Supermultipotency and unpredictability in the developing superior colliculus.

A recent study by Cheung, Pauler, Koppensteiner et al. combining lineage tracing with single-cell RNA sequencing (scRNA-seq) has revealed unexpected features of the developing superior colliculus (SC). Extremely multipotent individual progenitors generate all types of SC neurons and glial cells that were found to localize in a non-predetermined pattern, demonstrating a remarkable degree of unpredictability in SC development.

Visual shape discrimination in goldfish, modelled with the neural circuitry of optic tectum and torus longitudinalis.

There is no satisfactory neurally-based theory as to how vertebrates that lack a neocortex discriminate even simple geometric shapes. In fishes, an intact optic tectum is necessary for such discriminations, but physiological studies of it have found nothing like the hierarchically arranged feature detecting neurons of mammalian visual cortex. Here, a neural model attempts a solution by basing shape discrimination upon the responses of only those elementary detectors (e.g. of size) that are within a focus of attention, formed by a winner-take-all arrangement of retinotopically mapped units representing tectal pyramidal cells. While this relatively primitive mechanism could recognize an object irrespective of position in space, it fails to distinguish patterns that differ only in their features' spatial relationships. The model's solution - imitating goldfish that naturally attend to the top of shapes - is to shift attention to the edges of a shape by spatially offsetting inputs to the pyramidal neurons, effected by the torus longitudinalis and its prolific synapses on pyramidal dendrites. The model's shape discrimination was compared to an extensive behavioral study using shapes with points and projections. In one test series fish were sensitive to the relative number of points on the tops of shapes. In another, fish were trained to discriminate points on the sides. By using different offset connections and only one elementary feature detector for small dark spots, the model successfully emulated the two sets of goldfish data, as judged by significant correlations between model response and fish discrimination.

Predation without direction selectivity.

Across the animal kingdom, visual predation relies on motion-sensing neurons in the superior colliculus (SC) and its orthologs. These neurons exhibit complex stimulus preferences, including direction selectivity, which is thought to be critical for tracking the unpredictable escape routes of prey. The source of direction selectivity in the SC is contested, and its contributions to predation have not been tested experimentally. Here, we use type-specific cell removal to show that narrow-field (NF) neurons in the mouse SC guide predation. In vivo recordings demonstrate that direction-selective responses of NF cells are independent of recently reported stimulus-edge effects. Monosynaptic retrograde tracing reveals that NF cells receive synaptic input from direction-selective ganglion cells. When we eliminate direction selectivity in the retina of adult mice, direction-selective responses in the SC, including in NF cells, are lost. However, eliminating retinal direction selectivity does not affect the hunting success or strategies of mice, even when direction selectivity is removed after mice have learned to hunt, and despite abolishing the gaze-stabilizing optokinetic reflex. Thus, our results identify the retinal source of direction selectivity in the SC. They show that NF cells in the SC guide predation, an essential spatial orienting task, independent of their direction selectivity, revealing behavioral multiplexing of complex neural feature preferences and highlighting the importance of feature-selective manipulations for neuroethology.

Prefrontal control of superior colliculus modulates innate escape behavior following adversity.

Innate defensive responses, though primarily instinctive, must also be highly adaptive to changes in risk assessment. However, adaptive changes can become maladaptive, following severe stress, as seen in posttraumatic stress disorder (PTSD). In a series of experiments, we observed long-term changes in innate escape behavior of male mice towards a previously non-threatening stimulus following an adverse shock experience manifested as a shift in the threshold of threat response. By recording neural activity in the superior colliculus (SC) while phototagging specific responses to afferents, we established the crucial influence of input arriving at the SC from the medial prefrontal cortex (mPFC), both directly and indirectly, on escape-related activity after adverse shock experience. Inactivating these specific projections during the shock effectively abolished the observed changes. Conversely, optogenetically activating them during encounters controlled escape responses. This establishes the necessity and sufficiency of those specific mPFC inputs into the SC for adverse experience related changes in innate escape behavior.

Distribution, development, and identity of retinal ganglion cells labeled in the Sert-Cre reporter mouse.

The mouse retina contains over 40 types of retinal ganglion cells (RGCs) that differ in morphology, function, or gene expression. RGCs also differ by whether their axons target the brain.s ipsilateral or contralateral hemisphere. Contralaterally projecting RGCs (contraRGCs) are widespread in mouse retina, whereas ipsilateral projecting RGCs (ipsiRGCs) are confined to the ventro-temporal (VT) crescent of retina. In this study, we employed the Sert-Cre transgenic line, which had been reported to selectively label ipsiRGCs, to study ipsiRGCs during development. Although the number of Cre-expressing ipsiRGCs did not significantly increase with postnatal age, the region of retina that they occupied did, and by adulthood represented ~30% of the retinal surface. Unexpectedly, genetic ablation of Sert-Cre cells failed to fully disrupt ipsilateral projecting retinal axons, suggesting that not all ipsiRGCs generated Cre in Sert-Cre mice. To test this hypothesis, we retrogradely labeled ipsiRGCs in Sert-Cre mice which revealed that not all ipsiRGCs are labeled in Sert-Cre mice and a small population of contraRGCs flanking the VT crescent generates Cre in this line. These results do not negate the usefulness of the Sert-Cre mouse but do raise important caveats to the interpretation of such studies.

Retinal origin of orientation but not direction selective maps in the superior colliculus.

Neurons in the mouse superior colliculus ("colliculus") are arranged in ordered spatial maps. While orientation-selective (OS) neurons form a concentric map aligned to the center of vision, direction-selective (DS) neurons are arranged in patches with changing preferences across the visual field. It remains unclear whether these maps are a consequence of feedforward input from the retina or local computations in the colliculus. To determine whether these maps originate in the retina, we mapped the local and global distribution of OS and DS retinal ganglion cell axon boutons using in vivo two-photon calcium imaging. We found that OS boutons formed patches that matched the distribution of OS neurons within the colliculus. DS boutons displayed fewer regional specializations, better reflecting the organization of DS neurons in the retina. Both eyes convey similar orientation but different DS inputs to the colliculus, as shown in recordings from retinal explants. These data demonstrate that orientation and direction maps within the colliculus are independent, where orientation maps are likely inherited from the retina, but direction maps require additional computations.

Rat superior colliculus encodes the transition between static and dynamic vision modes.

The visual continuity illusion involves a shift in visual perception from static to dynamic vision modes when the stimuli arrive at high temporal frequency, and is critical for recognizing objects moving in the environment. However, how this illusion is encoded across the visual pathway remains poorly understood, with disparate frequency thresholds at retinal, cortical, and behavioural levels suggesting the involvement of other brain areas. Here, we employ a multimodal approach encompassing behaviour, whole-brain functional MRI, and electrophysiological measurements, for investigating the encoding of the continuity illusion in rats. Behavioural experiments report a frequency threshold of 18±2 Hz. Functional MRI reveal that superior colliculus signals transition from positive to negative at the behaviourally-driven threshold, unlike thalamic and cortical areas. Electrophysiological recordings indicate that these transitions are underpinned by neural activation/suppression. Lesions in the primary visual cortex reveal this effect to be intrinsic to the superior colliculus (under a cortical gain effect). Our findings highlight the superior colliculus' crucial involvement in encoding temporal frequency shifts, especially the change from static to dynamic vision modes.

Measuring spatial visual loss in rats by retinotopic mapping of the superior colliculus using a novel multi-electrode array technique.

BACKGROUND: The retinotopic map property of the superior colliculus (SC) is a reliable indicator of visual functional changes in rodents. Electrophysiological mapping of the SC using a single electrode has been employed for measuring visual function in rat and mouse disease models. Single electrode mapping is highly laborious requiring long-term exposure to the SC surface and prolonged anesthetic conditions that can adversely affect the mapping data. NEW METHOD: To avoid the above-mentioned issues, we fabricated a fifty-six (56) electrode multi-electrode array (MEA) for rapid and reliable visual functional mapping of the SC. Since SC is a dome-shaped structure, the array was made of electrodes with dissimilar tip lengths to enable simultaneous and uniform penetration of the SC. RESULTS: SC mapping using the new MEA was conducted in retinal degenerate (RD) Royal College of Surgeons (RCS) rats and rats with focal retinal damage induced by green diode laser. For SC mapping, the MEA was advanced into the SC surface and the visual activities were recorded during full-filed light stimulation of the eye. Based on the morphological examination, the MEA electrodes covered most of the exposed SC area and penetrated the SC surface at a relatively uniform depth. MEA mapping in RCS rats (n=9) demonstrated progressive development of a scotoma in the SC that corresponded to the degree of photoreceptor loss. MEA mapping in the laser damaged rats demonstrated the presence of a scotoma in the SC area that corresponded to the location of retinal laser injury. COMPARISON WITH EXISTING METHODS AND CONCLUSIONS: The use of MEA for SC mapping is advantageous over single electrode recording by enabling faster recordings and reducing anesthesia time. This study establishes the feasibility of the MEA technique for rapid and efficient SC mapping, particularly advantageous for evaluating therapeutic effects in retinal degenerate rat disease models.

Involvement of superior colliculus in complex figure detection of mice.

Object detection is an essential function of the visual system. Although the visual cortex plays an important role in object detection, the superior colliculus can support detection when the visual cortex is ablated or silenced. Moreover, it has been shown that superficial layers of mouse SC (sSC) encode visual features of complex objects, and that this code is not inherited from the primary visual cortex. This suggests that mouse sSC may provide a significant contribution to complex object vision. Here, we use optogenetics to show that mouse sSC is involved in figure detection based on differences in figure contrast, orientation, and phase. Additionally, our neural recordings show that in mouse sSC, image elements that belong to a figure elicit stronger activity than those same elements when they are part of the background. The discriminability of this neural code is higher for correct trials than for incorrect trials. Our results provide new insight into the behavioral relevance of the visual processing that takes place in sSC.

Bilateral Retinofugal Pathfinding Impairments Limit Behavioral Compensation in Near-Congenital One-Eyed Xenopus laevis.

To generate a coherent visual percept, information from both eyes must be appropriately transmitted into the brain, where binocular integration forms the substrate for visuomotor behaviors. To establish the anatomical substrate for binocular integration, the presence of bilateral eyes and interaction of both optic nerves during retinotectal development play a key role. However, the extent to which embryonic monocularly derived visual circuits can convey visuomotor behaviors is unknown. In this study, we assessed the retinotectal anatomy and visuomotor performance of embryonically generated one-eyed tadpoles. In one-eyed animals, the axons of retinal ganglion cells from the singular remaining eye exhibited striking irregularities in their central projections in the brain, generating a noncanonical ipsilateral retinotectal projection. This data is indicative of impaired pathfinding abilities. We further show that these novel projections are correlated with an impairment of behavioral compensation for the loss of one eye.

Specific rules for time and space of multisensory plasticity in the superior colliculus.

Cat superior colliculus (SC) neurons commonly combine information from different senses, which facilitates event detection and localization. Integration in SC multisensory neurons depends on the spatial and temporal relationships between cross-modal cues. Here, we revealed the parallel process of short-term plasticity in the temporal/spatial integration process during adulthood that adapts multisensory integration to reliable changes in environmental conditions. Short-term experience alters the temporal preferences of SC multisensory neurons, and this short-term plasticity in the temporal/spatial integration process is limited to changes in cross-modal timing (a factor commonly induced by events at different distances from the receiver). However, this plasticity was not evident in response to changes in the cross-modal spatial configuration.

Neural connections of the torus semicircularis in the adult Zebrafish.

The torus semicircularis (TS) of teleosts is a key midbrain center of the lateral line and acoustic sensory systems. To characterize the TS in adult zebrafish, we studied their connections using the carbocyanine tracers applied to the TS and to other related nuclei and tracts. Two main TS nuclei, central and ventrolateral, were differentiable by their afferent connections. From central TS, (TSc) numerous toropetal cells were labeled bilaterally in several primary octaval nuclei (anterior, magnocellular, descending, and posterior octaval nuclei), in the secondary octaval nucleus, in the caudal octavolateralis nucleus, and in the perilemniscular region. In the midbrain, numerous toropetal cells were labeled in the contralateral TSc. In the diencephalon, toropetal cells labeled from the TSc were observed ipsilaterally in the medial prethalamic nucleus and the periventricular posterior tubercle nucleus. TSc toropetal neurons were also labeled bilaterally in the hypothalamic anterior tuberal nucleus (ATN) and ipsilaterally in the parvicellular preoptic nucleus but not in the telencephalon. Tracer application to the medial octavolateralis nucleus revealed contralateral projections to the ventrolateral TS (TSvl), whereas tracer application to the secondary octaval nucleus labeled fibers bilaterally in TSc and neurons in rostral TSc. The TSc sends ascending fibers to the ipsilateral lateral preglomerular region that, in turn, projects to the pallium. Application of DiI to the optic tectum labeled cells and fibers in the TSvl, whereas application of DiI to the ATN labeled cells and fibers in the TSc. These results reveal that the TSvl and TSc are mainly related with the mechanosensory lateral line and acoustic centers, respectively, and that they show different higher order connections.

Inhibitory tagging both speeds and strengthens saccade target selection in the superior colliculus during visual search.

It has been suggested that, during difficult visual search tasks involving time pressure and multiple saccades, inhibitory tagging helps to facilitate efficient saccade target selection by reducing responses to objects in the scene once they have been searched and rejected. The superior colliculus (SC) is a midbrain structure involved in target selection, and recent findings suggest an influence of inhibitory tagging on SC activity. Precisely how, and by how much, inhibitory tagging influences target selection by SC neurons, however, is unclear. The purpose of this study, therefore, was to characterize and quantify the influence of inhibitory tagging on target selection in the SC. Rhesus monkeys performed a visual search task involving time pressure and multiple saccades. Early in the fixation period between saccades in the context of this task, a subset of SC neurons reliably discriminated the stimulus selected as the next saccade goal, consistent with a role in target selection. Discrimination occurred earlier and was more robust, however, when unselected stimuli in the search array had been previously fixated on the same trial. This indicates that inhibitory tagging both speeds and strengthens saccade target selection in the SC during multisaccade search. The results provide constraints on models of target selection based on SC activity.NEW & NOTEWORTHY An important aspect of efficient behavior during difficult, time-limited visual search tasks is the efficient selection of sequential saccade targets. Inhibitory tagging, i.e., a reduction of neural activity associated with previously fixated objects, may help to facilitate such efficient selection by modulating the selection process in the superior colliculus (SC). In this study, we characterized and quantified this modulation and found that, indeed, inhibitory tagging both speeds and strengthens target selection in the SC.

A developmental critical period for ocular dominance plasticity of binocular neurons in mouse superior colliculus.

Detecting visual features in the environment is crucial for animals' survival. The superior colliculus (SC) is implicated in motion detection and processing, whereas how the SC integrates visual inputs from the two eyes remains unclear. Using in vivo electrophysiology, we show that mouse SC contains many binocular neurons that display robust ocular dominance (OD) plasticity in a critical period during early development, which is similar to, but not dependent on, the primary visual cortex. NR2A- and NR2B-containing N-methyl-D-aspartate (NMDA) receptors play an essential role in the regulation of SC plasticity. Blocking NMDA receptors can largely prevent the impairment of predatory hunting caused by monocular deprivation, indicating that maintaining the binocularity of SC neurons is required for efficient hunting behavior. Together, our studies reveal the existence and function of OD plasticity in SC, which broadens our understanding of the development of subcortical visual circuitry relating to motion detection and predatory hunting.

The superior colliculus motor region does not respond to finger tapping movements in humans.

Electrophysiological studies in macaques and functional neuroimaging in humans revealed a motor region in the superior colliculus (SC) for upper limb reaching movements. Connectivity studies in macaques reported direct connections between this SC motor region and cortical premotor arm, hand, and finger regions. These findings motivated us to investigate if the human SC is also involved in sequential finger tapping movements. We analyzed fMRI task data of 130 subjects executing finger tapping from the Human Connectome Project. While we found strong signals in the SC for visual cues, we found no signals related to simple finger tapping. In subsequent experimental measurements, we searched for responses in the SC corresponding to complex above simple finger tapping sequences. We observed expected signal increases in cortical motor and premotor regions for complex compared to simple finger tapping, but no signal increases in the motor region of the SC. Despite evidence for direct anatomical connections of the SC motor region and cortical premotor hand and finger areas in macaques, our results suggest that the SC is not involved in simple or complex finger tapping in humans.

BRCA1 and ELK-1 regulate neural progenitor cell fate in the optic tectum in response to visual experience in Xenopus laevis tadpoles.

In developing Xenopus tadpoles, the optic tectum begins to receive patterned visual input while visuomotor circuits are still undergoing neurogenesis and circuit assembly. This visual input regulates neural progenitor cell fate decisions such that maintaining tadpoles in the dark increases proliferation, expanding the progenitor pool, while visual stimulation promotes neuronal differentiation. To identify regulators of activity-dependent neural progenitor cell fate, we profiled the transcriptomes of proliferating neural progenitor cells and newly differentiated neurons using RNA-Seq. We used advanced bioinformatic analysis of 1,130 differentially expressed transcripts to identify six differentially regulated transcriptional regulators, including Breast Cancer 1 (BRCA1) and the ETS-family transcription factor, ELK-1, which are predicted to regulate the majority of the other differentially expressed transcripts. BRCA1 is known for its role in cancers, but relatively little is known about its potential role in regulating neural progenitor cell fate. ELK-1 is a multifunctional transcription factor which regulates immediate early gene expression. We investigated the potential functions of BRCA1 and ELK-1 in activity-regulated neurogenesis in the tadpole visual system using in vivo time-lapse imaging to monitor the fate of GFP-expressing SOX2+ neural progenitor cells in the optic tectum. Our longitudinal in vivo imaging analysis showed that knockdown of either BRCA1 or ELK-1 altered the fates of neural progenitor cells and furthermore that the effects of visual experience on neurogenesis depend on BRCA1 and ELK-1 expression. These studies provide insight into the potential mechanisms by which neural activity affects neural progenitor cell fate.

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.

The postnatal development of retinal projections in strepsirrhine galagos (Otolemur garnettii).

Here, we describe the postnatal development of retinal projections in galagos. Galagos are of special interest as they represent the understudied strepsirrhine branch (galagos, pottos, lorises, and lemurs) of the primate radiations. The projections of both eyes were revealed in each galago by injecting red or green cholera toxin subunit B (CTB) tracers into different eyes of galagos ranging from postnatal day 5 to adult. In the dorsal lateral geniculate nucleus, the magnocellular, parvocellular, and koniocellular layers were clearly labeled and identified by having inputs from the ipsilateral or contralateral eye at all ages. In the superficial layers of the superior colliculus, the terminations from the ipsilateral eye were just ventral to those from the contralateral eye at all ages. Other terminations at postnatal day 5 and later were in the pregeniculate nucleus, the accessory optic system, and the pretectum. As in other primates, a small retinal projection terminated in the posterior part of the pulvinar, which is known to project to the temporal visual cortex. This small projection from both eyes was most apparent on day 5 and absent in mature galagos. A similar reduction over postnatal maturation has been reported in marmosets, leading to the speculation that early retinal inputs to the pulvinar are responsible for the activation and early maturation of the middle temporal visual area, MT.

Brainstem Neural Circuits Triggering Vertical Saccades and Fixation.

Neurons in the nucleus raphe interpositus have tonic activity that suppresses saccadic burst neurons (BNs) during eye fixations, and that is inhibited before and during saccades in all directions (omnipause neurons, OPNs). We have previously demonstrated via intracellular recording and anatomical staining in anesthetized cats of both sexes that OPNs are inhibited by BNs in the medullary reticular formation (horizontal inhibitory BNs, IBNs). These horizontal IBNs receive monosynaptic input from the caudal horizontal saccade area of the superior colliculus (SC), and then produce monosynaptic inhibition in OPNs, providing a mechanism to trigger saccades. However, it is well known that the neural circuits driving horizontal components of saccades are independent from the circuits driving vertical components. Thus, our previous results are unable to explain how purely vertical saccades are triggered. Here, we again apply intracellular recording to show that a disynaptic vertical IBN circuit exists, analogous to the horizontal circuit. Specifically, we show that stimulation of the SC rostral vertical saccade area produces disynaptic inhibition in OPNs, which is not abolished by midline section between the horizontal IBNs. This excludes the possibility that horizontal IBNs could be responsible for the OPN inhibition during vertical saccades. We then show that vertical IBNs in the interstitial nucleus of Cajal, which receive monosynaptic input from rostral SC, are responsible for the disynaptic inhibition of OPNs. These results indicate that a similarly functioning SC-IBN-OPN circuit exists for both the horizontal and vertical oculomotor pathways. These two IBN-mediated circuits are capable of triggering saccades in any direction.Significance Statement Saccades shift gaze to objects of interest, moving their image to the central retina, where it is maintained for detailed examination (fixation). During fixation, high gain saccade burst neurons (BNs) are tonically inhibited by omnipause neurons (OPNs). Our previous study showed that medullary horizontal inhibitory BNs (IBNs) activated from the caudal superior colliculus (SC) inhibit tonically active OPNs in order to initiate horizontal saccades. The present study addresses the source of OPN inhibition for vertical saccades. We find that OPNs monosynaptically inhibit vertical IBNs in the interstitial nucleus of Cajal during fixation. Those same vertical IBNs are activated by the rostral SC, and inhibit OPN activity to initiate vertical saccades.

Age-related anatomical variation and morphometric studies on the optic tectum in post-hatch broiler chicken.

In this investigation the morphological and morphometrical features of the optic tectum in post-hatch broiler chicken were studied macroscopically and microscopically. The present study was conducted on 70 day old broiler chicks which were reared up to 42 days. The whole experimental period of study was divided into seven groups (from group I to VII) at weekly interval (days 0, 7, 14, 21, 28, 35 and 42). The optic lobes were paired and spherical to oval eminences located on the ventro-lateral part of the midbrain in broiler chicken. There was significant increase in length and width of the optic lobes with the advancement of age. Histological analysis of optic tectum shows six basic layers from the external surface to internal one towards the optic ventricle. Different layers of optic tectum were identified as stratum opticum, stratum griseum superficial, stratum griseum central, stratum album central, stratum griseum periventriculare and stratum fibrosum periventriculare with several types of neurons. Among all six layers of the optic tectum the stratum griseum superficial layer showed very high degree of secondry differentiation and evolved into nine sub- layers in all age groups of broiler chickens. Three main cell types had been identified that is, small to medium sized stellate shaped neuron, pyramidal neuron and fusiform neuron, beside these multipolar neuron were also evident. The thickness of all layers of optic tectum significantly increases with the advancement of age of the birds. The optic ventricle was lined with a layer of cuboidal ependymal cells.