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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 superior colliculus (SC) is the most prominent visual center in mice. Studies over the past decade have greatly advanced our understanding of the function, organization, and development of the mouse SC, which has rapidly become a popular model in vision research. These studies have described the diverse and cell-type-specific visual response properties in the mouse SC, revealed their laminar and topographic organizations, and linked the mouse SC and downstream pathways with visually guided behaviors. Here, we summarize these findings, compare them with the rich literature of SC studies in other species, and highlight important gaps and exciting future directions. Given its clear importance in mouse vision and the available modern neuroscience tools, the mouse SC holds great promise for understanding the cellular, circuit, and developmental mechanisms that underlie visual processing, sensorimotor transformation, and, ultimately, behavior.

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.

One leading hypothesis on the nature of visual callosal connections (CC) is that they replicate features of intrahemispheric lateral connections. However, CC act also in the central part of the binocular visual field. In agreement, early experiments in cats indicated that they provide the ipsilateral eye part of binocular receptive fields (RFs) at the vertical midline (Berlucchi and Rizzolatti, 1968), and play a key role in stereoscopic function. But until today callosal inputs to receptive fields activated by one or both eyes were never compared simultaneously, because callosal function has been often studied by cutting or lesioning either corpus callosum or optic chiasm not allowing such a comparison. To investigate the functional contribution of CC in the intact cat visual system we recorded both monocular and binocular neuronal spiking responses and receptive fields in the 17/18 transition zone during reversible deactivation of the contralateral hemisphere. Unexpectedly from many of the previous reports, we observe no change in ocular dominance during CC deactivation. Throughout the transition zone, a majority of RFs shrink, but several also increase in size. RFs are significantly more affected for ipsi- as opposed to contralateral stimulation, but changes are also observed with binocular stimulation. Noteworthy, RF shrinkages are tiny and not correlated to the profound decreases of monocular and binocular firing rates. They depend more on orientation and direction preference than on eccentricity or ocular dominance of the receiving neuron's RF. Our findings confirm that in binocularly viewing mammals, binocular RFs near the midline are constructed via the direct geniculo-cortical pathway. They also support the idea that input from the two eyes complement each other through CC: Rather than linking parts of RFs separated by the vertical meridian, CC convey a modulatory influence, reflecting the feature selectivity of lateral circuits, with a strong cardinal bias.

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.)

Visual information is already processed in the retina before it is transmitted to higher visual centers in the brain. This includes the extraction of salient features from visual scenes, such as motion directionality or contrast, through neurons belonging to distinct neural circuits. Some retinal neurons are tuned to the orientation of elongated visual stimuli. Such 'orientation-selective' neurons are present in the retinae of most, if not all, vertebrate species analyzed to date, with species-specific differences in frequency and degree of tuning. In some cases, orientation-selective neurons have very stereotyped functional and morphological properties suggesting that they represent distinct cell types. In this review, we describe the retinal cell types underlying orientation selectivity found in various vertebrate species, and highlight their commonalities and differences. In addition, we discuss recent studies that revealed the cellular, synaptic and circuit mechanisms at the basis of retinal orientation selectivity. Finally, we outline the significance of these findings in shaping our current understanding of how this fundamental neural computation is implemented in the visual systems of vertebrates.

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.)

Intrinsic signal optical imaging reveals a highly modular map of orientation preference in the primary visual cortex (V1) of several species. This orientation map is characterized by domains and pinwheels where local circuitry is either more or less orientation selective, respectively. It has now been repeatedly demonstrated that neurons in pinwheels tend to be more broadly tuned to orientation, likely due to the broad range of orientation preference of the neighboring neurons forming pinwheels. However, certain stimulus conditions, such as a decrease in contrast or an increase in size, significantly sharpen tuning widths of V1 neurons. Here, we find that pinwheel neuron tuning widths are broader than domain neurons only for high contrast, optimally sized stimuli, conditions that maximize excitation through feedforward, and local cortical processing. When contrast was lowered or size increased, orientation tuning width sharpened and became equal. These latter conditions are conducive to less local excitation either through lower feedforward drive or by surround suppression arising from long-range cortical circuits. Tuning width differences between pinwheel and domain neurons likely arise through more local circuitry and are overcome through recruitment of longer-range cortical circuits.

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.)

Primate posterior parietal cortex (PPC) is known to be involved in controlling spatial attention. Neurons in one part of the PPC, the lateral intraparietal area (LIP), show enhanced responses to objects at attended locations. Although many are selective for object features, such as the orientation of a visual stimulus, it is not clear how LIP circuits integrate feature-selective information when providing attentional feedback about behaviorally relevant locations to the visual cortex. We studied the relationship between object feature and spatial attention properties of LIP cells in two macaques by measuring the cells' orientation selectivity and the degree of attentional enhancement while performing a delayed match-to-sample task. Monkeys had to match both the location and orientation of two visual gratings presented separately in time. We found a wide range in orientation selectivity and degree of attentional enhancement among LIP neurons. However, cells with significant attentional enhancement had much less orientation selectivity in their response than cells which showed no significant modulation by attention. Additionally, orientation-selective cells showed working memory activity for their preferred orientation, whereas cells showing attentional enhancement also synchronized with local neuronal activity. These results are consistent with models of selective attention incorporating two stages, where an initial feature-selective process guides a second stage of focal spatial attention. We suggest that LIP contributes to both stages, where the first stage involves orientation-selective LIP cells that support working memory of the relevant feature, and the second stage involves attention-enhanced LIP cells that synchronize to provide feedback on spatial priorities., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

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.

Sensory-driven behaviors engage a cascade of cortical regions to process sensory input and generate motor output. To investigate the temporal dynamics of neural activity at this global scale, we have improved and integrated tools to perform functional imaging across large areas of cortex using a transgenic mouse expressing the genetically encoded calcium sensor GCaMP6s, together with a head-fixed visual discrimination behavior. This technique allows imaging of activity across the dorsal surface of cortex, with spatial resolution adequate to detect differential activity in local regions at least as small as 100 μm. Imaging during an orientation discrimination task reveals a progression of activity in different cortical regions associated with different phases of the task. After cortex-wide patterns of activity are determined, we demonstrate the ability to select a region that displayed conspicuous responses for two-photon microscopy and find that activity in populations of individual neurons in that region correlates with locomotion in trained mice. We expect that this paradigm will be a useful probe of information flow and network processing in brain-wide circuits involved in many sensory and cognitive processes., (Copyright © 2016 the American Physiological Society.)

Orientation selectivity (OS) is a prominent and well studied feature of early visual processing in mammals, but recent work has highlighted the possibility that parallel OS circuits might exist in multiple brain locations. Although both classic and modern work has identified an OS mechanism in selective wiring from lateral geniculate nucleus (LGN) to primary visual cortex, OS responses have now been found upstream of cortex in mouse LGN and superior colliculus, suggesting a possible origin in the retina. Indeed, retinal OS responses have been reported for decades in rabbit and more recently in mouse. However, we still know very little about the properties and mechanisms of retinal OS in the mouse, including whether there is a distinct OS ganglion cell type, which orientations are represented, and what are the synaptic mechanisms of retinal OS. We have identified two novel types of OS ganglion cells in the mouse retina that are highly selective for horizontal and vertical cardinal orientations. Reconstructions of the dendritic trees of these OS ganglion cells and measurements of their synaptic conductances offer insights into the mechanism of the OS computation at the earliest stage of the visual system., Significance Statement: Orientation selectivity (OS) is one of the most well studied computations in the brain and has become a prominent model system in various areas of sensory neuroscience. Although the cortical mechanism of OS suggested by Hubel and Wiesel (1962) has been investigated intensely, other OS cells exist upstream of cortex as early as the retina and the mechanisms of OS in subcortical regions are much less well understood. We identified two ON retinal ganglion cells (RGCs) in mouse that compute OS along the horizontal (nasal-temporal) and vertical (dorsoventral) axes of visual space. We show the relationship between dendritic morphology and OS for each RGC type and reveal new synaptic mechanisms of OS computation in the retina., (Copyright © 2016 the authors 0270-6474/16/363208-14$15.00/0.)

The ability to extract the shape of moving objects is fundamental to visual perception. However, where such computations are processed in the visual system is unknown. To address this question, we used intrinsic signal optical imaging in awake monkeys to examine cortical response to perceptual contours defined by motion contrast (motion boundaries, MBs). We found that MB stimuli elicit a robust orientation response in area V2. Orientation maps derived from subtraction of orthogonal MB stimuli aligned well with the orientation maps obtained with luminance gratings (LGs). In contrast, area V1 responded well to LGs, but exhibited a much weaker orientation response to MBs. We further show that V2 direction domains respond to motion contrast, which is required in the detection of MB in V2. These results suggest that V2 represents MB information, an important prerequisite for shape recognition and figure-ground segregation., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

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.)

Much of the computational power of the retina derives from the activity of amacrine cells, a large and diverse group of GABAergic and glycinergic inhibitory interneurons. Here, we identify an ON-type orientation-selective, wide-field, polyaxonal amacrine cell (PAC) in the rabbit retina and demonstrate how its orientation selectivity arises from the structure of the dendritic arbor and the pattern of excitatory and inhibitory inputs. Excitation from ON bipolar cells and inhibition arising from the OFF pathway converge to generate a quasi-linear integration of visual signals in the receptive field center. This serves to suppress responses to high spatial frequencies, thereby improving sensitivity to larger objects and enhancing orientation selectivity. Inhibition also regulates the magnitude and time course of excitatory inputs to this PAC through serial inhibitory connections onto the presynaptic terminals of ON bipolar cells. This presynaptic inhibition is driven by graded potentials within local microcircuits, similar in extent to the size of single bipolar cell receptive fields. Additional presynaptic inhibition is generated by spiking amacrine cells on a larger spatial scale covering several hundred microns. The orientation selectivity of this PAC may be a substrate for the inhibition that mediates orientation selectivity in some types of ganglion cells. Significance statement: The retina comprises numerous excitatory and inhibitory circuits that encode specific features in the visual scene, such as orientation, contrast, or motion. Here, we identify a wide-field inhibitory neuron that responds to visual stimuli of a particular orientation, a feature selectivity that is primarily due to the elongated shape of the dendritic arbor. Integration of convergent excitatory and inhibitory inputs from the ON and OFF visual pathways suppress responses to small objects and fine textures, thus enhancing selectivity for larger objects. Feedback inhibition regulates the strength and speed of excitation on both local and wide-field spatial scales. This study demonstrates how different synaptic inputs are regulated to tune a neuron to respond to specific features in the visual scene., (Copyright © 2015 the authors 0270-6474/15/3513336-15$15.00/0.)

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.

Although the basis of our knowledge of experience-dependent plasticity comes from studies on carnivores and primates, studies examining the physiological and molecular mechanisms that underlie development and plasticity have increasingly employed mice. We have used several common rearing paradigms, such as dark-rearing and monocular deprivation (MD), to examine the timing of the physiological and molecular changes to altered experience in the cat primary visual cortex. Dark-rearing from birth or for 1 week starting at 4 weeks of age produced a similar reduction in the amplitude of responses measured through intrinsic signal imaging and a reduction in orientation selectivity. One week of visual experience following dark-rearing until 4 weeks of age yielded normal responses in both amplitude and orientation selectivity. The depression of deprived-eye responses was similar in magnitude after 2 and 7 days of MD. In contrast, non-deprived-eye responses almost doubled in magnitude after 7 days compared with 2 days of MD. These changes in the functional properties of primary visual cortex neurons were mirrored by specific changes in synaptic protein expression. Changes in proteins such as the NR2A and NR2B subunits of the N-methyl-D-aspartate receptor, postsynaptic density protein 95, alpha-CA2+/calmodulin-dependent protein kinase II (αCaMKII), and GABAAα1a indicated that the levels of sensory activity regulated mechanisms associated with both excitatory (NR2A and NR2B) and inhibitory (GABAAα1a) transmission so as to maintain response homeostasis. Additionally, we found that MD regulated the AMPA receptor glutamate (GluR1) subunit as well as signalling molecules (αCaMKII and synaptic Ras GTPase activating protein, SynGAP) downstream of N-methyl-D-aspartate receptors. Proteins in a common signalling pathway appeared to have similar developmental expression profiles that were broadly similar between cats and rodents. [ABSTRACT FROM AUTHOR]

An abstract of the article "The Generation of Receptive-Field Structure in Cat Primary Visual Cortex," by L. M. Martinez is presented.

Abstract Circumscribed retinal lesions in adult cats result in a reorganization of circuitry in area 17 such that neurons in the lesion projection zone (LPZ) can now be activated, not from their original receptive fields (RFs) but from regions of normal retina adjacent to the lesion (‘ectopic’ RFs). We have studied this phenomenon further by making circumscribed monocular retinal lesions in 8-week-old kittens and recording responses to visual stimuli of neurons in the LPZ of area 17 when these cats reached adulthood. These responses have been compared with those in adult-lesioned cats either of relatively short postlesion survival (2–24 weeks) or long postlesion survival (3.5–4.5 years). In both kitten-lesioned and adult-lesioned animals most LPZ neurons recorded from the supragranular layers (II and III) not only exhibited new ectopic RFs when stimuli were presented via the lesioned eye but the RF properties (e.g. the sizes of excitatory RFs, orientation and direction selectivities, velocity preferences and upper cut-off velocities) were often indistinguishable from those seen when stimuli were presented via the nonlesioned eye. Similarly, in both kitten-lesioned and adult-lesioned animals, most LPZ neurons recorded from the granular and infragranular layers (IV, V, VI), like those recorded from the supragranular layers, were binocular. However, in adult-lesioned but not in kitten-lesioned animals, the responses and the upper cut-off velocities of LPZ cells recorded from the granular and infragranular layers to stimuli presented via ectopic RFs tended to be, respectively, substantially weaker and lower than those for stimuli presented via the nonlesioned eye. The age-related laminar differences in reorganizational plasticity of cat striate cortex correlate with the lamino-temporal pattern of distribution of N -methyl-d-aspartate glutamate receptors in striate cortex. [ABSTRACT FROM AUTHOR]

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.

Visual neurons in the superior colliculus (SC) respond to both bright (On) and dark (Off) stimuli in their receptive fields. This receptive field property is due to proper convergence of On- and Off-centered retinal ganglion cells to their target cells in the SC. In this study, we have compared the receptive field structure of individual SC neurons in two lines of mutant mice that are deficient in retinotopic mapping: the ephrin-A knockouts that lack important retinocollicular axonal guidance cues and the nAChR-β2 knockouts that have altered activity-dependent refinement of retinocollicular projections. We find that even though the receptive fields are much larger in the ephrin-A knockouts, their On-Off overlap remains unchanged. These neurons also display normal level of selectivity for stimulus direction and orientation. In contrast, the On-Off overlap is disrupted in the β2 knockouts. Together with the previous finding of disrupted direction and orientation selectivity in the β2 knockout mice, our results indicate that molecular guidance cues and activity-dependent processes play different roles in the development of receptive field properties in the SC.

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.

The orientation of a large grating can be decoded from V1 functional magnetic resonance imaging (fMRI) data, even at low resolution (3-mm isotropic voxels). This finding has suggested that columnar-level neuronal information might be accessible to fMRI at 3T. However, orientation decodability might alternatively arise from global orientation-preference maps. Such global maps across V1 could result from bottom-up processing, if the preferences of V1 neurons were biased toward particular orientations (e.g., radial from fixation, or cardinal, i.e., vertical or horizontal). Global maps could also arise from local recurrent or top-down processing, reflecting pre-attentive perceptual grouping, attention spreading, or predictive coding of global form. Here we investigate whether fMRI orientation decoding with 2-mm voxels requires (a) globally coherent orientation stimuli and/or (b) global-scale patterns of V1 activity. We used opposite-orientation gratings (balanced about the cardinal orientations) and spirals (balanced about the radial orientation), along with novel patch-swapped variants of these stimuli. The two stimuli of a patch-swapped pair have opposite orientations everywhere (like their globally coherent parent stimuli). However, the two stimuli appear globally similar, a patchwork of opposite orientations. We find that all stimulus pairs are robustly decodable, demonstrating that fMRI orientation decoding does not require globally coherent orientation stimuli. Furthermore, decoding remained robust after spatial high-pass filtering for all stimuli, showing that fine-grained components of the fMRI patterns reflect visual orientations. Consistent with previous studies, we found evidence for global radial and vertical preference maps in V1. However, these were weak or absent for patch-swapped stimuli, suggesting that global preference maps depend on globally coherent orientations and might arise through recurrent or top-down processes related to the perception of global form.

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.

Genetically encoded calcium indicators (GECIs) allow repeated, non-invasive measurements of neural activity in defined populations of neurons, but until recently GECIs based on single fluorescent proteins have been limited to the green region of the color spectrum. Recent efforts in protein engineering have expanded the color palette of GECIs. One of these new GECIs, the red RGECO, is spectrally separate from the traditional GFP-based sensors such as GCaMP, and therefore opens the way for simultaneous, multicolor imaging of neural activity. While RGECO has been shown to report spontaneous calcium fluctuations in neurons, the precise relationship of RGECO signal to evoked-neural activity is not known. Measurements of neural activity using RGECO in vivo have also not been reported. Using dissociated hippocampal neurons we performed a systematic analysis of two forms of RGECO- a cytosolic form and a presynaptically localized form generated by fusion of RGECO to the presynaptic protein, synaptophysin (SyRGECO). We find that RGECO and GCaMP3 are comparable in terms of dynamic range, signal-to-noise ratios and kinetics but that RGECO is a more reliable reporter of single action potentials. In terms of performance SyGCaMP3 and SyRGECO are comparable, and both are more sensitive reporters of activity than the cytosolic form of each probe. Using the zebrafish retinotectal system we show that SyRGECO and RGECO are can report neural activity in vivo and that RGECO expression permits detailed structural analysis of neuronal arbors. We have exploited these attributes to provide a morphological and functional description of tectal cells selective for motion along the vertical axis. These results open up the possibility of using zebrafish to functionally image genetically defined pre- and postsynaptic circuit components, separable by color, which will be a powerful approach to studying neural interactions in the brain.