Responses In Superior Colliculus Research Articles

Neural substrates for saccadic modulation of visual representations in mouse superior colliculus.

How do sensory systems account for stimuli generated by natural behavior? We addressed this question by examining how an ethologically relevant class of saccades modulates visual representations in the mouse superior colliculus (SC), a key region for sensorimotor integration. We quantified saccadic modulation by recording SC responses to visual probes presented at stochastic saccade-probe latencies. Saccades significantly impacted population representations of the probes, with early enhancement that began prior to saccades and pronounced suppression for several hundred milliseconds following saccades, independent of units' visual response properties or directional tuning. To determine the cause of saccadic modulation, we presented fictive saccades that simulated the visual experience during saccades without motor output. Some units exhibited similar modulation by fictive and real saccades, suggesting a sensory-driven origin of saccadic modulation, while others had dissimilar modulation, indicating a motor contribution. These findings advance our understanding of the neural basis of natural visual coding.

Short-latency preference for faces in primate superior colliculus depends on visual cortex

Face processing is fundamental to primates and has been extensively studied in higher-order visual cortex. Here, we report that visual neurons in the midbrain superior colliculus (SC) of macaque monkeys display a preference for images of faces. This preference emerges within 40ms of stimulus onset-well before "face patches" in visual cortex-and, at the population level, can be used to distinguish faces from other visual objects with accuracies of ∼80%. This short-latency face preference in SC depends on signals routed through early visual cortex because inactivating the lateral geniculate nucleus, the key relay from retina to cortex, virtually eliminates visual responses in SC, including face-related activity. These results reveal an unexpected circuit in the primate visual system for rapidly detecting faces in the periphery, complementing the higher-order areas needed for recognizing individual faces.

Human subcortical pathways automatically detect collision trajectory without attention and awareness.

Detecting imminent collisions is essential for survival. Here, we used high-resolution fMRI at 7 Tesla to investigate the role of attention and consciousness for detecting collision trajectory in human subcortical pathways. Healthy participants can precisely discriminate collision from near-miss trajectory of an approaching object, with pupil size change reflecting collision sensitivity. Subcortical pathways from the superior colliculus (SC) to the ventromedial pulvinar (vmPul) and ventral tegmental area (VTA) exhibited collision-sensitive responses even when participants were not paying attention to the looming stimuli. For hemianopic patients with unilateral lesions of the geniculostriate pathway, the ipsilesional SC and VTA showed significant activation to collision stimuli in their scotoma. Furthermore, stronger SC responses predicted better behavioral performance in collision detection even in the absence of awareness. Therefore, human tectofugal pathways could automatically detect collision trajectories without the observers' attention to and awareness of looming stimuli, supporting "blindsight" detection of impending visual threats.

Distinct circuits in anterior cingulate cortex encode safety assessment and mediate flexibility of fear reactions

Safety assessment and threat evaluation are crucial for animals to live and survive in the wilderness. However, neural circuits underlying safety assessment and their transformation to mediate flexibility of fear-induced defensive behaviors remain largely unknown. Here, we report that distinct neuronal populations in mouse anterior cingulate cortex (ACC) encode safety status by selectively responding under different contexts of auditory threats, with one preferably activated when an animal staysing in a self-deemed safe zone and another specifically activated in more dangerous environmental settings that led to escape behavior. The safety-responding neurons preferentially target the zona incerta (ZI), which suppresses the superior colliculus (SC) via its GABAergic projection, while the danger-responding neurons preferentially target and excite SC. These distinct corticofugal pathways antagonistically modulate SC responses to threat, resulting in context-dependent expression of fear reactions. Thus, ACC serves as a critical node to encode safety/danger assessment and mediate behavioral flexibility through differential top-down circuits.

Noise-rearing precludes the behavioral benefits of multisensory integration.

Concordant visual-auditory stimuli enhance the responses of individual superior colliculus (SC) neurons. This neuronal capacity for "multisensory integration" is not innate: it is acquired only after substantial cross-modal (e.g. auditory-visual) experience.Masking transient auditory cues by raising animals inomnidirectional sound ("noise-rearing") precludes their ability to obtain this experience and the ability of the SC to construct a normal multisensory (auditory-visual) transform. SC responses to combinations of concordant visual-auditory stimuli are depressed, rather than enhanced. The present experiments examined the behavioral consequence of this rearing condition in a simple detection/localization task. In the first experiment, the auditory component of the concordant cross-modal pair was novel, and only the visual stimulus was a target. In the second experiment, both component stimuli were targets. Noise-reared animals failed to show multisensory performance benefits in either experiment. These results reveal a close parallel between behavior and single neuron physiology in the multisensory deficits that are induced when noise disrupts early visual-auditory experience.

Visual Dysfunction of the Superior Colliculus in De Novo Parkinsonian Patients.

The dual hit hypothesis about the pathogenesis of Parkinson disease (PD) suggests that the brainstem is a convergent area for the propagation of pathological α-synuclein from the periphery to the brain. Although brainstem structures are likely to be affected early in the course of the disease, detailed information regarding specific brainstem regions is lacking. The aim of our study was to investigate the function of the superior colliculus, a sensorimotor brainstem structure, in de novo PD patients compared to controls using brain functional magnetic imaging and visual stimulation paradigms. De novo PD patients and controls were recruited. PD subjects were imaged before and after starting PD medications. A recently developed functional magnetic resonance imaging protocol was used to stimulate and visualize the superior colliculus and 2 other visual structures: the lateral geniculate nucleus and the primary visual cortex. In the 22 PD patients, there was no modulation of the superior colliculus responses to the luminance contrasts compared to controls. This implies a hypersensitivity to low luminance contrast and abnormal rapid blood oxygenation level-dependent signal saturation to high luminance contrasts. The lateral geniculate nucleus was only modulated by 3 to 9% luminance contrasts compared to controls. No major differences were found in the primary visual cortex between both groups. Our findings suggest that pathological superior colliculus visual responses in de novo PD patients are present early in the course of the disease. Changes in imaging the superior colliculus could play an important role as a preclinical biomarker of the disease. ANN NEUROL 2020;87:533-546.

Differential sensitivity of the On and Off visual responses to retinal ischemia

Retinal ischemia is a common condition that may lead into vision impairment and blindness. In this study, we evaluated changes separately in On and Off visual responses induced by retinal ischemia. To do this, reversible retinal ischemia was induced in anaesthetized rats by increasing the intraocular pressure until the eye fundus became whitish for either 30 or 60 min. Both electroretinogram (ERG) and multiunit neuronal activity in the superior colliculus (SC) were recorded simultaneously for at least 20 min before, during, and after ischemia. In addition, in normal eyes, intravitreal glycine (Gly) injections were performed to further investigate the mechanisms involved in this process. We found that collicular Off responses were more sensitive to ischemia than On responses. The Off response was the first one to decay at the time ischemia was induced and the last to recover after blood reperfusion. The duration of ischemia also differentially affected both responses. After 30 min of ischemia, 14% of SC recordings failed to recover Off responses. After 1 h of ischemia, the percentage of recordings that failed to recover Off responses increased to 50%. Post-ischemic ERGs remained unaltered in all cases. Intravitreal Gly injections caused suppression of Off responses in the SC. Higher doses caused suppression of both On and Off responses in the SC but with no effect on the ERG at the doses tested. In summary, Off responses were more sensitive than On responses to ischemia suggesting that different mechanisms drive the two types of responses. The recovery of transitory ischemia was not complete in the SC responses whereas the ERG remained unaltered, suggesting that retinal damage produced by ischemia is more prominent in ganglion cells. Our results provide critical information for understanding ischemia repercussions and visual processing in the early visual system.

The Superior Colliculus in De Novo Parkinson's Disease: A Prodromal Dysfunction?

Background: The dual hit hypothesis about the pathogenesis of Parkinson's disease (PD) suggests that the brainstem can convey pathological entries to the brain. However, information about the involvement of different brainstem structures are difficult to collect in living PD patients. We have filled this gap by studying with functional brain MRI the superior colliculus (SC), a brainstem sensorimotor structure. Starting with the discovery that the SC shows abnormal visual responses in PD rat models, we aimed at studying the SC also in de novo PD patients. Methods: De novo PD patients and controls were studied using a recently developed fMRI protocol to stimulate and visualize the SC, the lateral geniculate nucleus (LGN) and the primary visual cortex (V1). The visual responses modulation of these structures was studied using luminance contrasts from 1% to 9%. We compared SC, LGN, and V1 BOLD responses of de novo PD patients with matching controls. The effects of dopaminergic treatment in PD patients were further evaluated. Findings: In the 22 enrolled PD patients, there was no modulation of the SC responses to the luminance contrasts, and the LGN was only modulated by 3%-9% luminance contrasts compared to the 22 controls. No major differences were found in V1 between both groups. Moreover, SC lack of modulation was more frequent in less affected de novo PD patients (Hoehn & Yahr stage 1). Dopaminergic treatment had no effect on SC and LGN modulation. Interpretation: De novo PD patients showed pathological responses to the luminance contrasts in the SC, suggesting that SC dysfunction could be diagnostic of PD. Since the SC seems to be more affected at stage 1 of PD, its dysfunction might be detected even earlier, supporting its potential role as a prodromal biomarker of PD. Clinical Trial Number: ClinicalTrial.gov (NCT02488395). Funding Statement: The work was funded by the University Grenoble Alpes, “La Fondation de l’Avenir” and “France Parkinson”. The Grenoble MRI facility IRMaGe was partly funded by the French program ‘Investissement d’Avenir” run by the Agence Nationale pour la Recherche (ANR-11-INBS-0006). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: All participants provided written informed consent to the study. The study was approved by the local ethical committee (ID RCB- 2014-A01835-42).

Auditory-visual convergence at the superior colliculus in rat using functional MRI.

The superior colliculus (SC) of the midbrain has been a model structure for multisensory processing. Many neurons in the intermediate and deep SC layers respond to two or more of auditory, visual, and somatosensory stimuli as assessed by electrophysiology. In contrast, noninvasive and large field of view functional magnetic resonance imaging (fMRI) studies have focused on multisensory processing in the cortex. In this study, we applied blood oxygenation leveldependent (BOLD) fMRI on Sprague-Dawley rats receiving monaural (auditory) and binocular (visual) stimuli to study subcortical multisensory processing. Activation was observed in the left superior olivary complex, lateral lemniscus, and inferior colliculus and both hemispheres of the superior colliculus during auditory stimulation. The SC response was bilateral even though the stimulus was monaural. During visual stimulation, activation was observed in both hemispheres of the SC and lateral geniculate nucleus. In both hemispheres of the SC, the number of voxels in the activation area $( \mathrm {p}<10 -8$) and BOLD signal changes $( \mathrm {p}<0.01)$ were significantly greater during visual than auditory stimulation. These results provide functional imaging evidence that the SC is a site of auditoryvisual convergence due to its involvement in both auditory and visual processing. The auditory and visual fMRI activations likely reflect the firing of unisensory and multisensory neurons in the SC. The present study lays the groundwork for noninvasive functional imaging studies of multisensory convergence and integration in the SC.

Sheets of human retinal progenitor transplants improve vision in rats with severe retinal degeneration

Loss of photoreceptors and other retinal cells is a common endpoint in retinal degenerate (RD) diseases that cause blindness. Retinal transplantation is a potential therapy to replace damaged retinal cells and improve vision. In this study, we examined the development of human fetal retinal sheets with or without their retinal pigment epithelium (RPE) transplanted to immunodeficient retinal degenerate rho S334ter-3 rats. Sheets were dissected from fetal human eyes (11–15.7 weeks gestation) and then transplanted to the subretinal space of 24–31 d old RD nude rats. Every month post surgery, eyes were imaged by high-resolution spectral-domain optical coherence tomography (SD-OCT). SD-OCT showed that transplants were placed into the subretinal space and developed laminated areas or rosettes, with clear development of plexiform layers first seen in OCT at 3 months post surgery. Several months later, as could be expected by the much slower development of human cells compared to rat cells, transplant photoreceptors developed inner and later outer segments. Retinal sections were analyzed by immunohistochemistry for human and retinal markers and confirmed the formation of several retinal subtypes within the retinal layers. Transplant cells extended processes and a lot of the cells could also be seen migrating into the host retina. At 5.8–8.6 months post surgery, selected rats were exposed to light flashes and recorded for visual responses in superior colliculus, (visual center in midbrain). Four of seven rats with transplants showed responses to flashes of light in a limited area of superior colliculus. No response with the same dim light intensity was found in age-matched RD controls (non-surgery or sham surgery). In summary, our data showed that human fetal retinal sheets transplanted to the severely disturbed subretinal space of RD nude rats develop mature photoreceptors and other retinal cells, integrate with the host and induce vision improvement.

Gamma oscillations in the superior colliculus and pulvinar in response to faces support discrimination performance in monkeys

The subcortical visual pathway including the superior colliculus (SC), pulvinar, and amygdala has been implicated in unconscious visual processing of faces, eyes, and gaze direction in blindsight. Our previous studies reported that monkey SC and pulvinar neurons responded preferentially to images of faces while performing a delayed non-matching to sample (DNMS) task to discriminate different visual stimuli (Nguyen et al., 2013, 2014). However, the contribution of SC and pulvinar neurons to the discrimination of the facial images and subsequent behavioral performance remains unknown. Since gamma oscillations have been implicated in sensory and cognitive processes as well as behavioral execution, we hypothesized that gamma oscillations during neuronal responses might contribute to achieving the appropriate behavioral performance (i.e., a correct response). In the present study, we re-analyzed those neuronal responses in the monkey SC and pulvinar to investigate possible relationships between gamma oscillations in these neurons and behavioral performance (correct response ratios) during the DNMS task. Gamma oscillations of SC and pulvinar neuronal activity were analyzed in three phases around the stimulus onset [inter-trial interval (ITI): 1000ms before trial onset; Early: 0–200ms after stimulus onset; and Late: 300–500ms after stimulus onset]. We found that human facial images elicited stronger gamma oscillations in the early phase than the ITI and late phase in both the SC and pulvinar neurons. Furthermore, there was a significant correlation between strengths of gamma oscillations in the early phase and behavioral performance in both the SC and pulvinar. The results suggest that gamma oscillatory activity in the SC and pulvinar contributes to successful behavioral performance during unconscious perceptual and behavioral processes.

Commentary: Express saccades and superior colliculus responses are sensitive to short-wavelength cone contrast.

Commentary: Express saccades and superior colliculus responses are sensitive to short-wavelength cone contrast.

3D functional ultrasound imaging of the cerebral visual system in rodents

3D functional imaging of the whole brain activity during visual task is a challenging task in rodents due to the complex tri-dimensional shape of involved brain regions and the fine spatial and temporal resolutions required to reveal the visual tract. By coupling functional ultrasound (fUS) imaging with a translational motorized stage and an episodic visual stimulation device, we managed to accurately map and to recover the activity of the visual cortices, the Superior Colliculus (SC) and the Lateral Geniculate Nuclei (LGN) in 3D. Cerebral Blood Volume (CBV) responses during visual stimuli were found to be highly correlated with the visual stimulus time profile in visual cortices (r=0.6), SC (r=0.7) and LGN (r=0.7). These responses were found dependent on flickering frequency and contrast, and optimal stimulus parameters for largest CBV increases were obtained. In particular, increasing the flickering frequency higher than 7Hz revealed a decrease of visual cortices response while the SC response was preserved. Finally, cross-correlation between CBV signals exhibited significant delays (d=0.35s +/−0.1s) between blood volume response in SC and visual cortices in response to our visual stimulus. These results emphasize the interest of fUS imaging as a whole brain neuroimaging modality for brain vision studies in rodent models.

Vision Recovery and Connectivity by Fetal Retinal Sheet Transplantation in an Immunodeficient Retinal Degenerate Rat Model.

PurposeTo characterize a recently developed model, the retinal degenerate immunodeficient S334ter line-3 rat (SD-Foxn1 Tg(S334ter)3Lav) (RD nude rat), and to test whether transplanted rat fetal retinal sheets can elicit lost responses to light.MethodsNational Institutes of Health nude rats (SD-Foxn1 Tg) with normal retina were compared to RD nude rats with and without transplant for morphology and visual function. Retinal sheets from transgenic rats expressing human placental alkaline phosphatase (hPAP) were transplanted into the subretinal space of RD nude rats between postnatal day (P) 26 and P38. Transplant morphology was examined in vivo using optical coherence tomography (OCT). Visual function was assessed by optokinetic (OKN) testing, electroretinogram (ERG), and superior colliculus (SC) electrophysiology. Cryostat sections were analyzed for various retinal/synaptic markers and for the expression of donor hPAP.ResultsOptical coherence tomography scans showed the placement and laminar development of retinal sheet transplants in the subretinal space. Optokinetic testing demonstrated a deficit in visual acuity in RD nude rats that was improved after retinal sheet transplantation. No ERG responses were detected in the RD nude rats with or without transplantation. Superior colliculus responses were absent in age-matched control and sham surgery RD nude rats; however, robust light-evoked responses were observed in a specific location in the SC of transplanted RD nude rats. Responsive regions corresponded to the area of transplant placement in the eye. The quality of visual responses correlated with transplant organization and placement.ConclusionsThe data suggest that retinal sheet transplants integrate into the host retina of RD nude rats and recover significant visual function.

Depth-dependence of visual signals in the human superior colliculus at 9.4 T.

The superior colliculus (SC) is a layered structure located in the midbrain. We exploited the improved spatial resolution and BOLD signal strength available at 9.4 T to investigate the depth profile of visual BOLD responses in the human SC based on distortion-corrected EPI data with a 1 mm isotropic resolution. We used high resolution (350 µm in-plane) anatomical images to determine regions-of-interest of the SC and applied a semi-automated method to segment it into superficial, intermediate, and deep zones. A greater than linear increase in sensitivity of the functional signal at 9.4 T allowed us to detect a statistically significant depth pattern in a group analysis with a 20 min stimulation paradigm. Descriptive data showed consistent depth profiles also in single individuals. The highest signals were localized to the superficial layers of the right and left SC during contralateral stimulation, which was in good agreement with its functional architecture known from non-human primates. This study thus demonstrates the potential of 9.4 T MRI for functional neuroimaging even in deeply located, particularly challenging brain structures such as the SC. Hum Brain Mapp 38:574-587, 2017. © 2016 Wiley Periodicals, Inc.

Express saccades and superior colliculus responses are sensitive to short-wavelength cone contrast

A key structure for directing saccadic eye movements is the superior colliculus (SC). The visual pathways that project to the SC have been reported to carry only luminance information and not color information. Short-wavelength-sensitive cones (S-cones) in the retina make little or no contribution to luminance signals, leading to the conclusion that S-cone stimuli should be invisible to SC neurons. The premise that S-cone stimuli are invisible to the SC has been used in numerous clinical and human psychophysical studies. The assumption that the SC cannot use S-cone stimuli to guide behavior has never been tested. We show here that express saccades, which depend on the SC, can be driven by S-cone input. Further, express saccade reaction times and changes in SC activity depend on the amount of S-cone contrast. These results demonstrate that the SC can use S-cone stimuli to guide behavior. We conclude that the use of S-cone stimuli is insufficient to isolate SC function in psychophysical and clinical studies of human subjects.

Superior Colliculus Responses to Attended, Unattended, and Remembered Saccade Targets during Smooth Pursuit Eye Movements.

In realistic environments, keeping track of multiple visual targets during eye movements likely involves an interaction between vision, top-down spatial attention, memory, and self-motion information. Recently we found that the superior colliculus (SC) visual memory response is attention-sensitive and continuously updated relative to gaze direction. In that study, animals were trained to remember the location of a saccade target across an intervening smooth pursuit (SP) eye movement (Dash et al., 2015). Here, we modified this paradigm to directly compare the properties of visual and memory updating responses to attended and unattended targets. Our analysis shows that during SP, active SC visual vs. memory updating responses share similar gaze-centered spatio-temporal profiles (suggesting a common mechanism), but updating was weaker by ~25%, delayed by ~55 ms, and far more dependent on attention. Further, during SP the sum of passive visual responses (to distracter stimuli) and memory updating responses (to saccade targets) closely resembled the responses for active attentional tracking of visible saccade targets. These results suggest that SP updating signals provide a damped, delayed estimate of attended location that contributes to the gaze-centered tracking of both remembered and visible saccade targets.

Midbrain auditory selectivity to natural sounds

This study investigated auditory stimulus selectivity in the midbrain superior colliculus (SC) of the echolocating bat, an animal that relies on hearing to guide its orienting behaviors. Multichannel, single-unit recordings were taken across laminae of the midbrain SC of the awake, passively listening big brown bat, Eptesicus fuscus. Species-specific frequency-modulated (FM) echolocation sound sequences with dynamic spectrotemporal features served as acoustic stimuli along with artificial sound sequences matched in bandwidth, amplitude, and duration but differing in spectrotemporal structure. Neurons in dorsal sensory regions of the bat SC responded selectively to elements within the FM sound sequences, whereas neurons in ventral sensorimotor regions showed broad response profiles to natural and artificial stimuli. Moreover, a generalized linear model (GLM) constructed on responses in the dorsal SC to artificial linear FM stimuli failed to predict responses to natural sounds and vice versa, but the GLM produced accurate response predictions in ventral SC neurons. This result suggests that auditory selectivity in the dorsal extent of the bat SC arises through nonlinear mechanisms, which extract species-specific sensory information. Importantly, auditory selectivity appeared only in responses to stimuli containing the natural statistics of acoustic signals used by the bat for spatial orientation-sonar vocalizations-offering support for the hypothesis that sensory selectivity enables rapid species-specific orienting behaviors. The results of this study are the first, to our knowledge, to show auditory spectrotemporal selectivity to natural stimuli in SC neurons and serve to inform a more general understanding of mechanisms guiding sensory selectivity for natural, goal-directed orienting behaviors.

Spatial transformations between superior colliculus visual and motor response fields during head-unrestrained gaze shifts.

We previously reported that visuomotor activity in the superior colliculus (SC)--a key midbrain structure for the generation of rapid eye movements--preferentially encodes target position relative to the eye (Te) during low-latency head-unrestrained gaze shifts (DeSouza et al., 2011). Here, we trained two monkeys to perform head-unrestrained gaze shifts after a variable post-stimulus delay (400-700 ms), to test whether temporally separated SC visual and motor responses show different spatial codes. Target positions, final gaze positions and various frames of reference (eye, head, and space) were dissociated through natural (untrained) trial-to-trial variations in behaviour. 3D eye and head orientations were recorded, and 2D response field data were fitted against multiple models by use of a statistical method reported previously (Keith et al., 2009). Of 60 neurons, 17 showed a visual response, 12 showed a motor response, and 31 showed both visual and motor responses. The combined visual response field population (n = 48) showed a significant preference for Te, which was also preferred in each visual subpopulation. In contrast, the motor response field population (n = 43) showed a preference for final (relative to initial) gaze position models, and the Te model was statistically eliminated in the motor-only population. There was also a significant shift of coding from the visual to motor response within visuomotor neurons. These data confirm that SC response fields are gaze-centred, and show a target-to-gaze transformation between visual and motor responses. Thus, visuomotor transformations can occur between, and even within, neurons within a single frame of reference and brain structure.

A Diencephalic Dopamine Source Provides Input to the Superior Colliculus, where D1 and D2 Receptors Segregate to Distinct Functional Zones.

Modulation of neural responses is frequently observed in the superior colliculus (SC), a retinorecipient midbrain structure that controls orienting and the localization of attention. Although behavioral contingencies that influence SC responses are well documented, the neural pathways and molecular mechanisms responsible for this modulation are not completely understood. Here, we illustrate a dopaminergic system that strongly impacts neural responses in the SC. After using RNA sequencing (RNA-seq) to detail the transcriptome of dopamine-related genes in the SC, we show that D1 receptors are enriched in the superficial visual SC, while D2 receptors segregate to the intermediate multimodal/motor SC. Retrograde injections into the SC consistently label A13, a small dopamine cell group located in the zona incerta. We surmise that A13 mimics dopaminergic effects that we observed in SC slices, which suggests that dopamine in the SC may reduce the tendency of an animal to orient or attend to salient stimuli.