Search

Visually evoked activity is necessary for the normal development of the visual system. However, little is known about the capacity for patterned spontaneous activity to drive the maturation of receptive fields before visual experience. Retinal waves provide instructive retinotopic information for the anatomical organization of the visual thalamus. To determine whether retinal waves also drive the maturation of functional responses, we increased the frequency of retinal waves pharmacologically in the ferret (Mustela putorius furo) during a period of retinogeniculate development before eye opening. The development of geniculate receptive fields after receiving these increased neural activities was measured using single-unit electrophysiology. We found that increased retinal waves accelerate the developmental reduction of geniculate receptive field sizes. This reduction is due to a decrease in receptive field center size rather than an increase in inhibitory surround strength. This work reveals an instructive role for patterned spontaneous activity in guiding the functional development of neural circuits. [ABSTRACT FROM AUTHOR]

The fovea dominates primate vision, and its anatomy and perceptual abilities are well studied, but its physiology has been little explored because of limitations of current physiological methods. In this study, we adapted a novel in vivo imaging method, originally developed in mouse retina, to explore foveal physiology in the macaque, which permits the repeated imaging of the functional response of many retinal ganglion cells (RGCs) simultaneously. A genetically encoded calcium indicator, G-CaMP5, was inserted into foveal RGCs, followed by calcium imaging of the displacement of foveal RGCs from their receptive fields, and their intensity-response functions. The spatial offset of foveal RGCs from their cone inputs makes this method especially appropriate for fovea by permitting imaging of RGC responses without excessive light adaptation of cones. This new method will permit the tracking of visual development, progression of retinal disease, or therapeutic interventions, such as insertion of visual prostheses. [ABSTRACT FROM AUTHOR]

The responses of neurons within posterior visual cortex are enhanced when response field (RF) stimuli are targeted with saccadic eye movements. Although the motor-related activity within oculomotor structures seems a likely source of the enhancement, the origin of the modulation is unknown. Wetested the role of the frontal eye field (FEF) in driving presaccadic modulation in area V4 by inactivating FEF neurons at retinotopically corresponding sites within the macaque monkey (Macaca mulatta) brain. As previously observed, FEF inactivation produced profound, and spatially specific, deficits in memory-guided saccades, and increased the latency, scatter, and duration of visually guided saccades. Despite the clear behavioral deficits, we found that rather than being eliminated or reduced by FEF inactivation, presaccadic enhancement of V4 activity was increased. FEF inactivation nonetheless diminished the stimulus discriminability of V4 visual responses both during fixation and in the presaccadic period. Thus, without input from the FEF, V4 neurons signaled more about the direction of saccades and less about the features of the saccadic target. In addition, FEF inactivation significantly increased the suppressive effects of non-RF stimuli on V4 activity. These results reveal multiple sources of presaccadic modulation in V4 and suggest that the FEF contributes uniquely to the presaccadic specification of visual target features. [ABSTRACT FROM AUTHOR]

In the early stages of image analysis, visual cortex represents scenes as spatially organized maps of locally defined features (e.g., edge orientation). As image reconstruction unfolds and features are assembled into larger constructs, cortex attempts to recover semantic content for object recognition. It is conceivable that higher level representations may feed back onto early processes and retune their properties to align with the semantic structure projected by the scene; however, there is no clear evidence to either support or discard the applicability of this notion to the human visual system. Obtaining such evidence is challenging because low and higher level processes must be probed simultaneously within the same experimental paradigm. We developed a methodology that targets both levels of analysis by embedding low-level probes within natural scenes. Human observers were required to discriminate probe orientation while semantic interpretation of the scene was selectively disrupted via stimulus inversion or reversed playback. We characterized the orientation tuning properties of the perceptual process supporting probe discrimination; tuning was substantially reshaped by semantic manipulation, demonstrating that low-level feature detectors operate under partial control from higher level modules. The manner in which such control was exerted may be interpreted as a top-down predictive strategy whereby global semantic content guides and refines local image reconstruction. We exploit the novel information gained from data to develop mechanistic accounts of unexplained phenomena such as the classic face inversion effect. [ABSTRACT FROM AUTHOR]

Visual systems extract directional motion information from spatiotemporal luminance changes on the retina. An algorithmic model, the Reichardt detector, accounts for this by multiplying adjacent inputs after asymmetric temporal filtering. The outputs of two mirror-symmetrical units tuned to opposite directions are thought to be subtracted on the dendrites of wide-field motion-sensitive lobula plate tangential cells by antagonistic transmitter systems. In Drosophila, small-field T4/T5 cells carry visual motion information to the tangential cells that are depolarized during preferred and hyperpolarized during null direction motion. While preferred direction input is likely provided by excitation from T4/T5 terminals, the origin of null direction inhibition is unclear. Probing the connectivity between T4/T5 and tangential cells in Drosophila using a combination of optogenetics, electrophysiology, and pharmacology, we found a direct excitatory as well as an indirect inhibitory component. This suggests that the null direction response is caused by feedforward inhibition via yet unidentified neurons. [ABSTRACT FROM AUTHOR]

In the developing mouse retina, spontaneous and light-driven activity shapes bipolar 3ganglion cell glutamatergic synapse formation, beginning around the time of eye-opening (P12-P14) and extending through the first postnatal month. During this time, glutamate release can spill outside the synaptic cleft and possibly stimulate extrasynaptic NMDA-type glutamate receptors (NMDARs) on ganglion cells. Furthermore, the role of NMDARs during development may differ between ON and OFF bipolar synapses as in mature retina, where ON synapses reportedly include extrasynaptic NMDARs with GluN2B subunits. To better understand the function of glutamatergic synapses during development, we made whole-cell recordings of NMDAR-mediated responses, in vitro, from two types of genetically identified direction-selective ganglion cells (dsGCs): TRHR (thyrotropin-releasing hormone receptor) and Drd4 (dopamine receptor 4). Both dsGC types responded to puffed NMDA between P7 and P28; and both types exhibited robust light-evoked NMDAR-mediated responses at P14 and P28 that were quantified by conductance analysis during nicotinic and GABAA receptor blockade. For a given cell type and at a given age, ON and OFF bipolar cell inputs evoked similar NMDAR-mediated responses, suggesting that ON-versus-OFF differences in mature retina do not apply to the cell types or ages studied here. At P14, puff- and light-evoked NMDAR-mediated responses in both dsGCs were partially blocked by the GluN2B antagonist ifenprodil, whereas at P28 only TRHR cells remained ifenprodilsensitive. NMDARs contribute at both ON and OFF bipolar cell synapses during a period of robust activity-dependent synaptic development, with declining GluN2B involvement over time in specific ganglion cell types. [ABSTRACT FROM AUTHOR]

Many forms of learning require temporally ordered stimuli. In Pavlovian eyeblink conditioning, a conditioned stimulus (CS) must precede the unconditioned stimulus (US) by at least about 100 ms for learning to occur. Conditioned responses are learned and generated by the cerebellum. Recordings from the cerebellar cortex during conditioning have revealed CS-triggered pauses in the firing of Purkinje cells that likely drive the conditioned blinks. The predominant view of the learning mechanism in conditioning is that long-term depres-sion (LTD) at parallel fiber (PF)-Purkinje cell synapses underlies the Purkinje cell pauses. This raises a serious conceptual challenge because LTD is most effectively induced at short CS-US intervals, which do not support acquisition of eyeblinks. To resolve this discrep-ancy, we recorded Purkinje cells during conditioning with short or long CS-US intervals. Decerebrated ferrets trained with CS-US intervals ≥150 ms reliably developed Purkinje cell pauses, but training with an interval of 50 ms unexpectedly induced increases in CS-evoked spiking. This bidirectional modulation of Purkinje cell activity offers a basis for the requirement of a minimum CS-US interval for conditioning, but we argue that it cannot be fully explained by LTD, even when previous in vitro studies of stimulus-timing-dependent LTD are taken into account. [ABSTRACT FROM AUTHOR]

To encode binocular disparity, the visual system determines the image patches in one eye that yield the highest correlation with patches in the other eye. The computation of interocular correlation occurs after spatiotemporal filtering of monocular signals, which leads to restrictions on disparity variations that can support depth perception. We quantified those restrictions by measuring humans' ability to see disparity variation at a wide range of spatial and temporal frequencies. Lower-disparity thresholds cut off at very low spatiotemporal frequencies, which is consistent with the behavior of V1 neurons. Those thresholds are space-time separable, suggesting that the underlying neural mechanisms are separable. We also found that upper-disparity limits were characterized by a spatiotemporal, disparity-gradient limit; to be visible, disparity variation cannot exceed a fixed amount for a given interval in space-time. Our results illustrate that the disparity variations that humans can see are very restricted compared with the corresponding luminance variations. The results also provide insight into the neural mechanisms underlying depth from disparity, such as why stimuli with long interocular delays can still yield clear depth percepts. [ABSTRACT FROM AUTHOR]

Thecommonmarmoset (Callithrix jacchus), a small-bodiedNewWorld primate, offers several advantages to complement vision research in larger primates. Studies in the anesthetized marmoset have detailed the anatomy and physiology of their visual system (Rosa et al., 2009) while studies of auditory and vocal processing have established their utility for awake and behaving neurophysiological investigations (Lu et al., 2001a,b; Eliades and Wang, 2008a,b; Osmanski and Wang, 2011; Remington et al., 2012). However, a critical unknown is whether marmosets can perform visual tasks under head restraint. This has been essential for studies in macaques, enabling both accurate eye tracking and head stabilization for neurophysiology. In one set of experiments we compared the free viewing behavior of head-fixed marmosets to that of macaques, and found that their saccadic behavior is comparable across a number of saccade metrics and that saccades target similar regions of interest including faces. In a second set of experiments we applied behavioral conditioning techniques to determine whether the marmoset could control fixation for liquid reward. Two marmosets could fixate a central point and ignore peripheral flashing stimuli, as needed for receptive field mapping. Both marmosets also performed an orientation discrimination task, exhibiting a saturating psychometric function with reliable performance and shorter reaction times for easier discriminations. These data suggest that the marmoset is a viable model for studies of active vision and its underlying neural mechanisms. [ABSTRACT FROM AUTHOR]

The elongation rate of axons is tightly regulated during development. Recycling of the plasma membrane is known to regulate axon extension; however, the specific molecules involved in recycling within the growth cone have not been fully characterized. Here, we investigated whether the small GTPases Rab4 and Rab5 involved in short-loop recycling regulate the extension of Xenopus retinal axons. We report that, in growth cones, Rab5 and Rab4 proteins localize to endosomes, which accumulate markers that are constitutively recycled. Fluorescence recovery after photo-bleaching experiments showed that Rab5 and Rab4 are recruited to endosomes in the growth cone, suggesting that they control recycling locally. Dynamic image analysis revealed that Rab4-positive carriers can bud off from Rab5 endosomes and move to the periphery of the growth cone, suggesting that both Rab5 and Rab4 contribute to recycling within the growth cone. Inhibition of Rab4 function with dominant-negative Rab4 or Rab4 morpholino and constitutive activation of Rab5 decreases the elongation of retinal axons in vitro and in vivo, but, unexpectedly, does not disrupt axon pathfinding. Thus, Rab5- and Rab4-mediated control of endosome trafficking appears to be crucial for axon growth. Collectively, our results suggest that recycling from Rab5-positive endosomes via Rab4 occurs within the growth cone and thereby supports axon elongation. [ABSTRACT FROM AUTHOR]

Reference frames are important for understanding sensory processing in the cortex. Previous work showed that vestibular heading signals in the ventral intraparietal area (VIP) are represented in body-centered coordinates. In contrast, vestibular heading tuning in the medial superior temporal area (MSTd) is approximately head centered. We considered the hypothesis that visual heading signals (from optic flow) in VIP might also be transformed into a body-centered representation, unlike visual heading tuning in MSTd, which is approximately eye centered. We distinguished among eye-centered, head-centered, and body-centered spatial reference frames by systematically varying both eye and head positions while rhesus monkeys viewed optic flow stimuli depicting various headings. We found that heading tuning of VIP neurons based on optic flow generally shifted with eye position, indicating an eye-centered spatial reference frame. This is similar to the representation of visual heading signals in MSTd, but contrasts sharply with the body-centered representation of vestibular heading signals in VIP. These findings demonstrate a clear dissociation between the spatial reference frames of visual and vestibular signals in VIP, and emphasize that frames of reference for neurons in parietal cortex can depend on the type of sensory stimulation. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that strong neural modulations can be evoked with optogenetic stimulation in macaque motor cortex without observing any evoked movements (Han et al., 2009, 2011; Diester et al., 2011). It remains unclear why such perturbations do not generate movements and if conditions exist under which they may evoke movements. In this study, we examine the effects of five optogenetic constructs in the macaque frontal eye field and use electrical microstimulation to assess whether optical perturbation of the local network leads to observable motor changes during optical, electrical, and combined stimulation. We report a significant increase in the probability of evoking saccadic eye movements when low current electrical stimulation is coupled to optical stimulation compared with when electrical stimulation is used alone. Experiments combining channelrhodopsin 2 (ChR2) and electrical stimulation with simultaneous fMRI revealed no discernible fMRI activity at the electrode tip with optical stimulation but strong activity with electrical stimulation. Our findings suggest that stimulation with current ChR2 optogenetic constructs generates subthreshold activity that contributes to the initiation of movements but, in most cases, is not sufficient to evoke a motor response. [ABSTRACT FROM AUTHOR]

In both vertebrates and invertebrates, evidence supports separation of luminance increments and decrements (ON and OFF channels) in early stages of visual processing (Hartline, 1938; Joesch et al., 2010); however, less is known about how these parallel pathways are recombined to encode form and motion. In Drosophila, genetic knockdown of inputs to putative ON and OFF pathways and direct recording from downstream neurons in the wide-field motion pathway reveal that local elementary motion detectors exist in pairs that separately correlate contrast polarity channels, ON with ON and OFF with OFF (Joesch et al., 2013). However, behavioral responses to reverse-phi motion of discrete features reveal additional correlations of the opposite signs (Clark et al., 2011). We here present intracellular recordings from feature detecting neurons in the dragonfly that provide direct physiological evidence for the correlation of OFF and ON pathways. These neurons show clear polarity selectivity for feature contrast, responding strongly to targets that are darker than the background and only weakly to dark contrasting edges. These dark target responses are much stronger than the linear combination of responses to ON and OFF edges. We compare these data with output from elementary motion detector-based models (Eichner et al., 2011; Clark et al., 2011), with and without stages of strong center-surround antago-nism. Our data support an alternative elementary small target motion detector model, which derives dark target selectivity from the correlation of a delayed OFF with an un-delayed ON signal at each individual visual processing unit (Wiederman et al., 2008,2009). [ABSTRACT FROM AUTHOR]

A salient visual stimulus can be rendered invisible by presenting it to one eye while flashing a mask to the other eye. This procedure, called continuous flash suppression (CFS), has been proposed as an ideal way of studying awareness as it can make a stimulus imperceptible for extended periods of time. Previous studies have reported robust suppression of cortical activity in higher visual areas during CFS, but the role of primary visual cortex (VI) is still controversial. In this study, we resolve this controversy on the role of VI in CFS and also begin characterizing the computational processes underlying CFS. Early visual cortical activity was measured with functional magnetic resonance imaging while human subjects viewed stimuli composed of target and mask, presented to the same or different eyes. Functional MRI responses in early visual cortex were smaller when target and mask were in different eyes compared with the same eye, not only for the lowest contrast target rendered invisible by CFS, but also for higher contrast targets, which were visible even when presented to the eye opposite the mask. We infer that CFS is based on modulating the gain of neural responses, akin to reducing target contrast. [ABSTRACT FROM AUTHOR]

Neurons at the top of primate ventral visual stream [inferior temporal cortex (IT)] have selectivity for objects that is highly tolerant to variation in the object's appearance on the retina. Previous nonhuman primate (Macaca mulatta) studies suggest that this neuronal tolerance is at least partly supported by the natural temporal contiguity of visual experience, because altering that temporal contiguity can robustly alter adult IT position and size tolerance. According to that work, it is the statistics of the subject's visual experience, not the subject's reward, that instruct the specific images that IT treats as equivalent. But is reward necessary for gating this type of learning in the ventral stream? Here we show that this is not the case--temporal tolerance learning proceeds at the same rate, regardless of reward magnitude and regardless of the temporal co-occurrence of reward, even in a behavioral task that does not require the subject to engage the object images. This suggests that the ventral visual stream uses autonomous, fully unsupervised mechanisms to constantly leverage all visual experience to help build its invariant object representation. [ABSTRACT FROM AUTHOR]

Studying the insect visual system provides important data on the basic neural mechanisms underlying visual processing. As in vertebrates, the first step in visual processing in insects is through a series of retinotopic neurons. Recent studies on flies have found that these converge onto assemblies of columnar neurons in the lobula, the axons of which segregate to project to discrete optic glomeruli in the lateral protocerebrum. This arrangement is much like the fly's olfactory system, in which afferents target uniquely identifiable olfactory glomeruli. Here, whole-cell patch recordingsshowthat eventhoughvisual primitives are unreliablyencodedbysingle lobula outputneuronsbecause of high synaptic noise, they are reliably encoded by the ensemble of outputs. At a glomerulus, local interneurons reliably code visual primitives, as do projection neurons conveying information centrally from the glomerulus. These observations demonstrate that in Drosophila, as in other dipterans, optic glomeruli are involved in further reconstructing the fly's visual world. Optic glomeruli and antennal lobe glomeruli share the same ancestral anatomical and functional ground pattern, enabling reliable responses to be extracted from converging sensory inputs. [ABSTRACT FROM AUTHOR]

In natural images, visual objects are typically occluded by other objects. Are markable ability of our visual system is to complete occluded objects effortlessly and see whole, uninterrupted objects. How object completion is implemented in the visual system is still largely unknown. In this study, using a backward masking paradigm, we combined psychophysics and functional magnetic resonance imaging to investigate the temporal evolvement of face completion at different levels of the visual processing hierarchy. Human subjects were presented with two kinds of stimuli that were designed to elicit or not elicit the percept of a completed face, although they were physically very similar. By contrasting subjects' behavioral and blood oxygenation level-dependent (BOLD) responses to completed and noncompleted faces, we measured the psychophysical time course of the face completion and its underlying cortical dynamics. We found that face completion manifested its effect between 50 and 250 ms after stimulus onset. Relative to noncompleted faces, completed faces induced weaker BOLD response at early processing phases in retinotopic visual areas V1 and V2 and stronger BOLD response at late processing phases in occipital face area and fusiform face area. Attending away from the stimuli largely abolished these effects. These findings suggest that face completion consists of two synergetic phases: early suppression in lower visual areas and late enhancement in higher visual areas; moreover, attention is necessary to these neural events. [ABSTRACT FROM AUTHOR]

The primate superior colliculus (SC) is often viewed as composed of two distinct motor zones with complementary functions: a peripheral region that helps generate saccades to eccentric targets and a central one that maintains fixation by suppressing saccades. Here, we directly tested the alternative interpretation that topography in the SC is not strictly motor, nor does it form two distinct zones, but instead forms a single map of behaviorally relevant goal locations. Primates tracked the invisible midpoint between two moving stimuli, such that the stimuli guiding tracking were peripheral whereas the inferred movement goal was foveal and parafoveal. Temporary inactivation of neurons in the central portion of the topographic map of the SC, representing the invisible goal, caused stable offsets in eye position during tracking that were directed away from the retinotopic position encoded by the inactivated SC site. Critically, these offsets were not accompanied by a systematic inability to generate or suppress saccades, and they were not fully explained by motor deficits in saccades, smooth pursuit, or fixation. In addition, the magnitude of the offset depended on the eccentricity of the inactivated site as well as the degree of spatial uncertainty associated with the behavioral goal. These results indicate that gaze control depends on the balance of activity across a map of goal locations in the SC, and that by silencing some of the neurons in the normally active population representing the behavioral goal, focal inactivation causes a biased estimate of where to look. [ABSTRACT FROM AUTHOR]