's sharpness of orientation tuning, strength of oscillations, and propensity towards synchronisation with other units. Using a computational model, we demonstrated that heterogeneity in the strength of rhythmic inhibitory inputs can account for the correlations between these three properties. Neurons subject to strong inhibition tend to oscillate strongly in response to both optimal and suboptimal stimuli and synchronise promiscuously with other neurons, even if they have different orientation preferences. Moreover, these strongly inhibited neurons can exhibit sharp orientation selectivity provided that the inhibition they receive is broadly tuned relative to their excitatory inputs. These results predict that the strength and orientation tuning of synaptic inhibition are heterogeneous across area 17 neurons, which could have important implications for these neurons' sensory processing capabilities. Furthermore, although our experimental recordings were conducted in the visual cortex, our model and simulation results can apply more generally to any brain region with analogous neuron types in which heterogeneity in the strength of rhythmic inhibition can arise during gamma oscillations., (© 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

In the primary visual cortex and higher-order areas, it is well known that the stimulation of areas surrounding the classical receptive field of a neuron can inhibit its responses. In the primate area middle temporal (MT), this surround suppression was shown to be spatially organized into high and low suppression modules. However, such an organization has not been demonstrated yet in the primary visual cortex. Here, we used optical imaging of intrinsic signals to spatially evaluate surround suppression in the cat visual cortex. The magnitude of the response was measured in areas 17 and 18 for stimuli with different diameters, presented at different eccentricities. Delimited regions of the cortex were revealed by circumscribed stimulations of the visual field ("cortical response field"). Increasing the stimulus diameter increased the spread of cortical activation. In the cortical response field, the optimal stimulation diameter and the level of suppression were evaluated. Most pixels (≥3/4) exhibited surround suppression profiles. The optimal diameter, corresponding to a population of receptive fields, was smaller in area 17 (22°) than in area 18 (36°) in accordance with electrophysiological data. No difference in the suppression strength was observed between both areas (A17: 25%, A18: 21%). Further analysis of our data revealed the presence of surround modulation maps, organized in low and high suppression domains. We also developed a statistical method to confirm the existence of this cortical map and its neuronal origin. The organization for center/surround suppression observed here at the level of the primary visual cortex is similar to those found in higher order areas in primates (e.g., area MT) and could represent a strategy to optimize figure ground discrimination.

Inhibitory interneurons play important roles in the development of brain functions. In the visual cortex, functional maturation of inhibitory interneurons is essential for ocular dominance plasticity. However, roles of inhibitory interneurons in the development of orientation and direction selectivity, fundamental properties of primary visual cortex, are less understood. We examined orientation and direction selectivity of neurons in GAD67-GFP (Δneo) mice, in which expression of GABA in the brain is decreased in the newborn. We used in vivo two-photon calcium imaging to examine visual response of neurons in these mice and found that long-term decrease of GABA led to increase of response amplitude to non-preferred orientation of visual stimuli, which decreased orientation selectivity. In contrast, direction selectivity was not affected. These results suggest that orientation selectivity is decreased in mice with GABA down-regulation during development.

The brain combines two-dimensional images received from the two eyes to form a percept of three-dimensional surroundings. This process of binocular integration in the primary visual cortex (V1) serves as a useful model for studying how neural circuits generate emergent properties from multiple input signals. Here, we perform a thorough characterization of binocular integration using electrophysiological recordings in the V1 of awake adult male and female mice by systematically varying the orientation and phase disparity of monocular and binocular stimuli. We reveal widespread binocular integration in mouse V1 and demonstrate that the three commonly studied binocular properties—ocular dominance, interocular matching, and disparity selectivity—are independent of each other. For individual neurons, the responses to monocular stimulation can predict the average amplitude of binocular response but not its selectivity. Finally, the extensive and independent binocular integration of monocular inputs is seen across cortical layers in both regular-spiking and fast-spiking neurons, regardless of stimulus design. Our data indicate that the current model of simple feedforward convergence is inadequate to account for binocular integration in mouse V1, thus suggesting an indispensable role played by intracortical circuits in binocular computation. [ABSTRACT FROM AUTHOR]

Extracellular recordings were made from 642 units in the primary visual cortex (V1) of a highly visual marsupial, the Tammar wallaby. The receptive field (RF) characteristics of the cells were objectively estimated using the non-linear input model (NIM), and these were correlated with spike shapes. We found that wallaby cortical units had 68% regular spiking (RS), 12% fast spiking (FS), 4% triphasic spiking (TS), 5% compound spiking (CS) and 11% positive spiking (PS). RS waveforms are most often associated with recordings from pyramidal or spiny stellate cell bodies, suggesting that recordings from these cell types dominate in the wallaby cortex. In wallaby, 70-80% of FS and RS cells had orientation selective RFs and had evenly distributed linear and nonlinear RFs. We found that 47% of wallaby PS units were non-orientation selective and they were dominated by linear RFs. Previous studies suggest that the PS units represent recordings from the axon terminals of non-orientation selective cells originating in the lateral geniculate nucleus (LGN). If this is also true in wallaby, as strongly suggested by their low response latencies and bursty spiking properties, the results suggest that significantly more neurons in wallaby LGN are already orientation selective. In wallaby, less than 10% of recorded spikes had triphasic (TS) or sluggish compound spiking (CS) waveforms. These units had a mixture of orientation selective and non-oriented properties, and their cellular origins remain difficult to classify. [ABSTRACT FROM AUTHOR]

The brain creates a single visual percept of the world with inputs from two eyes. This means that downstream structures must integrate information from the two eyes coherently. Not only does the brain meet this challenge effortlessly, it also uses small differences between the two eyes' inputs, i.e., binocular disparity, to construct depth information in a perceptual process called stereopsis. Recent studies have advanced our understanding of the neural circuits underlying stereoscopic vision and its development. Here, we review these advances in the context of three binocular properties that have been most commonly studied for visual cortical neurons: ocular dominance of response magnitude, interocular matching of orientation preference, and response selectivity for binocular disparity. By focusing mostly on mouse studies, as well as recent studies using ferrets and tree shrews, we highlight unresolved controversies and significant knowledge gaps regarding the neural circuits underlying binocular vision. We note that in most ocular dominance studies, only monocular stimulations are used, which could lead to a mischaracterization of binocularity. On the other hand, much remains unknown regarding the circuit basis of interocular matching and disparity selectivity and its development. We conclude by outlining opportunities for future studies on the neural circuits and functional development of binocular integration in the early visual system. [ABSTRACT FROM AUTHOR]