Responses Of Visual Cortical Neurons Research Articles

Stimulus encoding by specific inactivation of cortical neurons

Neuronal ensembles are groups of neurons with correlated activity associated with sensory, motor, and behavioral functions. To explore how ensembles encode information, we investigated responses of visual cortical neurons in awake mice using volumetric two-photon calcium imaging during visual stimulation. We identified neuronal ensembles employing an unsupervised model-free algorithm and, besides neurons activated by the visual stimulus (termed “onsemble”), we also find neurons that are specifically inactivated (termed “offsemble”). Offsemble neurons showed faster calcium decay during stimuli, suggesting selective inhibition. In response to visual stimuli, each ensemble (onsemble+offsemble) exhibited small trial-to-trial variability, high orientation selectivity, and superior predictive accuracy for visual stimulus orientation, surpassing the sum of individual neuron activity. Thus, the combined selective activation and inactivation of cortical neurons enhances visual encoding as an emergent and distributed neural code.

Cortical mechanisms of visual brightness.

SUMMARYThe primary visual cortex signals the onset of light and dark stimuli with ON and OFF cortical pathways. Here, we demonstrate that both pathways generate similar response increments to large homogeneous surfaces and their response average increases with surface brightness. We show that, in cat visual cortex, response dominance from ON or OFF pathways is bimodally distributed when stimuli are smaller than one receptive field center but unimodally distributed when they are larger. Moreover, whereas small bright stimuli drive opposite responses from ON and OFF pathways (increased versus suppressed activity), large bright surfaces drive similar response increments. We show that this size-brightness relation emerges because strong illumination increases the size of light surfaces in nature and both ON and OFF cortical neurons receive input from ON thalamic pathways. We conclude that visual scenes are perceived as brighter when the average response increments from ON and OFF cortical pathways become stronger.

Voltage-Gated Intrinsic Conductances Shape the Input-Output Relationship of Cortical Neurons in Behaving Primate V1

Neurons are input-output (I/O) devices-they receive synaptic inputs from other neurons, integrate those inputs with their intrinsic properties, and generate action potentials as outputs. To understand this fundamental process, we studied the interaction between synaptic inputs and intrinsic properties using whole-cell recordings from V1 neurons of awake, fixating macaque monkeys. Our measurements during spontaneous activity and visual stimulation reveal an intrinsic voltage-gated conductance that profoundly alters the integrative properties and visual responses of cortical neurons. This voltage-gated conductance increases neuronal gain and selectivity with subthreshold depolarization and linearizes the relationship between synaptic input and neural output. This intrinsic conductance is found in layer 2/3 V1 neurons of awake macaques, anesthetized mice, and acute brain slices. These results demonstrate that intrinsic conductances play an essential role in shaping the I/O relationship of cortical neurons and must be taken into account in future models of cortical computations.

Searching for object pointers in the visual cortex.

We perceive objects as permanent and stable despite frequent occlusions and eye movements, but their representation in the visual cortex is neither permanent nor stable. Feature selective cells respond only as long as objects are visible, and their responses depend on eye position. We explored the hypothesis that the system maintains object pointers that provide permanence and stability. Pointers should send facilitatory signals to the feature cells of an object, and these signals should persist across temporary occlusions and remap to compensate for image displacements caused by saccades. Here, we searched for such signals in monkey areas V2 and V4 (Macaca mulatta). We developed a new paradigm in which a monkey freely inspects an array of objects in search for reward while some of the objects are being occluded temporarily by opaque drifting strips. Two types of objects were used to manipulate attention. The results were as follows. 1) Eye movements indicated a robust representation of location and type of the occluded objects; 2) in neurons of V4, but not V2, occluded objects produced elevated activity relative to blank condition; 3) the elevation of activity was reduced for objects that had been fixated immediately before the current fixation ('inhibition of return'); and 4) when attended, or when the target of a saccade, visible objects produced enhanced responses in V4, but occluded objects produced no modulation. Although results 1-3 confirm the hypothesis, the absence of modulation under occlusion is not consistent. Further experiments are needed to resolve this discrepancy.NEW & NOTEWORTHY The way we perceive objects as permanent contrasts with the short-lived responses of visual cortical neurons. A theory postulates pointers that give objects continuity, predicting a class of neurons that respond not only to visual objects but also when an occluded object moves into their receptive field. Here, we tested this theory with a novel paradigm in which a monkey freely scans an array of objects while some of them are transiently occluded.

Prefrontal Corticotectal Neurons Enhance Visual Processing through the Superior Colliculus and Pulvinar Thalamus

Top-down modulation of visual processing is mediated in part by direct prefrontal to visual cortical projections. Here, we show that the mouse cingulate cortex (Cg) regulates visual processing not only through corticocortical neurons projecting to the visual cortex but also through corticotectal neurons projecting subcortically. Bidirectional optogenetic manipulation demonstrated a prominent contribution of Cg corticotectal neurons to visually guided behavior, which is mediated by their collateral projections to both the motor-related layers of the superior colliculus (SC) and the lateral posterior nucleus ofthe thalamus (LP, analogous to the primate pulvinar). Whereas the Cg innervates the anterior LP (LPa), the SC innervates the posterior LP (LPp). Activating each stage of the Cg→SC→LPp or the Cg→LPa pathway strongly enhanced visual performance of the mouse and the sensory responses of visual cortical neurons. These results delineate two subcortical pathways by which a subtype of prefrontal pyramidal neurons exerts a powerful top-down influence on visual processing. VIDEO ABSTRACT.

A Computational Analysis of the Function of Three Inhibitory Cell Types in Contextual Visual Processing

Most cortical inhibitory cell types exclusively express one of three genes, parvalbumin, somatostatin and 5HT3a. We conjecture that these three inhibitory neuron types possess distinct roles in visual contextual processing based on two observations. First, they have distinctive synaptic sources and targets over different spatial extents and from different areas. Second, the visual responses of cortical neurons are affected not only by local cues, but also by visual context. We use modeling to relate structural information to function in primary visual cortex (V1) of the mouse, and investigate their role in contextual visual processing. Our findings are three-fold. First, the inhibition mediated by parvalbumin positive (PV) cells mediates local processing and could underlie their role in boundary detection. Second, the inhibition mediated by somatostatin-positive (SST) cells facilitates longer range spatial competition among receptive fields. Third, non-specific top-down modulation to interneurons expressing vasoactive intestinal polypeptide (VIP), a subclass of 5HT3a neurons, can selectively enhance V1 responses.

Visual experience regulates the development of long-term synaptic modifications induced by low-frequency stimulation in mouse visual cortex

Manipulation of visual experience can considerably modify visual responses of visual cortical neurons even in adulthood in the mouse, although the modification is less profound than that observed during the critical period. Our previous studies demonstrated that low-frequency (2Hz) stimulation for 15min applied to layer 4 induces T-type Ca2+ channel-dependent long-term potentiation (LTP) at excitatory synapses in layer 2/3 neurons of visual cortex during the critical period. In this study, we investigated whether low-frequency stimulation could induce synaptic plasticity in adult mice. We found that 2Hz stimulation induced LTP of extracellular field potentials evoked by stimulation of layer 4 in layer 2/3 in adulthood as during the critical period. LTP in adulthood was blocked by L-type, but not T-type, Ca2+ channel antagonists, whereas LTP during the critical period was blocked by T-type, but not L-type, Ca2+ channel antagonists. This developmental change in LTP was prevented by dark rearing. Under pharmacological blockade of GABAA receptors, T-type Ca2+ channel-dependent LTP occurred, whereas L-type Ca2+ channel-dependent LTP did not occur. These results suggest that different forms of synaptic plasticity can contribute separately to experience-dependent modification of visual responses during the critical period and in adulthood.

Modulation of Neuronal Responses by Exogenous Attention in Macaque Primary Visual Cortex.

Visual perception is influenced by attention deployed voluntarily or triggered involuntarily by salient stimuli. Modulation of visual cortical processing by voluntary or endogenous attention has been extensively studied, but much less is known about how involuntary or exogenous attention affects responses of visual cortical neurons. Using implanted microelectrode arrays, we examined the effects of exogenous attention on neuronal responses in the primary visual cortex (V1) of awake monkeys. A bright annular cue was flashed either around the receptive fields of recorded neurons or in the opposite visual field to capture attention. A subsequent grating stimulus probed the cue-induced effects. In a fixation task, when the cue-to-probe stimulus onset asynchrony (SOA) was <240 ms, the cue induced a transient increase of neuronal responses to the probe at the cued location during 40-100 ms after the onset of neuronal responses to the probe. This facilitation diminished and disappeared after repeated presentations of the same cue but recurred for a new cue of a different color. In another task to detect the probe, relative shortening of monkey's reaction times for the validly cued probe depended on the SOA in a way similar to the cue-induced V1 facilitation, and the behavioral and physiological cueing effects remained after repeated practice. Flashing two cues simultaneously in the two opposite visual fields weakened or diminished both the physiological and behavioral cueing effects. Our findings indicate that exogenous attention significantly modulates V1 responses and that the modulation strength depends on both novelty and task relevance of the stimulus. Significance statement: Visual attention can be involuntarily captured by a sudden appearance of a conspicuous object, allowing rapid reactions to unexpected events of significance. The current study discovered a correlate of this effect in monkey primary visual cortex. An abrupt, salient, flash enhanced neuronal responses, and shortened the animal's reaction time, to a subsequent visual probe stimulus at the same location. However, the enhancement of the neural responses diminished after repeated exposures to this flash if the animal was not required to react to the probe. Moreover, a second, simultaneous, flash at another location weakened the neuronal and behavioral effects of the first one. These findings revealed, beyond the observations reported so far, the effects of exogenous attention in the brain.

Control of response reliability by parvalbumin-expressing interneurons in visual cortex.

The responses of visual cortical neurons to natural stimuli are both reliable and sparse. These properties require inhibition, yet the contribution of specific types of inhibitory neurons is not well understood. Here we demonstrate that optogenetic suppression of parvalbumin (PV)- but not somatostatin (SOM)-expressing interneurons reduces response reliability in the primary visual cortex of anaesthetized and awake mice. PV suppression leads to increases in the low firing rates and decreases in the high firing rates of cortical neurons, resulting in an overall reduction of the signal-to-noise ratio (SNR). In contrast, SOM suppression generally increases the overall firing rate for most neurons, without affecting the SNR. Further analysis reveals that PV, but not SOM, suppression impairs neural discrimination of natural stimuli. Together, these results reveal a critical role for PV interneurons in the formation of reliable visual cortical representations of natural stimuli.

3D Clustering of GABAergic Neurons Enhances Inhibitory Actions on Excitatory Neurons in the Mouse Visual Cortex

Neocortical neurons with similar functional properties assemble into spatially coherent circuits, but itremains unclear how inhibitory interneurons are organized. We applied invivo two-photon functional Ca(2+) imaging and whole-cell recording of synaptic currents to record visual responses of cortical neurons and analyzed their spatial arrangements. GABAergic interneurons were clustered in the 3D space of the mouse visual cortex, and excitatory neurons located within the clusters (insiders) had alower amplitude and sharper orientation tuning of visual responses than outsiders. Inhibitory synaptic currents recorded from the insiders were larger than those of the outsiders. Single, isolated interneurons did not show such a location-tuning/amplitude relationship. The two principal subtypes of interneurons, parvalbumin- and somatostatin-expressing neurons, also formed clusters with only slightly overlapping each other and exhibited a different location-tuning relationship. These findings suggest that GABAergic interneurons and their subgroups form clusters to make their inhibitory function more effective than isolated interneurons.

Curtailing effect of awakening on visual responses of cortical neurons by cholinergic activation of inhibitory circuits.

Visual responsiveness of cortical neurons changes depending on the brain state. Neural circuit mechanism underlying this change is unclear. By applying the method of in vivo two-photon functional calcium imaging to transgenic rats in which GABAergic neurons express fluorescent protein, we analyzed changes in visual response properties of cortical neurons when animals became awakened from anesthesia. In the awake state, the magnitude and reliability of visual responses of GABAergic neurons increased whereas the decay of responses of excitatory neurons became faster. To test whether the basal forebrain (BF) cholinergic projection is involved in these changes, we analyzed effects of electrical and optogenetic activation of BF on visual responses of mouse cortical neurons with in vivo imaging and whole-cell recordings. Electrical BF stimulation in anesthetized animals induced the same direction of changes in visual responses of both groups of neurons as awakening. Optogenetic activation increased the frequency of visually evoked action potentials in GABAergic neurons but induced the delayed hyperpolarization that ceased the late generation of action potentials in excitatory neurons. Pharmacological analysis in slice preparations revealed that photoactivation-induced depolarization of layer 1 GABAergic neurons was blocked by a nicotinic receptor antagonist, whereas non-fast-spiking layer 2/3 GABAergic neurons was blocked only by the application of both nicotinic and muscarinic receptor antagonists. These results suggest that the effect of awakening is mediated mainly through nicotinic activation of layer 1 GABAergic neurons and mixed nicotinic/muscarinic activation of layer 2/3 non-fast-spiking GABAergic neurons, which together curtails the visual responses of excitatory neurons.

A linear-nonlinear model accurately predicts cortical responses to simultaneous electrical stimulation with a retinal implant

Retinal implants for restoring partial vision to people with degenerative photoreceptor diseases consist of an array of electrodes implanted on the retina which can be driven according to images captured by a camera via stimulation electronics. In the past two decades this technology has progressed from prototypes, through clinical trials, through to the first commercial devices available in the U.S. last year (2013). Currently, the functional benefit to patients is largely as an aid to mobility and navigation. Improved outcomes, for example to the ability to perform useful object recognition, will likely require higher density electrode arrays. There is also likely to be benefit from attaining greater spatial control of electrically evoked neural activity by choosing appropriate stimulation parameters. As a first step towards this goal we investigated the ability of simple linear-nonlinear models to capture the response of visual cortical neurons driven by a retinal implant. Using an electrode array containing 21 platinum electrodes in the suprachoroidal space of the retina in an anaesthetized cat, spatially white and temporally sparse electrical pulses were delivered to the retina simultaneously across several electrodes. Each pulse was either an anodic-first or cathodic-first charge-balanced biphasic current pulse. Multi-unit spiking responses were recorded using 6x10 arrays (Blackrock Microsystems, UT) in the primary visual cortex. We formulated a model to predict spiking responses observed in the cortex in response to electrical stimulation of the retina. The pathway between the retina and the cortex was modelled as a set of spatial linear filters, each followed by a static nonlinearity. To encapsulate the effects of both anodic-first and cathodic-first current pulses, two different linear filters (one for anodic-first and one for cathodic-first stimuli) and their associated nonlinearities acted on the input separately. The output of these two nonlinearities was combined to produce an estimate of the spike rate at a given site in the cortex. The parameters of the model were optimized with a non-linear fitting algorithm. We used 83% of the available experimental data to fit the model parameters. After fitting the model parameters, the model accurately predicted the pulse-by-pulse spike count for the remaining 17% of the data (r=0.83). The spatial linear filter can be considered to be the weighting matrix for the effect of the stimulating electrodes on a cortical site. We anticipate that the model may provide a basis for devising ideal stimulation strategies for shaping the activity in the cortex.

The Touch and Zap method for in vivo whole-cell patch recording of intrinsic and visual responses of cortical neurons and glial cells.

Whole-cell patch recording is an essential tool for quantitatively establishing the biophysics of brain function, particularly in vivo. This method is of particular interest for studying the functional roles of cortical glial cells in the intact brain, which cannot be assessed with extracellular recordings. Nevertheless, a reasonable success rate remains a challenge because of stability, recording duration and electrical quality constraints, particularly for voltage clamp, dynamic clamp or conductance measurements. To address this, we describe “Touch and Zap”, an alternative method for whole-cell patch clamp recordings, with the goal of being simpler, quicker and more gentle to brain tissue than previous approaches. Under current clamp mode with a continuous train of hyperpolarizing current pulses, seal formation is initiated immediately upon cell contact, thus the “Touch”. By maintaining the current injection, whole-cell access is spontaneously achieved within seconds from the cell-attached configuration by a self-limited membrane electroporation, or “Zap”, as seal resistance increases. We present examples of intrinsic and visual responses of neurons and putative glial cells obtained with the revised method from cat and rat cortices in vivo. Recording parameters and biophysical properties obtained with the Touch and Zap method compare favourably with those obtained with the traditional blind patch approach, demonstrating that the revised approach does not compromise the recorded cell. We find that the method is particularly well-suited for whole-cell patch recordings of cortical glial cells in vivo, targeting a wider population of this cell type than the standard method, with better access resistance. Overall, the gentler Touch and Zap method is promising for studying quantitative functional properties in the intact brain with minimal perturbation of the cell's intrinsic properties and local network. Because the Touch and Zap method is performed semi-automatically, this approach is more reproducible and less dependent on experimenter technique.

Sensitivity Profile for Orientation Selectivity in the Visual Cortex of Goggle-Reared Mice

It has been widely accepted that ocular dominance in the responses of visual cortical neurons can change depending on visual experience in a postnatal period. However, experience-dependent plasticity for orientation selectivity, which is another important response property of visual cortical neurons, is not yet fully understood. To address this issue, using intrinsic signal imaging and two-photon calcium imaging we attempted to observe the alteration of orientation selectivity in the visual cortex of juvenile and adult mice reared with head-mounted goggles, through which animals can experience only the vertical orientation. After one week of goggle rearing, the density of neurons optimally responding to the exposed orientation increased, while that responding to unexposed orientations decreased. These changes can be interpreted as a reallocation of preferred orientations among visually responsive neurons. Our obtained sensitivity profile for orientation selectivity showed a marked peak at 5 weeks and sustained elevation at 12 weeks and later. These features indicate the existence of a critical period between 4 and 7 weeks and residual orientation plasticity in adult mice. The presence of a dip in the sensitivity profile at 10 weeks suggests that different mechanisms are involved in orientation plasticity in childhood and adulthood.

Rapid Dynamics of Contrast Responses in the Cat Primary Visual Cortex

The visual information we receive during natural vision changes rapidly and continuously. The visual system must adapt to the spatiotemporal contents of the environment in order to efficiently process the dynamic signals. However, neuronal responses to luminance contrast are usually measured using drifting or stationary gratings presented for a prolonged duration. Since motion in our visual field is continuous, the signals received by the visual system contain an abundance of transient components in the contrast domain. Here using a modified reverse correlation method, we studied the properties of responses of neurons in the cat primary visual cortex to different contrasts of grating stimuli presented statically and transiently for 40 ms, and showed that neurons can effectively discriminate the rapidly changing contrasts. The change in the contrast response function (CRF) over time mainly consisted of an increment in contrast gain (CRF shifts to left) in the developing phase of temporal responses and a decrement in response gain (CRF shifts downward) in the decay phase. When the distribution range of stimulus contrasts was increased, neurons demonstrated decrement in contrast gain and response gain. Our results suggest that contrast gain control (contrast adaptation) and response gain control mechanisms are well established during the first tens of milliseconds after stimulus onset and may cooperatively mediate the rapid dynamic responses of visual cortical neurons to the continuously changing contrast. This fast contrast adaptation may play a role in detecting contrast contours in the context of visual scenes that are varying rapidly.

Facilitation of low-frequency stimulation-induced long-term potentiation by endogenous noradrenaline and serotonin in developing rat visual cortex

T-type Ca 2+ channel-dependent long-term potentiation (LTP) occurs predominantly during the critical period of ocular dominance plasticity in rat and cat visual cortex. Noradrenaline and serotonin are known to facilitate ocular dominance plasticity. In this study using rat visual cortical slices, we tested whether this LTP is modulated by these neuromodulators in the same way as ocular dominance plasticity. Extracellular field potentials evoked by layer 4 stimulation were recorded from layer 2/3 and LTP was induced by low-frequency (2 Hz) stimulation continued for 15 min. The induction of LTP was suppressed by β, but not α, adrenergic receptor antagonists. LTP induction was also inhibited by selective antagonists for 5-HT 1A or 5-HT 2 receptors. In slices prepared from rats in which noradrenaline or serotonin was depleted by selective neurotoxins, the magnitude of LTP was significantly smaller compared with control slices. These results indicate that the same types of adrenergic and serotonergic receptors facilitate both LTP and ocular dominance plasticity, supporting our hypothesis that T-type Ca 2+ channel-dependent LTP mediates experience-dependent enhancement of visual responses of cortical neurons during the critical period.

Second-order statistics of natural images

Assuming adaptation of the visual cortex to its environment, we analyze the invariance found in natural images to explain the selective response of visual cortical neurons. We argue that the invariant structure of images can be formally expressed by dot-products. Utilizing the specific structure of the proposed model we show how non-linear functions can be learned efficiently from natural images. In addition to localized edge detectors we found model neurons that respond to changes in texture and cells that detect edge curvature. The analysis suggests new types of features neurons in primary visual cortex may be selective to.

Context-sensitive binding by the laminar circuits of V1 and V2: A unified model of perceptual grouping, attention, and orientation contrast

A detailed neural model is presented of how the laminar circuits of visual cortical areas V1 and V2 implement context-sensitive binding processes such as perceptual grouping and attention. The model proposes how specific laminar circuits allow the responses of visual cortical neurons to be determined not only by the stimuli within their classical receptive fields, but also to be strongly influenced by stimuli in the extra-classical surround. This context-sensitive visual processing can greatly enhance the analysis of visual scenes, especially those containing targets that are low contrast, partially occluded, or crowded by distractors. We show how interactions of feedforward, feedback, and horizontal circuitry can implement several types of contextual processing simultaneously, using shared laminar circuits. In particular, we present computer simulations that suggest how top-down attention and preattentive perceptual grouping, two processes that are fundamental for visual binding, can interact, with attentional enhancement selectively propagating along groupings of both real and illusory contours, thereby showing how attention can selectively enhance object representations. These simulations also illustrate how attention may have a stronger facilitatory effect on low contrast than on high contrast stimuli, and how pop-out from orientation contrast may occur. The specific functional roles which the model proposes for the cortical layers allow several testable neurophysiological predictions to be made. The results presented here simulate only the boundary grouping system of adult cortical architecture. However, we also discuss how this model contributes to a larger neural theory of vision that suggests how intracortical and intercortical feedback help to stabilize development and learning within these cortical circuits. Although feedback plays a key role, fast feedforward processing is possible in response to unambiguous information. Model circuits are capable of synchronizing quickly, but context-sensitive persistence of previous events can influence how synchrony develops. Although these results focus on how the interblob cortical processing stream controls boundary grouping and attention, related modelling of the blob cortical processing stream suggests how visible surfaces are formed, and modelling of the motion stream suggests how transient responses to scenic changes can control long-range apparent motion and also attract spatial attention.

Chapter 13 The role of feedback connections in shaping the responses of visual cortical neurons

The results of a previous study [Hupé et al. (1998) Nature, 394: 784-787] led us to conclude that feedback connections are important for differentiating a figure from the background, particularly in the case of low salience stimuli. This conclusion was principally based on the observation in area V3 neurons that inactivating MT by cooling led to a severe weakening of the center response and of the center-surround interactions, and that these effects were particularly strong for low salience stimuli. In the present paper, we first show that the results extend to areas V1 and V2. In particular, the inhibitory center-surround interactions in areas V1, V2 and V3 disappear almost completely in the absence of feedback input from MT for low salience stimuli, whereas the effects are much more limited for stimuli of middle and high salience. We then compare the results obtained in studies of feedback connections from MT to those obtained in a study of the feedback action of area V2 onto V1 neurons [Hupé et al. (2001) J. Neurophysiol., 85: 146-163], in which the same effects were observed on the center mechanism (decrease in response), but no effects were seen on the center-surround interactions. We conclude that feedback connections act in a non-linear fashion to boost the gain of the center mechanism and that they combine with horizontal connections to generate the center-surround interactions.

The influence of threshold variability on the response of visual cortical neurons

Orientation–selective neurons in monkeys and cats show contrast saturation and contrast-invariant orientation tuning (Albrecht and Hamilton, J. Neurophysiol. 48 (1982) 217–237). Recently proposed models for orientation selectivity predict contrast invariant orientation tuning but no contrast saturation at high strength of intracortical recurrent couplings, whereas at lower coupling strengths the contrast response saturates but the tuning widths are contrast dependent (Hansel and Sompolinsky, Methods in Neuronal Modeling, MIT Press, Cambridge, MA, 1997, pp. 499–567; Stetter et al., Visual Neurosci., Submitted for publication). In the present work we address the question, if and under which conditions the incorporation of a stochastic distribution of activation thresholds for cortical neurons helps resolving that paradoxon. We find that both phenomena occurs naturally if two different classes of inhibitory inter-neurons are combined. Low-threshold inhibition keeps the gain of the cortical amplification finite, whereas high-threshold inhibition causes contrast saturation.