A non-canonical visual cortical-entorhinal pathway contributes to spatial navigation.

Visual information is important for accurate spatial coding and memory-guided navigation. As a crucial area for spatial cognition, the medial entorhinal cortex (MEC) harbors diverse spatially tuned cells and functions as the major gateway relaying sensory inputs to the hippocampus containing place cells. However, how visual information enters the MEC has not been fully understood. Here, we identify a pathway originating in the secondary visual cortex (V2) and directly targeting MEC layer 5a (L5a). L5a neurons served as a network hub for visual processing in the MEC by routing visual inputs from multiple V2 areas to other local neurons and hippocampal CA1. Interrupting this pathway severely impaired visual stimulus-evoked neural activity in the MEC and performance of mice in navigation tasks. These observations reveal a visual cortical-entorhinal pathway highlighting the role of MEC L5a in sensory information transmission, a function typically attributed to MEC superficial layers before.

Asymmetric Activation of ON and OFF Pathways in the Degenerated Retina.

Retinal prosthetics are one of the leading therapeutic strategies to restore lost vision in patients with retinitis pigmentosa and age-related macular degeneration. Much work has described patterns of spiking in retinal ganglion cells (RGCs) in response to electrical stimulation, but less work has examined the underlying retinal circuitry that is activated by electrical stimulation to drive these responses. Surprisingly, little is known about the role of inhibition in generating electrical responses or how inhibition might be altered during degeneration. Using whole-cell voltage-clamp recordings during subretinal electrical stimulation in the rd10 and wild-type (wt) retina, we found electrically evoked synaptic inputs differed between ON and OFF RGC populations, with ON cells receiving mostly excitation and OFF cells receiving mostly inhibition and very little excitation. We found that the inhibition of OFF bipolar cells limits excitation in OFF RGCs, and a majority of both pre- and postsynaptic inhibition in the OFF pathway arises from glycinergic amacrine cells, and the stimulation of the ON pathway contributes to inhibitory inputs to the RGC. We also show that this presynaptic inhibition in the OFF pathway is greater in the rd10 retina, compared with that in the wt retina.

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.

Cerebral versus cortical visual impairment: eliminating the conflict and renewing the terminology.

The inconsistency in terminology for Cortical Visual Impairment or Cerebral Visual Impairment presents challenges: (1) different levels of changes in visual pathway and other cerebral areas do not allow discrimination; (2) different visual and oculomotor aspects are not adequately considered. We open a debate to consider a more appropriate diagnosis.

Neuroplasticity of visual brain network induced by hypoxia.

The effects of hypoxia on brain function remain largely unknown. This study aimed to clarify this issue by visual-stimulated functional magnetic resonance imaging design. Twenty-three college students with a 30-d high-altitude exposure were tested before, 1 week and 3 months after returning to sea level. Brain functional magnetic resonance imaging and retinal electroretinogram were acquired. One week after returning to sea level, decreased blood oxygenation level dependent in the right lingual gyrus accompanied with increased blood oxygenation level dependent in the frontal cortex and insular cortex, and decreased amplitude of electroretinogram a-wave in right eye; moreover, the bilateral lingual gyri showed increased functional connectivity within the dorsal visual stream pathway, and the blood oxygenation level dependent signals in the right lingual gyrus showed positive correlation with right retinal electroretinogram a-wave. Three months after returning to sea level, the blood oxygenation level dependent signals recovered to normal level, while intensively increased blood oxygenation level dependent signals in a broad of brain regions and decreased retinal electroretinogram were also existed. In conclusion, hypoxic exposure has long-term effects on visual cortex, and the impaired retinal electroretinogram may contribute to it. The increased functional connectivity of dorsal stream may compensate for the decreased function of retinal photoreceptor cells to maintain normal visual function.

Spiking activity in the visual thalamus is coupled to pupil dynamics across temporal scales.

The processing of sensory information, even at early stages, is influenced by the internal state of the animal. Internal states, such as arousal, are often characterized by relating neural activity to a single "level" of arousal, defined by a behavioral indicator such as pupil size. In this study, we expand the understanding of arousal-related modulations in sensory systems by uncovering multiple timescales of pupil dynamics and their relationship to neural activity. Specifically, we observed a robust coupling between spiking activity in the mouse dorsolateral geniculate nucleus (dLGN) of the thalamus and pupil dynamics across timescales spanning a few seconds to several minutes. Throughout all these timescales, 2 distinct spiking modes-individual tonic spikes and tightly clustered bursts of spikes-preferred opposite phases of pupil dynamics. This multi-scale coupling reveals modulations distinct from those captured by pupil size per se, locomotion, and eye movements. Furthermore, coupling persisted even during viewing of a naturalistic movie, where it contributed to differences in the encoding of visual information. We conclude that dLGN spiking activity is under the simultaneous influence of multiple arousal-related processes associated with pupil dynamics occurring over a broad range of timescales.

Nonuniform and pathway-specific laminar processing of spatial frequencies in the primary visual cortex of primates.

The neocortex comprises six cortical layers that play a crucial role in information processing; however, it remains unclear whether laminar processing is consistent across all regions within a single cortex. In this study, we demonstrate diverse laminar response patterns in the primary visual cortex (V1) of three male macaque monkeys when exposed to visual stimuli at different spatial frequencies (SFs). These response patterns can be categorized into two groups. One group exhibit suppressed responses in the output layers for all SFs, while the other type shows amplified responses specifically at high SFs. Further analysis suggests that both magnocellular (M) and parvocellular (P) pathways contribute to the suppressive effect through feedforward mechanisms, whereas amplification is specific to local recurrent mechanisms within the parvocellular pathway. These findings highlight the non-uniform distribution of neural mechanisms involved in laminar processing and emphasize how pathway-specific amplification selectively enhances representations of high-SF information in primate V1.

Predicting high-level visual areas in the absence of task fMRI.

The ventral visual stream is organized into units, or functional regions of interest (fROIs), specialized for processing high-level visual categories. Task-based fMRI scans ("localizers") are typically used to identify each individual's nuanced set of fROIs. The unique landscape of an individual's functional activation may rely in large part on their specialized connectivity patterns; recent studies corroborate this by showing that connectivity can predict individual differences in neural responses. We focus on the ventral visual stream and ask: how well can an individual's resting state functional connectivity localize their fROIs for face, body, scene, and object perception? And are the neural processors for any particular visual category better predicted by connectivity than others, suggesting a tighter mechanistic relationship between connectivity and function? We found, among 18 fROIs predicted from connectivity for each subject, all but one were selective for their preferred visual category. Defining an individual's fROIs based on their connectivity patterns yielded regions that were more selective than regions identified from previous studies or atlases in nearly all cases. Overall, we found that in the absence of a domain-specific localizer task, a 10-min resting state scan can be reliably used for defining these fROIs.

Two what, two where, visual cortical streams in humans.

ROLLS, E. T. Two What, Two Where, Visual Cortical Streams in Humans. NEUROSCI BIOBEHAV REV 2024. Recent cortical connectivity investigations lead to new concepts about 'What' and 'Where' visual cortical streams in humans, and how they connect to other cortical systems. A ventrolateral 'What' visual stream leads to the inferior temporal visual cortex for object and face identity, and provides 'What' information to the hippocampal episodic memory system, the anterior temporal lobe semantic system, and the orbitofrontal cortex emotion system. A superior temporal sulcus (STS) 'What' visual stream utilising connectivity from the temporal and parietal visual cortex responds to moving objects and faces, and face expression, and connects to the orbitofrontal cortex for emotion and social behaviour. A ventromedial 'Where' visual stream builds feature combinations for scenes, and provides 'Where' inputs via the parahippocampal scene area to the hippocampal episodic memory system that are also useful for landmark-based navigation. The dorsal 'Where' visual pathway to the parietal cortex provides for actions in space, but also provides coordinate transforms to provide inputs to the parahippocampal scene area for self-motion update of locations in scenes in the dark or when the view is obscured.

Galectin-3 Plays a Role in Neuroinflammation in the Visual Pathway in Experimental Optic Neuritis.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) featuring numerous neuropathologies, including optic neuritis (ON) in some patients. However, the molecular mechanisms of ON remain unknown. Galectins, ß-galactoside-binding lectins, are involved in various pathophysiological processes. We previously showed that galectin-3 (gal-3) is associated with the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. In the current study, we investigated the expression of gal-3 in the visual pathway in EAE mice to clarify its role in the pathogenesis of ON. Immunohistochemical analysis revealed upregulation of gal-3 in the visual pathway of the EAE mice during the peak stage of the disease, compared with naïve and EAE mice during the chronic stage. Gal-3 was detected mainly in microglia/macrophages and astrocytes in the visual pathway in EAE mice. In addition, gal-3+/Iba-1+ cells, identified as phagocytic by immunostaining for cathepsin D, accumulated in demyelinating lesions in the visual pathway during the peak disease stage of EAE. Moreover, NLRP3 expression was detected in most gal-3+/Iba-1+ cells. These results strongly suggest that gal-3 regulates NLRP3 signaling in microglia/macrophages and neuroinflammatory demyelination in ON. In astrocytes, gal-3 was expressed from the peak to the chronic disease stages. Taken together, our findings suggest a critical role of gal-3 in the pathogenesis of ON. Thus, gal-3 in glial cells may serve as a potential therapeutic target for ON.

A histological and diceCT-derived 3D reconstruction of the avian visual thalamofugal pathway.

Amniotes feature two principal visual processing systems: the tectofugal and thalamofugal pathways. In most mammals, the thalamofugal pathway predominates, routing retinal afferents through the dorsolateral geniculate complex to the visual cortex. In most birds, the thalamofugal pathway often plays the lesser role with retinal afferents projecting to the principal optic thalami, a complex of several nuclei that resides in the dorsal thalamus. This thalamic complex sends projections to a forebrain structure called the Wulst, the terminus of the thalamofugal visual system. The thalamofugal pathway in birds serves many functions such as pattern discrimination, spatial memory, and navigation/migration. A comprehensive analysis of avian species has unveiled diverse subdivisions within the thalamic and forebrain structures, contingent on species, age, and techniques utilized. In this study, we documented the thalamofugal system in three dimensions by integrating histological and contrast-enhanced computed tomography imaging of the avian brain. Sections of two-week-old chick brains were cut in either coronal, sagittal, or horizontal planes and stained with Nissl and either Gallyas silver or Luxol Fast Blue. The thalamic principal optic complex and pallial Wulst were subdivided on the basis of cell and fiber density. Additionally, we utilized the technique of diffusible iodine-based contrast-enhanced computed tomography (diceCT) on a 5-week-old chick brain, and right eyeball. By merging diceCT data, stained histological sections, and information from the existing literature, a comprehensive three-dimensional model of the avian thalamofugal pathway was constructed. The use of a 3D model provides a clearer understanding of the structural and spatial organization of the thalamofugal system. The ability to integrate histochemical sections with diceCT 3D modeling is critical to better understanding the anatomical and physiologic organization of complex pathways such as the thalamofugal visual system.

How Does the Inner Retinal Network Shape the Ganglion Cells Receptive Field? A Computational Study.

We consider a model of basic inner retinal connectivity where bipolar and amacrine cells interconnect and both cell types project onto ganglion cells, modulating their response output to the brain visual areas. We derive an analytical formula for the spatiotemporal response of retinal ganglion cells to stimuli, taking into account the effects of amacrine cells inhibition. This analysis reveals two important functional parameters of the network: (1) the intensity of the interactions between bipolar and amacrine cells and (2) the characteristic timescale of these responses. Both parameters have a profound combined impact on the spatiotemporal features of retinal ganglion cells' responses to light. The validity of the model is confirmed by faithfully reproducing pharmacogenetic experimental results obtained by stimulating excitatory DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) expressed on ganglion cells and amacrine cells' subclasses, thereby modifying the inner retinal network activity to visual stimuli in a complex, entangled manner. Our mathematical model allows us to explore and decipher these complex effects in a manner that would not be feasible experimentally and provides novel insights in retinal dynamics.

Visual omitted stimulus potentials are not retinotopic.

Omitted stimulus potentials (OSPs) are elicited in response to the omission of expected stimuli and are thought to reflect prediction errors. If prediction errors are signaled in the sensory cortex, OSPs are expected to be generated in the sensory cortex. The present study investigated the involvement of the early visual cortex in the generation of OSPs by testing whether omitted visual stimuli elicit brain responses in a spatially specific manner. Checkerboard pattern stimuli were presented alternately in the upper and lower visual fields, and the stimuli were omitted in 10 % of the trials. Event-related potentials were recorded from 33 participants. While a retinotopic C1 component was evoked by real visual stimuli, omitted stimuli did not produce any response reflecting retinotopy but did elicit a visual mismatch negativity, which was larger for omitted stimuli expected in the lower visual field than for those in the upper visual field. These results suggest that omitted visual stimuli are processed in a different pathway than actual stimuli.

Increased glutamatergic neurotransmission between the retinohypothalamic tract and the suprachiasmatic nucleus of old mice.

Circadian rhythms synchronize to light through the retinohypothalamic tract (RHT), which is a bundle of axons coming from melanopsin retinal ganglion cells, whose synaptic terminals release glutamate to the ventral suprachiasmatic nucleus (SCN). Activation of AMPA-kainate and NMDA postsynaptic receptors elicits the increase in intracellular calcium required for triggering the signaling cascade that ends in phase shifts. During aging, there is a decline in the synchronization of circadian rhythms to light. With electrophysiological (whole-cell patch-clamp) and immunohistochemical assays, in this work, we studied pre- and postsynaptic properties between the RHT and ventral SCN neurons in young adult (P90-120) and old (P540-650) C57BL/6J mice. Incremental stimulation intensities (applied on the optic chiasm) induced much lesser AMPA-kainate postsynaptic responses in old animals, implying a lower recruitment of RHT fibers. Conversely, a higher proportion of old SCN neurons exhibited synaptic facilitation, and variance-mean analysis indicated an increase in the probability of release in RHT terminals. Moreover, both spontaneous and miniature postsynaptic events displayed larger amplitudes in neurons from aged mice, whereas analysis of the NMDA and AMPA-kainate components (evoked by RHT electrical stimulation) disclosed no difference between the two ages studied. Immunohistochemistry revealed a bigger size in the puncta of vGluT2, GluN2B, and GluN2A of elderly animals, and the number of immunopositive particles was increased, but that of PSD-95 was reduced. All these synaptic adaptations could be part of compensatory mechanisms in the glutamatergic signaling to ameliorate the loss of RHT terminals in old animals.

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.

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.

Parallel Streams of Direct Corticogeniculate Feedback from Mid-level Extrastriate Cortex in the Macaque Monkey.

First-order thalamic nuclei receive feedforward signals from peripheral receptors and relay these signals to primary sensory cortex. Primary sensory cortex, in turn, provides reciprocal feedback to first-order thalamus. Because the vast majority of sensory thalamocortical inputs target primary sensory cortex, their complementary corticothalamic neurons are assumed to be similarly restricted to primary sensory cortex. We upend this assumption by characterizing morphologically diverse neurons in multiple mid-level visual cortical areas of the primate (Macaca mulatta) brain that provide direct feedback to the primary visual thalamus, the dorsal lateral geniculate nucleus (LGN). Although the majority of geniculocortical neurons project to primary visual cortex (V1), a minority, located mainly in the koniocellular LGN layers, provide direct input to extrastriate visual cortex. These "V1-bypassing" projections may be implicated in blindsight. We hypothesized that geniculocortical inputs directly targeting extrastriate cortex should be complemented by reciprocal corticogeniculate circuits. Using virus-mediated circuit tracing, we discovered corticogeniculate neurons throughout three mid-level extrastriate areas: MT, MST, and V4. Quantitative morphological analyses revealed nonuniform distributions of unique cell types across areas. Many extrastriate corticogeniculate neurons had spiny stellate morphology, suggesting possible targeting of koniocellular LGN layers. Importantly though, multiple morphological types were observed across areas. Such morphological diversity could suggest parallel streams of V1-bypassing corticogeniculate feedback at multiple stages of the visual processing hierarchy. Furthermore, the presence of corticogeniculate neurons across visual cortex necessitates a reevaluation of the LGN as a hub for visual information rather than a simple relay.

A clinico-anatomical dissection of the magnocellular and parvocellular pathways in a patient with the Riddoch syndrome.

KEY MESSAGE: The Riddoch syndrome is thought to be caused by damage to the primary visual cortex (V1), usually following a vascular event. This study shows that damage to the anatomical input to V1, i.e., the optic radiations, can result in selective visual deficits that mimic the Riddoch syndrome. The results also highlight the differential susceptibility of the magnocellular and parvocellular visual systems to injury. Overall, this study offers new insights that will improve our understanding of the impact of brain injury and neurosurgery on the visual pathways. The Riddoch syndrome, characterised by the ability to perceive, consciously, moving visual stimuli but not static ones, has been associated with lesions of primary visual cortex (V1). We present here the case of patient YL who, after a tumour resection surgery that spared his V1, nevertheless showed symptoms of the Riddoch syndrome. Based on our testing, we postulated that the magnocellular (M) and parvocellular (P) inputs to his V1 may be differentially affected. In a first experiment, YL was presented with static and moving checkerboards in his blind field while undergoing multimodal magnetic resonance imaging (MRI), including structural, functional, and diffusion, acquired at 3 T. In a second experiment, we assessed YL's neural responses to M and P visual stimuli using psychophysics and high-resolution fMRI acquired at 7 T. YL's optic radiations were partially damaged but not severed. We found extensive activity in his visual cortex for moving, but not static, visual stimuli, while our psychophysical tests revealed that only low-spatial frequency moving checkerboards were perceived. High-resolution fMRI revealed strong responses in YL's V1 to M stimuli and very weak ones to P stimuli, indicating a functional P lesion affecting V1. In addition, YL frequently reported seeing moving stimuli and discriminating their direction of motion in the absence of visual stimulation, suggesting that he was experiencing visual hallucinations. Overall, this study highlights the possibility of a selective loss of P inputs to V1 resulting in the Riddoch syndrome and in hallucinations of visual motion.