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.

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.

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.

Columnar and Laminar Segregation of Retinal Input to the Primate Superior Colliculus Revealed by Anterograde Tracer Injection Into Each Eye.

Purpose: After the lateral geniculate nucleus, the superior colliculus is the richest target of retinal projections in primates. Hubel et al. used tritium autoradiography to show that axon terminals emanating from one eye form irregular columns in the stratum griseum superficiale. Unlabeled gaps were thought to be filled by the other eye, but this assumption was never tested directly. Methods: Experiments were performed in two normal macaques. In monkey 1, [3H]proline was injected into the left eye and the pattern of radiolabeling was examined in serial cross-sections through the entire superior colliculus. In monkey 2, cholera toxin subunit B conjugated to Alexa 488 was injected into the right eye and cholera toxin subunit B - Alexa 594 was injected into the left eye. The two fluorescent labels were compared in a reconstruction of the superior colliculus prepared from serial sections. Results: In monkey 1, irregular columns of axon terminals were present in the superficial grey. The projection from the peripheral retina was stronger than the projection from the macula. In monkey 2, the two fluorescent Alexa tracers mainly interdigitated: a conspicuous gap in one label was usually filled by a clump of the other label. There was also partial laminar segregation of ocular inputs. In the far peripheral field representation, the contralateral eye's input generally terminated closer to the tectal surface. In the midperiphery the eyes switched, bringing the ipsilateral input nearer the surface. Conclusions: Direct retinal input to the macaque superior colliculus is segregated into alternating columns and strata, despite the fact that tectal cells respond robustly to stimulation of either eye.

Organization of the inputs and outputs of the mouse superior colliculus.

The superior colliculus (SC) receives diverse and robust cortical inputs to drive a range of cognitive and sensorimotor behaviors. However, it remains unclear how descending cortical input arising from higher-order associative areas coordinate with SC sensorimotor networks to influence its outputs. Here, we construct a comprehensive map of all cortico-tectal projections and identify four collicular zones with differential cortical inputs: medial (SC.m), centromedial (SC.cm), centrolateral (SC.cl) and lateral (SC.l). Further, we delineate the distinctive brain-wide input/output organization of each collicular zone, assemble multiple parallel cortico-tecto-thalamic subnetworks, and identify the somatotopic map in the SC that displays distinguishable spatial properties from the somatotopic maps in the neocortex and basal ganglia. Finally, we characterize interactions between those cortico-tecto-thalamic and cortico-basal ganglia-thalamic subnetworks. This study provides a structural basis for understanding how SC is involved in integrating different sensory modalities, translating sensory information to motor command, and coordinating different actions in goal-directed behaviors.

Anatomy and function of retinorecipient arborization fields in zebrafish.

In 1994, Burrill and Easter described the retinal projections in embryonic and larval zebrafish, introducing the term "arborization fields" (AFs) for the retinorecipient areas. AFs were numbered from 1 to 10 according to their positions along the optic tract. With the exception of AF10 (neuropil of the optic tectum), annotations of AFs remained tentative. Here we offer an update on the likely identities and functions of zebrafish AFs after successfully matching classical neuroanatomy to the digital Max Planck Zebrafish Brain Atlas. In our system, individual AFs are neuropil areas associated with the following nuclei: AF1 with the suprachiasmatic nucleus; AF2 with the posterior parvocellular preoptic nucleus; AF3 and AF4 with the ventrolateral thalamic nucleus; AF4 with the anterior and intermediate thalamic nuclei; AF5 with the dorsal accessory optic nucleus; AF7 with the parvocellular superficial pretectal nucleus; AF8 with the central pretectal nucleus; and AF9d and AF9v with the dorsal and ventral periventricular pretectal nuclei. AF6 is probably part of the accessory optic system. Imaging, ablation, and activation experiments showed contributions of AF5 and potentially AF6 to optokinetic and optomotor reflexes, AF4 to phototaxis, and AF7 to prey detection. AF6, AF8 and AF9v respond to dimming, and AF4 and AF9d to brightening. While few annotations remain tentative, it is apparent that the larval zebrafish visual system is anatomically and functionally continuous with its adult successor and fits the general cyprinid pattern. This study illustrates the synergy created by merging classical neuroanatomy with a cellular-resolution digital brain atlas resource and functional imaging in larval zebrafish.

Corticostriatal control of defense behavior in mice induced by auditory looming cues.

Animals exhibit innate defense behaviors in response to approaching threats cued by the dynamics of sensory inputs of various modalities. The underlying neural circuits have been mostly studied in the visual system, but remain unclear for other modalities. Here, by utilizing sounds with increasing (vs. decreasing) loudness to mimic looming (vs. receding) objects, we find that looming sounds elicit stereotypical sequential defensive reactions: freezing followed by flight. Both behaviors require the activity of auditory cortex, in particular the sustained type of responses, but are differentially mediated by corticostriatal projections primarily innervating D2 neurons in the tail of the striatum and corticocollicular projections to the superior colliculus, respectively. The behavioral transition from freezing to flight can be attributed to the differential temporal dynamics of the striatal and collicular neurons in their responses to looming sound stimuli. Our results reveal an essential role of the striatum in the innate defense control.

Unraveling circuits of visual perception and cognition through the superior colliculus.

The superior colliculus is a conserved sensorimotor structure that integrates visual and other sensory information to drive reflexive behaviors. Although the evidence for this is strong and compelling, a number of experiments reveal a role for the superior colliculus in behaviors usually associated with the cerebral cortex, such as attention and decision-making. Indeed, in addition to collicular outputs targeting brainstem regions controlling movements, the superior colliculus also has ascending projections linking it to forebrain structures including the basal ganglia and amygdala, highlighting the fact that the superior colliculus, with its vast inputs and outputs, can influence processing throughout the neuraxis. Today, modern molecular and genetic methods combined with sophisticated behavioral assessments have the potential to make significant breakthroughs in our understanding of the evolution and conservation of neuronal cell types and circuits in the superior colliculus that give rise to simple and complex behaviors.

Afferent and efferent connections of the nucleus prethalamicus in the yellowfin goby Acanthogobius flavimanus.

The nucleus prethalamicus (PTh) receives fibers from the optic tectum and then projects to the dorsal telencephalon in the yellowfin goby Acanthogobius flavimanus. However, it remained unclear whether the PTh is a visual relay nucleus, because the optic tectum receives not only visual but also other sensory modalities. Furthermore, precise telencephalic regions receiving prethalamic input remained unknown in the goby. We therefore investigated the full set of afferent and efferent connections of the PTh by direct tracer injections into the nucleus. Injections into the PTh labeled cells in the optic tectum, ventromedial thalamic nucleus, central and medial parts of the dorsal telencephalon, and caudal lobe of the cerebellum. We found that the somata of most tecto-prethalamic neurons are present in the stratum periventriculare. Their dendrites ascend to reach the major retinorecipient layers of the tectum. The PTh is composed of two subnuclei (medial and lateral) and topographic organization was appreciated only for tectal projections to the lateral subnucleus (PTh-l), which also receives sparse retinal projections. In contrast, the medial subnucleus receives fibers only from the medial tectum. We found that the PTh projects to nine subregions in the dorsal telencephalon and four in the ventral telencephalon. Furthermore, cerebellar injections revealed that cerebello-prethalamic fibers cross the midline twice to innervate the PTh-l on both sides. The present study is the first detailed report on the full set of the connections of PTh, which suggests that the PTh relays visual information from the optic tectum to the telencephalon.

Depth relationships and measures of tissue thickness in dorsal midbrain.

Dorsal human midbrain contains two nuclei with clear laminar organization, the superior and inferior colliculi. These nuclei extend in depth between the superficial dorsal surface of midbrain and a deep midbrain nucleus, the periaqueductal gray matter (PAG). The PAG, in turn, surrounds the cerebral aqueduct (CA). This study examined the use of two depth metrics to characterize depth and thickness relationships within dorsal midbrain using the superficial surface of midbrain and CA as references. The first utilized nearest-neighbor Euclidean distance from one reference surface, while the second used a level-set approach that combines signed distances from both reference surfaces. Both depth methods provided similar functional depth profiles generated by saccadic eye movements in a functional MRI task, confirming their efficacy for delineating depth for superficial functional activity. Next, the boundaries of the PAG were estimated using Euclidean distance together with elliptical fitting, indicating that the PAG can be readily characterized by a smooth surface surrounding PAG. Finally, we used the level-set approach to measure tissue depth between the superficial surface and the PAG, thus characterizing the variable thickness of the colliculi. Overall, this study demonstrates depth-mapping schemes for human midbrain that enables accurate segmentation of the PAG and consistent depth and thickness estimates of the superior and inferior colliculi.

Anatomy and Connectivity of the Torus Longitudinalis of the Adult Zebrafish.

This study describes the cytoarchitecture of the torus longitudinalis (TL) in adult zebrafish by using light and electron microscopy, as well as its main connections as revealed by DiI tract tracing. In addition, by using high resolution confocal imaging followed by digital tracing, we describe the morphology of tectal pyramidal cells (type I cells) that are GFP positive in the transgenic line Tg(1.4dlx5a-dlx6a:GFP)ot1. The TL consists of numerous small and medium-sized neurons located in a longitudinal eminence attached to the medial optic tectum. A small proportion of these neurons are GABAergic. The neuropil shows three types of synaptic terminals and numerous dendrites. Tracing experiments revealed that the main efference of the TL is formed of parallel-like fibers that course within the marginal layer of the optic tectum. A toral projection to the thalamic nucleus rostrolateralis is also observed. Afferents to the TL come from visual and cerebellum-related nuclei in the pretectum, namely the central, intercalated and the paracommissural pretectal nuclei, as well as from the subvalvular nucleus in the isthmus. Additional afferents to the TL may come from the cerebellum but their origins could not be confirmed. The tectal afferent projection to the TL originates from cells similar to the type X cells described in other cyprinids. Tectal pyramidal neurons show round or piriform cell bodies, with spiny apical dendritic trees in the marginal layer. This anatomical study provides a basis for future functional and developmental studies focused on this cerebellum-like circuit in zebrafish.

Monosynaptic inputs to specific cell types of the intermediate and deep layers of the superior colliculus.

The intermediate and deep layers of the midbrain superior colliculus (SC) are a key locus for several critical functions, including spatial attention, multisensory integration, and behavioral responses. While the SC is known to integrate input from a variety of brain regions, progress in understanding how these inputs contribute to SC-dependent functions has been hindered by the paucity of data on innervation patterns to specific types of SC neurons. Here, we use G-deleted rabies virus-mediated monosynaptic tracing to identify inputs to excitatory and inhibitory neurons of the intermediate and deep SC. We observed stronger and more numerous projections to excitatory than inhibitory SC neurons. However, a subpopulation of excitatory neurons thought to mediate behavioral output received weaker inputs, from far fewer brain regions, than the overall population of excitatory neurons. Additionally, extrinsic inputs tended to target rostral excitatory and inhibitory SC neurons more strongly than their caudal counterparts, and commissural SC neurons tended to project to similar rostrocaudal positions in the other SC. Our findings support the view that active intrinsic processes are critical to SC-dependent functions, and will enable the examination of how specific inputs contribute to these functions.

The role of the optic tectum for visually evoked orienting and evasive movements.

As animals forage for food and water or evade predators, they must rapidly decide what visual features in the environment deserve attention. In vertebrates, this visuomotor computation is implemented within the neural circuits of the optic tectum (superior colliculus in mammals). However, the mechanisms by which tectum decides whether to approach or evade remain unclear, and also which neural mechanisms underlie this behavioral choice. To address this problem, we used an eye-brain-spinal cord preparation to evaluate how the lamprey responds to visual inputs with distinct stimulus-dependent motor patterns. Using ventral root activity as a behavioral readout, we classified 2 main types of fictive motor responses: (i) a unilateral burst response corresponding to orientation of the head toward slowly expanding or moving stimuli, particularly within the anterior visual field, and (ii) a unilateral or bilateral burst response triggering fictive avoidance in response to rapidly expanding looming stimuli or moving bars. A selective pharmacological blockade revealed that the brainstem-projecting neurons in the deep layer of the tectum in interaction with local inhibitory interneurons are responsible for selecting between these 2 visually triggered motor actions conveyed through downstream reticulospinal circuits. We suggest that these visual decision-making circuits had evolved in the common ancestor of vertebrates and have been conserved throughout vertebrate phylogeny.

Comparative Brain Morphology of the Greenland and Pacific Sleeper Sharks and its Functional Implications.

In cartilaginous fishes, variability in the size of the brain and its major regions is often associated with primary habitat and/or specific behavior patterns, which may allow for predictions on the relative importance of different sensory modalities. The Greenland (Somniosus microcephalus) and Pacific sleeper (S. pacificus) sharks are the only non-lamnid shark species found in the Arctic and are among the longest living vertebrates ever described. Despite a presumed visual impairment caused by the regular presence of parasitic ocular lesions, coupled with the fact that locomotory muscle power is often depressed at cold temperatures, these sharks remain capable of capturing active prey, including pinnipeds. Using magnetic resonance imaging (MRI), brain organization of S. microcephalus and S. pacificus was assessed in the context of up to 117 other cartilaginous fish species, using phylogenetic comparative techniques. Notably, the region of the brain responsible for motor control (cerebellum) is small and lacking foliation, a characteristic not yet described for any other large-bodied (>3 m) shark. Further, the development of the optic tectum is relatively reduced, while olfactory brain regions are among the largest of any shark species described to date, suggestive of an olfactory-mediated rather than a visually-mediated lifestyle.

Sensorimotor maps can be dynamically calibrated using an adaptive-filter model of the cerebellum.

Substantial experimental evidence suggests the cerebellum is involved in calibrating sensorimotor maps. Consistent with this involvement is the well-known, but little understood, massive cerebellar projection to maps in the superior colliculus. Map calibration would be a significant new role for the cerebellum given the ubiquity of map representations in the brain, but how it could perform such a task is unclear. Here we investigated a dynamic method for map calibration, based on electrophysiological recordings from the superior colliculus, that used a standard adaptive-filter cerebellar model. The method proved effective for complex distortions of both unimodal and bimodal maps, and also for predictive map-based tracking of moving targets. These results provide the first computational evidence for a novel role for the cerebellum in dynamic sensorimotor map calibration, of potential importance for coordinate alignment during ongoing motor control, and for map calibration in future biomimetic systems. This computational evidence also provides testable experimental predictions concerning the role of the connections between cerebellum and superior colliculus in previously observed dynamic coordinate transformations.

A subcortical excitatory circuit for sensory-triggered predatory hunting in mice.

Predatory hunting plays a fundamental role in animal survival. Little is known about the neural circuits that convert sensory cues into neural signals to drive this behavior. Here we identified an excitatory subcortical neural circuit from the superior colliculus to the zona incerta that triggers predatory hunting. The superior colliculus neurons that form this pathway integrate motion-related visual and vibrissal somatosensory cues of prey. During hunting, these neurons send out neural signals that are temporally correlated with predatory attacks, but not with feeding after prey capture. Synaptic inactivation of this pathway selectively blocks hunting for prey without impairing other sensory-triggered behaviors. These data reveal a subcortical neural circuit that is specifically engaged in translating sensory cues into neural signals to provoke predatory hunting.

Nucleus Isthmi Is Required to Sustain Target Pursuit during Visually Guided Prey-Catching.

Animals must frequently perform a sequence of behaviors to achieve a specific goal. However, the neural mechanisms that promote the continuation and completion of such action sequences are not well understood. Here, we characterize the anatomy, physiology, and function of the nucleus isthmi (NI), a cholinergic nucleus thought to modulate tectal-dependent, goal-directed behaviors. We find that the larval zebrafish NI establishes reciprocal connectivity with the optic tectum and identify two distinct types of isthmic projection neuron that either connect ipsilaterally to retinorecipient laminae of the tectum and pretectum or bilaterally to both tectal hemispheres. Laser ablation of NI caused highly specific deficits in tectally mediated loom-avoidance and prey-catching behavior. In the context of hunting, NI ablation did not affect prey detection or hunting initiation but resulted in larvae failing to sustain prey-tracking sequences and aborting their hunting routines. Moreover, calcium imaging revealed elevated neural activity in NI following onset of hunting behavior. We propose a model in which NI provides state-dependent feedback facilitation to the optic tectum and pretectum to potentiate neural activity and increase the probability of consecutive prey-tracking maneuvers during hunting sequences.

The sensory thalamus and visual midbrain in mouse lemurs.

Mouse lemurs are the smallest of extant primates and are thought to resemble early primates in many ways. We provide histological descriptions of the major sensory nuclei of the dorsal thalamus and the superior colliculus (SC) of mouse lemurs (Microcebus murinus). The dorsal lateral geniculate nucleus has the six layers typical of strepsirrhine primates, with matching pairs of magnocellular, parvocellular, and koniocellular layers, one of each pair for each eye. Unlike most primates, magnocellular and parvocellular layers exhibit only small differences in cell size. All layers express vesicular glutamate transporter 2 (VGLUT2), reflecting terminations of retinal inputs, and the expression of VGLUT2 is much less dense in the koniocellular layers. Parvalbumin is densely expressed in all layers, while SMI-32 is densely expressed only in the magnocellular layers. The adjoining pulvinar complex has a posterior nucleus with strong VGLUT2 expression, reflecting terminations from the SC. The SC is laminated with dense expression of VGLUT2 in the upper superficial gray layer, reflecting terminations from the retina. The ventral (MGNv), medial, and dorsal divisions of the medial geniculate complex are only moderately differentiated, although patches of dense VGLUT2 expression are found along the outer border of MGNv. The ventroposterior nucleus has darkly stained cells in Nissl stained sections, and narrow septa separating patchy regions of dense VGLUT2 expression that likely represent different body parts. Overall, these structures resemble those in other strepsirrhine primates, although they are smaller, with the sensory nuclei appearing to occupy proportionately more of the dorsal thalamus than in larger primates.

Updated functional segregation of retinal ganglion cell projections in the tectum of a cyprinid fish-further elaboration based on microelectrode recordings.

Single-unit responses of retinal ganglion cells (GCs) were recorded extracellularly from their axonal terminals in the tectum opticum (TO) of the intact fish (goldfish, carp). The depths of retinal units consecutively recorded along the track of the microelectrode were measured. At the depth of around 50 µm, the responses of six types of direction-selective (DS) GCs were regularly recorded. Responses of two types of orientation-selective (OS) GCs and detectors of white and black spots occurred approximately 50 µm deeper. Responses of GCs with dark- and light-sustained activity were recorded deeper than all others, at about 200 µm. The receptive fields of consecutively recorded units overlap, so they analyze the same fragment of the visual scene, focused by eye optic on the photoreceptor raster. The responses of pairs of DS GCs (ON and OFF units that preferred same direction of stimulus movement) and OS GCs (detectors of vertical and horizontal lines) were often simultaneously recorded at one position of the microelectrode. (The paired recordings of certain units amounted about fourth part of all recordings.) This suggests that their axonal arborizations are located close to each other in the tectal retinorecipient layer. Electrophysiological method, thus, allows to indirectly clarify and make precise the morphology of the retino-tectal connections and to establish a morpho-physiological correspondence.