Protocadherin 19 regulates axon guidance in the developing Xenopus retinotectal pathway.

Protocadherin 19 (Pcdh19) is a homophilic cell adhesion molecule and is involved in a variety of neuronal functions. Here, we tested whether Pcdh19 has a regulatory role in axon guidance using the developing Xenopus retinotectal system. We performed targeted microinjections of a translation blocking antisense morpholino oligonucleotide to knock down the expression of Pcdh19 selectively in the central nervous system. Knocking down Pcdh19 expression resulted in navigational errors of retinal ganglion cell (RGC) axons specifically at the optic chiasm. Instead of projecting to the contralateral optic tectum, RGC axons in the Pcdh19-depleted embryo misprojected ipsilaterally. Although incorrectly delivered into the ipsilateral brain hemisphere, these axons correctly reached the optic tectum. These data suggest that Pcdh19 has a critical role in preventing mixing of RGC axons originating from the opposite eyes at the optic chiasm, highlighting the importance of cell adhesion in bundling of RGC axons.

Neuronal Stability, Volumetric Changes, and Decrease in GFAP Expression of Marmoset (Callithrix jacchus) Subcortical Visual Nuclei During Aging.

The physiological aging process is well known for functional decline in visual abilities. Among the components of the visual system, the dorsal lateral geniculate nucleus (DLG) and superior colliculus (SC) provide a good model for aging investigations, as these structures constitute the main visual pathways for retinal inputs reaching the visual cortex. However, there are limited data available on quantitative morphological and neurochemical aspects in DLG and SC across lifespan. Here, we used optical density to determine immunoexpression of glial fibrillary acidic protein (GFAP) and design-based stereological probes to estimate the neuronal number, total volume, and layer volume of the DLG and SC in marmosets (Callithrix jacchus), ranging from 36 to 143 months of age. Our results revealed an age-related increase in total volume and layer volume of the DLG, with an overall stability in SC volume. Furthermore, a stable neuronal number was demonstrated in DLG and superficial layers of SC (SCv). A decrease in GFAP immunoexpression was observed in both visual centers. The results indicate region-specific variability in volumetric parameter, possibly attributed to structural plastic events in response to inflammation and compensatory mechanisms at the cellular and subcellular level. Additionally, the DLG and SCv seem to be less vulnerable to aging effects in terms of neuronal number. The neuropeptidergic data suggest that reduced GFAP expression may reflect morphological atrophy in the astroglial cells. This study contributes to updating the current understanding of aging effects in the visual system and stablishes a crucial foundation for future research on visual perception throughout the aging process.

Excitatory Projections of Wide Field Collicular Neurons to the Nucleus of the Optic Tract in the Rat.

The superficial layers of the mammalian superior colliculus (SC) contain neurons that are generally responsive to visual stimuli but can differ considerably in morphology and response properties. To elucidate the structure and function of these neurons, we combined extracellular recording and juxtacellular labeling, detailed anatomical reconstruction, and ultrastructural analysis of the synaptic contacts of labeled neurons, using transmission electron microscopy. Our labeled neurons project to different brainstem nuclei. Of particular importance are neurons that fit the morphological criteria of the wide field (WF) neurons and whose dendrites are horizontally oriented. They display a rather characteristic axonal projection pattern to the nucleus of optic tract (NOT); thus, we call them superior collicular WF projecting to the NOT (SCWFNOT) neurons. We corroborated the morphological characterization of this neuronal type as a distinct neuronal class with the help of unsupervised hierarchical cluster analysis. Our ultrastructural data demonstrate that SCWFNOT neurons establish excitatory connections with their targets in the NOT. Although, in rodents, the literature about the WF neurons has focused on their extensive projection to the lateral posterior nucleus of the thalamus, as a conduit for information to reach the visual association areas of the cortex, our data suggest that this subclass of WF neurons may participate in the optokinetic nystagmus.

Kinetic features dictate sensorimotor alignment in the superior colliculus.

The execution of goal-oriented behaviours requires a spatially coherent alignment between sensory and motor maps. The current model for sensorimotor transformation in the superior colliculus relies on the topographic mapping of static spatial receptive fields onto movement endpoints1-6. Here, to experimentally assess the validity of this canonical static model of alignment, we dissected the visuo-motor network in the superior colliculus and performed in vivo intracellular and extracellular recordings across layers, in restrained and unrestrained conditions, to assess both the motor and the visual tuning of individual motor and premotor neurons. We found that collicular motor units have poorly defined visual static spatial receptive fields and respond instead to kinetic visual features, revealing the existence of a direct alignment in vectorial space between sensory and movement vectors, rather than between spatial receptive fields and movement endpoints as canonically hypothesized. We show that a neural network built according to these kinetic alignment principles is ideally placed to sustain ethological behaviours such as the rapid interception of moving and static targets. These findings reveal a novel dimension of the sensorimotor alignment process. By extending the alignment from the static to the kinetic domain this work provides a novel conceptual framework for understanding the nature of sensorimotor convergence and its relevance in guiding goal-directed behaviours.

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 40 ms 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.

Cross-modal enhancement of defensive behavior via parabigemino-collicular projections.

Effective detection and avoidance from environmental threats are crucial for animals' survival. Integration of sensory cues associated with threats across different modalities can significantly enhance animals' detection and behavioral responses. However, the neural circuit-level mechanisms underlying the modulation of defensive behavior or fear response under simultaneous multimodal sensory inputs remain poorly understood. Here, we report in mice that bimodal looming stimuli combining coherent visual and auditory signals elicit more robust defensive/fear reactions than unimodal stimuli. These include intensified escape and prolonged hiding, suggesting a heightened defensive/fear state. These various responses depend on the activity of the superior colliculus (SC), while its downstream nucleus, the parabigeminal nucleus (PBG), predominantly influences the duration of hiding behavior. PBG temporally integrates visual and auditory signals and enhances the salience of threat signals by amplifying SC sensory responses through its feedback projection to the visual layer of the SC. Our results suggest an evolutionarily conserved pathway in defense circuits for multisensory integration and cross-modality enhancement.

Transcriptomic changes in the posterior pallium of male zebra finches associated with social niche conformance.

Animals plastically adjust their physiological and behavioural phenotypes to conform to their social environment-social niche conformance. The degree of sexual competition is a critical part of the social environment to which animals adjust their phenotypes, but the underlying genetic mechanisms are poorly understood. We conducted a study to investigate how differences in sperm competition risk affect the gene expression profiles of the testes and two brain areas (posterior pallium and optic tectum) in breeding male zebra finches (Taeniopygia castanotis). In this pre-registered study, we investigated a large sample of 59 individual transcriptomes. We compared two experimental groups: males held in single breeding pairs (low sexual competition) versus those held in two pairs (elevated sexual competition) per breeding cage. Using weighted gene co-expression network analysis (WGCNA), we observed significant effects of the social treatment in all three tissues. However, only the treatment effects found in the pallium were confirmed by an additional randomisation test for statistical robustness. Likewise, the differential gene expression analysis revealed treatment effects only in the posterior pallium (ten genes) and optic tectum (six genes). No treatment effects were found in the testis at the single gene level. Thus, our experiments do not provide strong evidence for transcriptomic adjustment specific to manipulated sperm competition risk. However, we did observe transcriptomic adjustments to the manipulated social environment in the posterior pallium. These effects were polygenic rather than based on few individual genes with strong effects. Our findings are discussed in relation to an accompanying paper using the same animals, which reports behavioural results consistent with the results presented here.

Early Development of the Thalamo-Pallial Stage of the Tectofugal Visual Pathway in the Chicken (Gallus gallus).

The tectofugal pathway is a highly conserved visual pathway in all amniotes. In birds and mammals, retinorecipient neurons located in the midbrain roof (optic tectum/superior colliculus) are the source of ascending projections to thalamic relays (nucleus rotundus/caudal pulvinar), which in turn project to specific pallial regions (visual dorsal ventricular ridge [vDVR]/temporal cortex) organized according to a columnar recurrent arrangement of interlaminar circuits. Whether or to which extent these striking hodological correspondences arise from comparable developmental processes is at present an open question, mainly due to the scarcity of data about the ontogeny of the avian tectofugal system. Most of the previous developmental studies of this system in birds have focused on the establishment of the retino-tecto-thalamic connectivity, overlooking the development of the thalamo-pallial-intrapallial circuit. In this work, we studied the latter in chicken embryos by means of immunohistochemical assays and precise ex vivo crystalline injections of biocytin and DiI. We found that the layered organization of the vDVR as well as the system of homotopic reciprocal connections between vDVR layers were present as early as E8. A highly organized thalamo-vDVR projection was also present at this stage. Our immunohistochemical assays suggest that both systems of projections emerge simultaneously even earlier. Combined with previous findings, these results reveal that, in striking contrast with mammals, the peripheral and central stages of the avian tectofugal pathway develop along different timelines, with a tecto-thalamo-intrapallial organization arising before and possibly independently of the retino-isthmo-tectal circuit.

Astroglial networks control visual responses of superior collicular neurons and sensory-motor behavior.

Astroglial networks closely interact with neuronal populations, but their functional contribution to neuronal representation of sensory information remains unexplored. The superior colliculus (SC) integrates multi-sensory information by generating distinct spatial patterns of neuronal functional responses to specific sensory stimulation. Here, we report that astrocytes from the mouse SC form extensive networks in the retinorecipient layer compared to visual cortex. This strong astroglial connectivity relies on high expression of gap-junction proteins. Genetic disruption of this connectivity functionally impairs SC retinotopic and orientation preference responses. These alterations are region specific, absent in primary visual cortex, and associated at the circuit level with a specific impairment of collicular neurons synaptic transmission. This has implications for SC-related visually induced innate behavior, as disrupting astroglial networks impairs light-evoked temporary arrest. Our results indicate that astroglial networks shape synaptic circuit activity underlying SC functional visual responses and play a crucial role in integrating visual cues to drive sensory-motor behavior.

Live Imaging and Characterization of Microglia Dynamics in the Zebrafish Embryo.

Microglia are highly dynamic cells and their migration and colonization of the brain parenchyma is a crucial step for proper brain development and function. Externally developing zebrafish embryos possess optical transparency, which along with well-characterized transgenic reporter lines that fluorescently label microglia, make zebrafish an ideal vertebrate model for such studies. In this paper, we take advantage of the unique features of the zebrafish model to visualize the dynamics of microglia cells in vivo and under physiological conditions. We use confocal microscopy to record a timelapse of microglia cells in the optic tectum of the zebrafish embryo and then, extract tracking data using the IMARIS 10.0 software to obtain the cells' migration path, mean speed, and distribution in the optic tectum at different developmental stages. This protocol can be a useful tool to elucidate the physiological significance of microglia behavior in various contexts, contributing to a deeper characterization of these highly motile cells.

Alternating bilateral sensory stimulation alleviates alcohol-induced conditioned place preference via a superior colliculus-VTA circuit.

Alcohol is the most widely used addictive substance, potentially leading to brain damage and genetic abnormalities. Despite its prevalence and associated risks, current treatments have yet to identify effective methods for reducing cravings and preventing relapse. In this study, we find that 4-Hz alternating bilateral sensory stimulation (ABS) effectively reduces ethanol-induced conditioned place preference (CPP) in male mice, while 4-Hz flash light does not exhibit therapeutic effects. Whole-brain c-Fos mapping demonstrates that 4-Hz ABS triggers notable activation in superior colliculus GABAergic neurons (SCGABA). SCGABA forms monosynaptic connections with ventral tegmental area dopaminergic neurons (VTADA), which is implicated in ethanol-induced CPP. Bidirectional chemogenetic manipulation of SC-VTA circuit either replicates or blocks the therapeutic effects of 4-Hz ABS on ethanol-induced CPP. These findings elucidate the role of SC-VTA circuit for alleviating ethanol-related CPP by 4-Hz ABS and point to a non-drug and non-invasive approach that might have potential for treating alcohol use disorder.

A non-image-forming visual circuit mediates the innate fear of heights in male mice.

The neural basis of fear of heights remains largely unknown. In this study, we investigated the fear response to heights in male mice and observed characteristic aversive behaviors resembling human height vertigo. We identified visual input as a critical factor in mouse reactions to heights, while peripheral vestibular input was found to be nonessential for fear of heights. Unexpectedly, we found that fear of heights in naïve mice does not rely on image-forming visual processing by the primary visual cortex. Instead, a subset of neurons in the ventral lateral geniculate nucleus (vLGN), which connects to the lateral/ventrolateral periaqueductal gray (l/vlPAG), drives the expression of fear associated with heights. Additionally, we observed that a subcortical visual pathway linking the superior colliculus to the lateral posterior thalamic nucleus inhibits the defensive response to height threats. These findings highlight a rapid fear response to height threats through a subcortical visual and defensive pathway from the vLGN to the l/vlPAG.

Transcriptional control of visual neural circuit development by GS homeobox 1.

As essential components of gene expression networks, transcription factors regulate neural circuit assembly. The homeobox transcription factor encoding gene, gs homeobox 1 (gsx1), is expressed in the developing visual system; however, no studies have examined its role in visual system formation. In zebrafish, retinal ganglion cell (RGC) axons that transmit visual information to the brain terminate in ten arborization fields (AFs) in the optic tectum (TeO), pretectum (Pr), and thalamus. Pretectal AFs (AF1-AF9) mediate distinct visual behaviors, yet we understand less about their development compared to AF10 in the TeO. Using gsx1 zebrafish mutants, immunohistochemistry, and transgenic lines, we observed that gsx1 is required for vesicular glutamate transporter, Tg(slc17a6b:DsRed), expression in the Pr, but not overall neuron number. gsx1 mutants have normal eye morphology, yet they exhibit impaired visual ability during prey capture. RGC axon volume in the gsx1 mutant Pr and TeO is reduced, and AF7 that is active during feeding is missing which is consistent with reduced hunting performance. Timed laser ablation of Tg(slc17a6b:DsRed)-positive cells reveals that they are necessary for AF7 formation. This work is the first to implicate gsx1 in establishing cell identity and functional neural circuits in the visual system.

Processing of fearful faces exhibits characteristics of subcortical functions.

A subcortical pathway is thought to have evolved to facilitate fear information transmission, but direct evidence for its existence in humans is lacking. In recent years, rapid, preattentive, and preconscious fear processing has been demonstrated, providing indirect support for the existence of the subcortical pathway by challenging the necessity of canonical cortical pathways in fear processing. However, direct support also requires evidence for the involvement of subcortical regions in fear processing. To address this issue, here we investigate whether fear processing reflects the characteristics of the subcortical structures in the hypothesized subcortical pathway. Using a monocular/dichoptic paradigm, Experiment 1 demonstrated a same-eye advantage for fearful but not neutral face processing, suggesting that fear processing relied on monocular neurons existing mainly in the subcortex. Experiments 2 and 3 further showed insensitivity to short-wavelength stimuli and a nasal-temporal hemifield asymmetry in fear processing, both of which were functional characteristics of the superior colliculus, a key hub of the subcortical pathway. Furthermore, all three experiments revealed a low spatial frequency selectivity of fear processing, consistent with magnocellular input via subcortical neurons. These results suggest a selective involvement of subcortical structures in fear processing, which, together with the indirect evidence for automatic fear processing, provides a more complete picture of the existence of a subcortical pathway for fear processing in humans. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Transformation of Motion Pattern Selectivity from Retina to Superior Colliculus.

The superior colliculus (SC) is a prominent and conserved visual center in all vertebrates. In mice, the most superficial lamina of the SC is enriched with neurons that are selective for the moving direction of visual stimuli. Here, we study how these direction selective neurons respond to complex motion patterns known as plaids, using two-photon calcium imaging in awake male and female mice. The plaid pattern consists of two superimposed sinusoidal gratings moving in different directions, giving an apparent pattern direction that lies between the directions of the two component gratings. Most direction selective neurons in the mouse SC respond robustly to the plaids and show a high selectivity for the moving direction of the plaid pattern but not of its components. Pattern motion selectivity is seen in both excitatory and inhibitory SC neurons and is especially prevalent in response to plaids with large cross angles between the two component gratings. However, retinal inputs to the SC are ambiguous in their selectivity to pattern versus component motion. Modeling suggests that pattern motion selectivity in the SC can arise from a nonlinear transformation of converging retinal inputs. In contrast, the prevalence of pattern motion selective neurons is not seen in the primary visual cortex (V1). These results demonstrate an interesting difference between the SC and V1 in motion processing and reveal the SC as an important site for encoding pattern motion.

Stimulus-dependent differences in cortical versus subcortical contributions to visual detection in mice.

The primary visual cortex (V1) and the superior colliculus (SC) both occupy stations early in the processing of visual information. They have long been thought to perform distinct functions, with the V1 supporting the perception of visual features and the SC regulating orienting to visual inputs. However, growing evidence suggests that the SC supports the perception of many of the same visual features traditionally associated with the V1. To distinguish V1 and SC contributions to visual processing, it is critical to determine whether both areas causally contribute to the detection of specific visual stimuli. Here, mice reported changes in visual contrast or luminance near their perceptual threshold while white noise patterns of optogenetic stimulation were delivered to V1 or SC inhibitory neurons. We then performed a reverse correlation analysis on the optogenetic stimuli to estimate a neuronal-behavioral kernel (NBK), a moment-to-moment estimate of the impact of V1 or SC inhibition on stimulus detection. We show that the earliest moments of stimulus-evoked activity in the SC are critical for the detection of both luminance and contrast changes. Strikingly, there was a robust stimulus-aligned modulation in the V1 contrast-detection NBK but no sign of a comparable modulation for luminance detection. The data suggest that behavioral detection of visual contrast depends on both V1 and SC spiking, whereas mice preferentially use SC activity to detect changes in luminance. Electrophysiological recordings showed that neurons in both the SC and V1 responded strongly to both visual stimulus types, while the reverse correlation analysis reveals when these neuronal signals actually contribute to visually guided behaviors.

The Visual Systems of Zebrafish.

The zebrafish visual system has become a paradigmatic preparation for behavioral and systems neuroscience. Around 40 types of retinal ganglion cells (RGCs) serve as matched filters for stimulus features, including light, optic flow, prey, and objects on a collision course. RGCs distribute their signals via axon collaterals to 12 retinorecipient areas in forebrain and midbrain. The major visuomotor hub, the optic tectum, harbors nine RGC input layers that combine information on multiple features. The retinotopic map in the tectum is locally adapted to visual scene statistics and visual subfield-specific behavioral demands. Tectal projections to premotor centers are topographically organized according to behavioral commands. The known connectivity in more than 20 processing streams allows us to dissect the cellular basis of elementary perceptual and cognitive functions. Visually evoked responses, such as prey capture or loom avoidance, are controlled by dedicated multistation pathways that-at least in the larva-resemble labeled lines. This architecture serves the neuronal code's purpose of driving adaptive behavior.

Light conditions and the evolution of the visual system in birds.

Despite vision being an essential sense for many animals, the intuitively appealing notion that the visual system has been shaped by environmental light conditions is backed by insufficient evidence. Based on a comprehensive phylogenetic comparative analysis of birds, we investigate if exposure to different light conditions might have triggered evolutionary divergence in the visual system through pressures on light sensitivity, visual acuity, and neural processing capacity. Our analyses suggest that birds that have adopted nocturnal habits evolved eyes with larger corneal diameters and, to a lesser extent, longer axial length than diurnal species. However, we found no evidence that sensing and processing organs were selected together, as observed in diurnal birds. Rather than enlarging the processing centers, we found a tendency among nocturnal species to either reduce or maintain the size of the two main brain centers involved in vision-the optic tectum and the wulst. These results suggest a mosaic pattern of evolution, wherein optimization of the eye optics for efficient light capture in nocturnal species may have compromised visual acuity and central processing capacity.

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.