Differential resilience against complete optic nerve transection across visual areas.

From peripersonal space to cognitive maps: An evolutionary perspective.

The frontal eye field (FEF), located in the bank of the arcuate sulcus, has long been associated with the cortical control of eye movements. A classic observation is that saccades can be reliably evoked from the FEF by delivering low-intensity electrical microstimulation. However, several questions remain regarding how microstimulation parameters influence evoked saccades and how population activity in the FEF is decoded by downstream regions to generate a motor command. To address these questions, we used a 16-channel microelectrode array to deliver microstimulation to the FEF of two awake, behaving monkeys. First, we found that larger current intensities were required to evoke changes in saccade direction relative to saccade amplitude when single-site saccades were evoked by stimulating a single contact on the array. Second, when stimulating two contacts simultaneously to investigate how population activity in the FEF is read-out, a new polar average model more accurately predicted the amplitude and direction of dual-site saccades than traditional vector sum and vector average models. Using preexisting data from the superior colliculus (SC), we found that although the polar average model was more accurate at predicting saccade amplitude in the SC, it was no more accurate than traditional models at predicting saccade direction. Finally, when stimulating two contacts simultaneously with unequal current intensities, model accuracy depended on the amplitude of the saccades evoked by stimulating each individual site alone, suggesting that the brain may flexibly combine amplitude and direction information from the FEF to generate saccadic plans.

Neuroinflammation and mononuclear phagocytes in glaucoma: From ocular pathogenesis to central visual pathway involvement - A comprehensive review.

Binocular integration is a well-established feature of neuronal processing in the primary visual cortex, where such integration is thought to first emerge. However, accumulating evidence demonstrates that subcortical retinorecipient nuclei possess sophisticated binocular processing capabilities, with important implications for cortical function, visual behavior, and non-imaging-forming physiology. This review synthesizes our current understanding of the circuit origins and functional relevance of binocular integration and modulation in the dorsal lateral geniculate nucleus, superior colliculus, and other subcortical targets. We describe how the definition of binocularity has evolved beyond simple ocular dominance to encompass diverse modes of neuronal modulation, including facilitation, summation, suppression, and emergent responses. We highlight the prevalence of multiple wiring motifs subserving binocular convergence, including direct retinal inputs, lateral circuits via local interneurons, feedback from cortical or subcortical sources, and indirect relays through intra- or interhemispheric connections. Recent anatomical and functional studies reveal substantial binocular integration despite apparent eye-specific input segregation, with region- and species-specific differences reflecting distinct ethological demands. Finally, elucidation of a critical role for subcortical binocular processing in prey capture and threat responses is expanding our cortex-centric view and revealing new complexity in the regional distribution of visual computations essential for survival behaviors.

Numerous clinical features of Dementia with Lewy Bodies (DLB) are attributed to dysfunction in subcortical anatomy. Despite this, [18F]FDG PET imaging as a diagnostic tool for DLB largely relies on the metabolic signature of the occipital lobe, precuneus, and posterior cingulate cortex. This study aimed to assess subcortical brain metabolism in patients with DLB using [18F]FDG PET imaging. Patients diagnosed with probable DLB were included from both a prospectively maintained regional database (n = 33), and the ADNI database (n = 43). Using statistical parametric mapping (SPM) analysis, metabolic activity was compared with a cohort of subjects exhibiting normal brain metabolism (n = 19). A sub-analysis was conducted with disease progression included as a covariate. Hypermetabolism was observed in various subcortical regions, notably in the dentate nucleus, anterolateral thalamus, and regions of the superior cerebellar peduncle. Increased metabolism was also detected in the mesencephalic tectum, likely representing heightened activity in the superior colliculus. All findings were reproduced in the ADNI cohort and were found to be dependent on the DLB disease stage. Additionally, the well-established cortical hypometabolic signature of DLB pathology was evident, validating our methods and findings. Increased metabolic activity is evident in a variety of brainstem, cerebellar, and subcortical regions in patients with DLB. The dentatorubrothalamic tract, in particular, emerges as a structure of interest that connects these structures and potentially helps in understanding DLB pathophysiology. Correction for disease stage eliminated this pattern, suggesting a driver associated with disease progression.

Visual impairment is one of the most common and clinically salient manifestations of Multiple Sclerosis (MS), yet pathology across visual system structures remains incompletely defined. Although MS pathology has been extensively studied in the optic nerve, lateral geniculate nucleus, and visual cortex, involvement of the superior colliculus (SC), a key hub for visual processing, has not been systematically investigated. Here, we combined human postmortem tissue analysis with functional assessment and spatial mapping in the MS-relevant cuprizone (CPZ) mouse model to define how demyelination and secondary injury are organized within the SC. Postmortem SC tissue from donors with MS revealed myelin loss, including focal demyelinated lesions. In mice, CPZ treatment impaired visual function and induced widespread demyelination across SC layers, without detectable neuronal cell loss or axonal degeneration. Although diffuse demyelination was accompanied by widespread microgliosis characteristic of CPZ, atlas-based mapping uncovered a previously unrecognized spatial organization: a discrete high-microgliosis compartment that emerged in every CPZ-treated SC with strikingly stereotyped location and shape. This compartment did not correspond to canonical SC maps and was not explained by baseline differences in microglia or myelin or by variability in demyelination severity following CPZ. Instead, regions with elevated microgliosis showed a marked increase in synaptic elimination, suggesting that secondary synaptic pathology may contribute to the spatial organization of microgliosis beyond diffuse myelin loss alone. Prolonged CPZ exposure expanded the compartment in a stereotyped pattern, whereas CPZ withdrawal produced spatially ordered partial resolution while leaving a persistent high-microgliosis core concurrent with partial visual recovery. Together, these findings identify the SC as an MS-relevant site of injury and establish the CPZ-treated SC as a reproduciblein vivomodel for studying spatially patterned microglial reactivity, synaptic pathology, and incomplete inflammatory resolution after demyelinating injury.

Rapid detection of looming objects is essential for survival, yet single retinal ganglion cells have receptive fields that are smaller than many behaviorally relevant looming stimuli. This mismatch raises the question of how the retina represents an expanding threat as it moves beyond the receptive field of a single neuron. Here, we show that gap junctions extend looming-related activity across a coupled network of transient OFF-alpha retinal ganglion cells. Using multiscale electrophysiology, genetic and pharmacological perturbations, and behavioral assays, we found that looming stimuli recruit neighboring retinal ganglion cells through electrical synapses. Targeted recordings showed that activation of one transient OFF-alpha cell can prime neighboring cells, allowing them to respond when the expanding edge reaches their receptive fields. Disrupting gap junction coupling reduced retinal population recruitment, altered looming-evoked response patterns in the superior colliculus, and impaired escape behavior, while leaving visual acuity, depth perception intact, and lateral-motion responses intact. These findings show that electrical synapses transform local looming responses in the retina into a coordinated population signal that extends beyond single receptive fields and supports escape behavior.

Addictive substances transform environmental cues into potent conditioned cues through reward-based associative learning. While visual cues are known to amplify drug-seeking behavior and trigger relapse, the neural circuits mediating their motivational salience remain incompletely understood. Here, we identified the superior colliculus (SC) as a critical encoder of drug-related visual information via gating reinstatement through a defined SC-VTA-NAcore pathway. We established a methamphetamine (MA) self-administration model in mice with fiber photometry, optogenetic, and chemogenetic techniques. Using fiber photometry, we discovered that the monosynaptic SC-VTA pathway exhibited selective activation during exposure to drug-paired visual cues, which demonstrated a stable cue encoding. Optogenetic inhibition of SC-VTA projections completely abolished cue-induced reinstatement, while activation potentiated reinstatement. Transsynaptic tracing confirmed a SCGlu+-VTADA+-NAcore circuit. Bidirectional manipulation of this pathway demonstrated its necessity and sufficiency for controlling cue-triggered reinstatement. Our results establish the SC as a sensory-motivational hub that transforms visual drug cues into relapse-promoting signals through a hardwired midbrain circuit. The discovery of this SC-VTA-NAcore pathway provides both a mechanistic framework for understanding cue-driven addiction and concrete targets for interventions.

Baird's beaked whale, a member of the family Ziphiidae, is one of the largest odontocetes, second only in body mass to the sperm whale. Baird's beaked whales are known for their ability to dive to exceptional depths; however, this behavior makes them difficult to observe in their natural habitat and has resulted in major gaps in our understanding of the species. To address part of this gap, this study provides a comprehensive description of the Baird's beaked whale brain using magnetic resonance imaging (MRI). We describe the external and internal neuroanatomy, including sulcal and gyral patterns, and provide quantitative measurements of the cerebral cortex, amygdala, hippocampus, ventricular system, superior and inferior colliculi, cerebellum, the mid-sagittal cross-sectional area of the corpus callosum, the gyrification index, and encephalization quotient. Baird's beaked whale has a brain organization typical of odontocetes, including a large, exceptionally gyrencephalic neocortex. Both the encephalization quotient and the relative cerebellar volume are lower than in delphinids, consistent with findings in other deep-diving cetaceans. These differences may reflect energy allocation strategies related to diving behavior and body size. By contextualizing these traits within a broader mammalian neuroanatomical framework, this study contributes to our understanding of how ecological pressures may shape brain evolution, particularly in rarely-studied cetacean lineages like the Ziphiidae.

Animals use the location of visual stimuli to select appropriate actions, and the upper and lower visual field often carry different ecological and behavioral meaning. In mice, the superior colliculus is a key cen-tral hub that transforms visual input into orienting, defensive, and approach behaviors. Its superficial layers receive retinotopically organized input from the retina and contain genetically defined cell types with distinct downstream projections, including wide-field neurons that project to the lateral posterior thalamus and narrow-field neurons that target the parabigeminal nucleus and deeper collicular layers. These fea-tures raise the question of whether circuits of the superior colliculus are repeated across visual space or ex-hibit visual-field-dependent specializations. Here, we show that the mouse superficial superior colliculus contains visual-field-dependent circuit modules. Dual-color rabies tracing revealed that wide-field and nar-row-field neurons receive input from a largely shared set of brain regions, whereas upper- and lower-field domains differ in how they sample those inputs. Some source regions preferentially innervate one visual-field domain, producing biased regional input strength, while others contain topographically segregated pro-jecting neurons that target upper- or lower-field domains. MAPseq showed that most superficial collicular neurons project to single downstream targets, with upper- and lower-field populations differing in target probability. Two-photon calcium imaging further showed that wide-field neurons in upper- and lower-field domains differ in stimulus selectivity. Together, these findings reveal a visual-field-dependent wiring logic that biases how the superior colliculus samples inputs and routes signals to downstream pathways.

Although predatory behaviors are evolutionarily conserved, they can be enhanced through experience-dependent plasticity. While vibrissal somatosensation is recognized as a key mediator of hunting behavior, the mechanism underlying vibrissal somatosensory-mediated predatory hunting learning remains not yet well understood. In this study, we report that vibrissal tactile input plays an essential role in hunting learning. Activation of the vGlut1+ S1BF–SC pathway is sufficient to evoke predatory hunting, while its inactivation abolished practice-induced behavioral improvements. SC-projecting vGlut1+ S1BF neurons exhibited robust responses to whisker mechanosensory stimulation. Furthermore, hunting training selectively enhanced α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptormediated excitatory transmission in the vGlut1+ S1BF–SC pathway. Together, these data reveal the corticotectal neural circuit from the primary somatosensory cortex to superior colliculus that was specifically engaged in vibrissal somatosensory-mediated hunting learning by strengthening synaptic connections.

Compulsive drug use despite negative consequences is a core addiction feature and key therapeutic target. Animal models utilize footshock to screen for mice exhibiting compulsive-like addiction traits. Following the administration of aversive stimuli, compulsive animals persist in drug-seeking, suggesting that addicted individuals may have impaired innate defensive responses, thereby exacerbating addictive behaviors. However, little is known about the neural mechanisms behind this behavior. The superior colliculus (SC), a multisensory integration hub, plays a crucial regulatory role in innate fear and defense. This study employed an optical intracranial self-stimulation (oICSS) addiction-like model. Using footshock to screen for mice with compulsive-like behavior, fiber photometry recordings revealed significant differences in neuronal activity within the SC. Specifically, SC neurons in compulsive-like mice showed significantly lower responses to footshock stimuli compared to non-compulsive mice. Subsequently, chemogenetic inhibition of SC neuronal activity in non-compulsive mice significantly reduced their resistance to footshock, inducing a compulsive-like state. Conversely, chemogenetic activation of SC neurons in compulsive-like mice significantly decreased their oICSS behavior. These findings indicate that mice exhibiting compulsive-like addiction behavior, identified through footshock, exhibit significant functional abnormalities in SC neurons. The SC is implicated in regulating compulsive addictive behaviors, providing novel insights into the mechanisms of compulsivity and identifying a promising new target for addiction intervention.

Attention distraction mitigates pain, yet its neural basis remains elusive. We established cricket hunting as an attention-demanding paradigm that alleviates acute and chronic pain in male mice. Activity tagging revealed that cricket hunting activated a subset of glutamatergic neurons in the superior colliculus (SC). Selective stimulation of these hunting-activated neurons alleviated chronic hyperalgesia, primarily mediated by their projections to the zona incerta (ZI). Notably, repeated engagement, either through the hunting paradigm or by repeatedly activating hunting-activated SC-ZI projections, induced sustained analgesia (lasting at least 6 hours), linked to potentiated glutamatergic inputs to ZI GABAergic neurons. Furthermore, SC-ZI projections originating from SC neurons expressing tachykinin precursor 1 (Tac1) selectively elevated neuropathic pain thresholds via substance P release and neurokinin 1 (NK1) receptor-dependent excitatory synaptic transmission onto ZI GABAergic neurons. Together, we show that a specific SC-ZI circuit drives attention-induced analgesia, highlighting the SCTac1-ZI pathway as a therapeutic target for chronic pain.

Mammals rely on their senses to establish their position in space. Neural activity in the hippocampus maps position, yet how sensory signals reach the hippocampus remains poorly understood. Here we uncover the visual pathways informing spatial maps in the mouse hippocampus. Hippocampal activity in mice traversing a track in alternating periods of light and darkness revealed two distinct maps, one in light and one in dark. Surprisingly, distinct maps persisted following bilateral ablations of primary visual cortex, indicating that visual signals still reach the hippocampus. Conversely, blocking the ancestral pathway linking superior colliculus to lateral visual cortex markedly reduced the difference between light and dark maps. Thus, this conserved pathway relays visual information to the hippocampus, potentially explaining residual visual navigation in cortically blind humans.

PurposeThis study used functional magnetic resonance imaging (fMRI) to investigate layer-specific deficits in the retino-geniculo-striate pathway and functional alterations in the retino-tectal pathway in adult unilateral amblyopia.MethodsSixteen adult patients (mean age ± SD = 28.4 ± 5.2 years; 9 men and 7 women) with unilateral amblyopia and 12 matched healthy controls (mean age ± SD = 27.1 ± 4.8 years; 7 men and 5 women) underwent 3T fMRI scanning. The lateral geniculate nucleus (LGN) and superior colliculus (SC) were chosen as regions of interest (ROIs) to assess functional status. Responses of the M and P layers were analyzed with general linear models, and stimulus-specific beta values were extracted for quantitative comparison.ResultsA significant interaction between stimulus type and subject group was observed in the LGN P layer but not in the M layer. The P-layer responses to P stimuli were significantly reduced in amblyopic eyes, whereas M responses remained relatively preserved, this reduction may partly reflect reduced effective contrast in the amblyopic eye, and input-level factors cannot be fully excluded. In the SC, fellow eyes showed decreased M responses and a shift toward P-preference, whereas no clear deficits were observed in amblyopic eyes. Moreover, MT responses in both amblyopic and fellow eyes were significantly reduced compared with healthy controls, suggesting broader cortical involvement. However, V1 and V2 responses showed no significant reduction, indicating relatively intact early visual cortex activation.ConclusionsAn fMRI allowed noninvasive segregation of M and P divisions in the LGN of amblyopic adults. Under the current stimulus conditions, amblyopic eyes showed a predominant reduction in LGN responses, whereas fellow eyes exhibited M-function loss and P-preference shift in the SC. Reduced MT responses in both eyes may arise from abnormal binocular integration mechanisms rather than primary dysfunction in V1 or the M pathway. These findings suggest pathway-selective alterations in subcortical visual structures, although contributions from interocular differences in contrast sensitivity warrant further investigation.

Binocular vision requires both eyes to be aligned such that their visual fields overlap. A long-standing premise derived from comparative studies is that the orientation of the orbits determines eye position, and thereby the extension of this overlap, the binocular field. In addition, to produce an accurate neural representation, the binocular field must integrate with the position of retinal high-acuity areas and with the extent of uncrossed retinal projections. It remains unknown, however, whether the binocular field is already formed at the time of eye-opening, as well as when and how it integrates with neuroanatomical visual traits during development. Using the diurnal rodent Octodon degus, a suitable animal model for visual neuroscience, we combined CT-based 3D cranial reconstructions, quantitative measurements of visual-field geometry, whole-mount retinal topography, neural tracing of retinal projections, and behavioral assays to reconstruct the postnatal assembly of the binocular visual system. We show that orbital and ocular orientations shift substantially after birth, broadening the dorsal binocular field; that retinal ganglion cell distributions sharpen into a horizontal visual streak and a defined area centralis; and that ipsilateral projections to the superior colliculus mature in parallel to binocular expansion. These changes coincide with the emergence of binocular-dependent behaviors such as depth discrimination and looming-evoked escape responses. Together, our findings demonstrate that binocular vision emerges through the coordinated alignment of multiple developmental processes across levels of organization.

Understanding drug pharmacokinetics (PK) at its site of action, particularly in the brain, is essential for accurately evaluating therapeutic efficacy and safety. However, conventional PK assessment based on blood measurements often fails to reflect drug dynamics in the central nervous system (CNS). Here, taking the anti-Parkinson's drug safinamide (SAF) as an example, we introduce a real-time in vivo electrochemical sensing strategy with high spatiotemporal resolution, operational simplicity, and excellent reproducibility. Our results reveal that the PK profile of SAF in the substantia nigra (SN) differs markedly from that in plasma, characterized by enhanced brain accumulation and distinct clearance kinetics. By simultaneously monitoring SAF and neuronal activity in the superficial gray layer (SuG) of the superior colliculus (SC), we observed pronounced suppression of neuronal firing at peak SAF levels, followed by gradual recovery during SAF elimination. This tight temporal correlation suggests that transient inhibition of vision-related neuronal activity may be directly associated with SAF concentration at the site. Overall, our study establishes an electrochemical approach enabling rapid, selective, and real-time drug monitoring in the living brain, offering a powerful tool to promote mechanistic studies of CNS drugaction and safety.

Moving backgrounds profoundly impact object perception, a crucial process for parsing complex visual scenes. This motion-induced modulation has traditionally been attributed to visual cortical circuits. However, recent evidence that brainstem activity is also influenced by background motion raises the intriguing question of whether subcortical circuits play a role in this perceptual phenomenon. Here, we demonstrate that inhibitory projections from mouse nucleus of the optic tract (NOT)-a brainstem structure mediating reflexive behaviors-impair superior colliculus (SC)-dependent visual detection during background motion. Specifically, the inhibitory NOT projections to SC are selectively activated by global, but not local, background motion to suppress SC activity. Remarkably, silencing this NOT-SC pathway relieves the suppression of SC activity in such motional context and alleviates the motion-induced impairments in visual detection. Our findings reveal that motion-sensitive brainstem circuits suppress subcortical processing to shape visual perception, underscoring the underappreciated role of the brainstem in visual cognition.

Summary:The superior colliculus (SC) is an ancient visual structure whose principle source of visual drive comes directly from the retina. In primates, however, the SC also receives geniculostriate input from primary visual cortex (V1) via the lateral geniculate nucleus (LGN), making it unclear which pathway normally drives visually evoked spiking. Here we tested whether visually evoked spiking in the primate SC depends on retinal signals routed through LGN and V1, rather than on direct retinal input alone. We recorded from macaque SC neurons before and during reversible inactivation of the ipsilateral LGN and found that LGN inactivation nearly abolished visually evoked spiking. This loss was not due to nonspecific suppression of SC, because saccade-related bursts were spared and was observed across SC layers. Magnocellular-biased stimuli, designed to reveal any potential direct retinal drive, failed to produce visually evoked spiking during LGN inactivation. Interhemispheric inhibition (i.e., a “Sprague effect”) was ruled out, because contralateral SC silencing during LGN inactivation did not restore SC visual responses. Consistent with a geniculostriate input route to SC, V1 inactivation also reduced SC visual responses, with effects proportional to the overlap between the V1-induced scotoma and the stimulus representation. Together, these results show that visually evoked neural responses in primate SC depend on retinal signals routed through LGN and V1, and that direct retinotectal input is insufficient to drive SC spiking in the absence of geniculostriate input. These findings revise current models of visual drive to the primate SC and constrain theories of SC-dependent visual behavior.