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.

Pathways from the superior colliculus and the nucleus of the optic tract to the posterior parietal cortex in macaque monkeys: Functional frameworks for representation updating and online movement guidance.

The posterior parietal cortex (PPC) integrates multisensory and motor-related information for generating and updating body representations and movement plans. We used retrograde transneuronal transfer of rabies virus combined with a conventional tracer in macaque monkeys to identify direct and disynaptic pathways to the arm-related rostral medial intraparietal area (MIP), the ventral lateral intraparietal area (LIPv), belonging to the parietal eye field, and the pursuit-related lateral subdivision of the medial superior temporal area (MSTl). We found that these areas receive major disynaptic pathways via the thalamus from the nucleus of the optic tract (NOT) and the superior colliculus (SC), mainly ipsilaterally. NOT pathways, targeting MSTl most prominently, serve to process the sensory consequences of slow eye movements for which the NOT is the key sensorimotor interface. They potentially contribute to the directional asymmetry of the pursuit and optokinetic systems. MSTl and LIPv receive feedforward inputs from SC visual layers, which are potential correlates for fast detection of motion, perceptual saccadic suppression and visual spatial attention. MSTl is the target of efference copy pathways from saccade- and head-related compartments of SC motor layers and head-related reticulospinal neurons. They are potential sources of extraretinal signals related to eye and head movement in MSTl visual-tracking neurons. LIPv and rostral MIP receive efference copy pathways from all SC motor layers, providing online estimates of eye, head and arm movements. Our findings have important implications for understanding the role of the PPC in representation updating, internal models for online movement guidance, eye-hand coordination and optic ataxia.

The Human Visual Pathway Communicates Directly With the Subarachnoid Space.

Purpose: Explore in vivo whether there is direct communication between the cerebrospinal fluid (CSF) and extravascular compartment of human visual pathway structures. Methods: A prospective and observational study included 10 subjects who underwent intrathecal gadolinium-enhanced magnetic resonance imaging (MRI) for suspected CSF circulation disorder, but with a negative result and with no known ophthalmic diseases. After precontrast T1-weighted MRI, 0.5 mL of gadobutrol (Gadovist, 1.0 mmol/mL) was injected intrathecally. Gadobutrol distributes in the extravascular space, and served as a CSF tracer. Consecutive MRI scans were obtained throughout 24 to 48 hours. To assess gadobutrol contrast enrichment, regions of interest (ROIs) were placed at multiple locations along the visual pathway, from the primary visual cortex to the eye's vitreous body. CSF tracer dependent T1 signal was measured in each ROI. A linear mixed-model was used for statistical analyses. Results: CSF tracer enrichment was found within the optic nerve, optic chiasm, optic tract, and primary visual cortex (P < 0.001). Peak tracer enrichment in the visual pathway generally occurred after 24 hours and was preceded by peak enhancement in the prechiasmatic cistern after 4 to 6 hours. Conclusions: The results indicate direct communication between CSF of subarachnoid space and the extravascular space of the human visual pathway. Extravascular entry of the CSF tracer is a prerequisite for a glymphatic system, the present findings may suggest its presence. The existence of a glymphatic system in the human visual pathway could bring novel perspectives on the pathophysiology and treatment of ophthalmic diseases.

Rapid changes in tissue mechanics regulate cell behaviour in the developing embryonic brain.

Tissue mechanics is important for development; however, the spatio-temporal dynamics of in vivo tissue stiffness is still poorly understood. We here developed tiv-AFM, combining time-lapse in vivo atomic force microscopy with upright fluorescence imaging of embryonic tissue, to show that during development local tissue stiffness changes significantly within tens of minutes. Within this time frame, a stiffness gradient arose in the developing Xenopus brain, and retinal ganglion cell axons turned to follow this gradient. Changes in local tissue stiffness were largely governed by cell proliferation, as perturbation of mitosis diminished both the stiffness gradient and the caudal turn of axons found in control brains. Hence, we identified a close relationship between the dynamics of tissue mechanics and developmental processes, underpinning the importance of time-resolved stiffness measurements.

Projections of three subcortical visual centers to marmoset lateral geniculate nucleus.

The dorsal lateral geniculate nucleus receives projections from visuotopically organized subcortical nuclei, in addition to inputs from the retina, visual cortices, and the thalamic reticular nucleus. Here, we study subcortical projections to the geniculate from the superior colliculus (SC) and parabigeminal nucleus (PBG) in the midbrain, and the nucleus of the optic tract (NOT) in the pretectum of marmosets. Marmosets are New World diurnal foveate monkeys, and are an increasingly popular model for studying the primate visual system. Furthermore, the koniocellular geniculate layers in marmosets, unlike those in the geniculate of commonly studied diurnal Old World monkeys, are well differentiated from the parvocellular and magnocellular layers. Thus, in the present study, we have made small iontophoretic injections of the retrograde tracer microruby, targeted to the koniocellular layers in the geniculates of four marmosets. We found direct projections from the ipsilateral SC, PBG, and NOT to the koniocellular geniculate layers. The distribution of retrogradely labeled cells in the superficial, visual layers of SC is consistent with the idea that projections from the SC to the koniocellular layers are visuotopically organized. A little over 20 years ago, Vivien Casagrande () introduced the idea that koniocellular geniculate layers (rather than the parvocellular and magnocellular layers) are principal targets of visuotopically organized subcortical nuclei. Our results add to subsequent evidence assembled by Casagrande and others in favor of this hypothesis.

Genetic access to neurons in the accessory optic system reveals a role for Sema6A in midbrain circuitry mediating motion perception.

The accessory optic system (AOS) detects retinal image slip and reports it to the oculomotor system for reflexive image stabilization. Here, we characterize two Cre lines that permit genetic access to AOS circuits responding to vertical motion. The first (Pcdh9-Cre) labels only one of the four subtypes of ON direction-selective retinal ganglion cells (ON-DS RGCs), those preferring ventral retinal motion. Their axons diverge from the optic tract just behind the chiasm and selectively innervate the medial terminal nucleus (MTN) of the AOS. Unlike most RGC subtypes examined, they survive after optic nerve crush. The second Cre-driver line (Pdzk1ip1-Cre) labels postsynaptic neurons in the MTN. These project predominantly to the other major terminal nucleus of the AOS, the nucleus of the optic tract (NOT). We find that the transmembrane protein semaphorin 6A (Sema6A) is required for the formation of axonal projections from the MTN to the NOT, just as it is for the retinal innervation of the MTN. These new tools permit manipulation of specific circuits in the AOS and show that Sema6A is required for establishing AOS connections in multiple locations.

Refinement of Spatial Receptive Fields in the Developing Mouse Lateral Geniculate Nucleus Is Coordinated with Excitatory and Inhibitory Remodeling.

Receptive field properties of individual visual neurons are dictated by the precise patterns of synaptic connections they receive, including the arrangement of inputs in visual space and features such as polarity (On vs Off). The inputs from the retina to the lateral geniculate nucleus (LGN) in the mouse undergo significant refinement during development. However, it is unknown how this refinement corresponds to the establishment of functional visual response properties. Here we conducted in vivo and in vitro recordings in the mouse LGN, beginning just after natural eye opening, to determine how receptive fields develop as excitatory and feedforward inhibitory retinal afferents refine. Experiments used both male and female subjects. For in vivo assessment of receptive fields, we performed multisite extracellular recordings in awake mice. Spatial receptive fields at eye-opening were >2 times larger than in adulthood, and decreased in size over the subsequent week. This topographic refinement was accompanied by other spatial changes, such as a decrease in spot size preference and an increase in surround suppression. Notably, the degree of specificity in terms of On/Off and sustained/transient responses appeared to be established already at eye opening and did not change. We performed in vitro recordings of the synaptic responses evoked by optic tract stimulation across the same time period. These recordings revealed a pairing of decreased excitatory and increased feedforward inhibitory convergence, providing a potential mechanism to explain the spatial receptive field refinement.SIGNIFICANCE STATEMENT The development of precise patterns of retinogeniculate connectivity has been a powerful model system for understanding the mechanisms underlying the activity-dependent refinement of sensory systems. Here we link the maturation of spatial receptive field properties in the lateral geniculate nucleus (LGN) to the remodeling of retinal and inhibitory feedforward convergence onto LGN neurons. These findings should thus provide a starting point for testing the cell type-specific plasticity mechanisms that lead to refinement of different excitatory and inhibitory inputs, and for determining the effect of these mechanisms on the establishment of mature receptive fields in the LGN.

[Neuroanatomy of the Visual Pathway]. / Neuroanatomie der Sehbahn.

Precise knowledge of the neuroanatomy of the visual system including the perception of visual stimuli in the retina, the transmission of visual information to other areas of the central nervous system and the processing of visual information, are most important for diagnostics of diseases, which are affecting this system. Such knowledge allows, even after just a clinical examination, already a quite precise localisation of potential lesions. The aim of this article is to illustrate the neuroanatomy of the visual system with the focus on the visual pathway and the processing of visual information. Next to the main visual pathway, also other retinofugal projections are discussed. Domains, which are important for the oculomotor system, are discussed in another article in this edition of the journal.

[Neuroanatomy of the Oculomotor System]. / Neuroanatomie des okulomotorischen Systems.

After just a clinical examination, the experienced neurologist can assign specific symptoms quite precisely to distinct lesions within the brain and other parts of the nervous system, on the basis of his neuroanatomical knowledge. This also holds true for lesions affecting the oculomotor system. The aim of this article is to give a comprehensive overview of the neuroanatomical basis of the oculomotor system, in order to facilitate the precise spatial assignment of potential lesions affecting the control of eye movements. After a brief introduction, the components of the system are discussed, including the extraocular muscles and their innervating nerves. The following section will then cover the control of eye movements and will specifically address distinct patterns of eye movements and areas within the central nervous system controlling these. This article also gives a brief overview of the intraocular muscles and their control.

GnRH suppresses excitability of visual processing neurons in the optic tectum.

Animals change their behavior in response to sensory cues in the environment as well as their physiological status. For example, it is generally accepted that their sexual behavior is modulated according to seasonal environmental changes or the individual's maturational/reproductive status, and neuropeptides have been suggested to play important roles in this process. Some behavioral modulation arises from neuropeptide modulation of sensory information processing in the central nervous system, but the neural mechanisms still remain unknown. Here we focused on the neural basis of neuropeptide modulation of visual processing in vertebrates. The terminal nerve neurons that contain gonadotropin-releasing hormone 3 (TN-GnRH3 neurons) are suggested to modulate reproductive behavior and have massive projections to the optic tectum (OT), which plays an important role in visual processing. In the present study, to examine whether GnRH3 modulates retino-tectal neurotransmission in the OT, we analyzed the effect of GnRH3 electrophysiologically and morphologically. We found that field potentials evoked by optic tract fiber stimulation, which represent retino-tectal neurotransmission, were modulated postsynaptically by GnRH3. Whole cell recording from postsynaptic neurons in the retino-tectal pathway suggested that GnRH3 activates large-conductance Ca(2+)-activated K(+) (BK) channels and thereby suppresses membrane excitability. Furthermore, our improved morphological analysis using fluorescently labeled GnRH peptides showed that GnRH receptors are localized mainly around the cell bodies of postsynaptic neurons. Our results indicate that TN-GnRH3 neurons modulate retino-tectal neurotransmission by suppressing the excitability of projection neurons in the OT, which underlies the neuromodulation of behaviorally relevant visual information processing by the neuropeptide GnRH3.

Lateral geniculate body evoked potentials elicited by visual and electrical stimulation.

PURPOSE: Blind individuals who have photoreceptor loss are known to perceive phosphenes with electrical stimulation of their remaining retinal ganglion cells. We proposed that implantable lateral geniculate body (LGB) stimulus electrode arrays could be used to generate phosphene vision. We attempted to refine the basic reference of the electrical evoked potentials (EEPs) elicited by microelectrical stimulations of the optic nerve, optic tract and LGB of a domestic pig, and then compared it to visual evoked potentials (VEPs) elicited by short-flash stimuli. METHODS: For visual function measurement, VEPs in response to short-flash stimuli on the left eye of the domestic pig were assessed over the visual cortex at position Oz with the reference electrode at Fz. After anesthesia, linearly configured platinum wire electrodes were inserted into the optic nerve, optic track and LGB. To determine the optimal stimulus current, EEPs were recorded repeatedly with controlling the pulse and power. The threshold of current and charge density to elicit EEPs at 0.3 ms pulse duration was about ±10 µA. RESULTS: Our experimental results showed that visual cortex activity can be effectively evoked by stimulation of the optic nerve, optic tract and LGB using penetrating electrodes. The latency of P1 was more shortened as the electrical stimulation was closer to LGB. The EEPs of two-channel in the visual cortex demonstrated a similar pattern with stimulation of different spots of the stimulating electrodes. We found that the LGB-stimulated EEP pattern was very similar to the simultaneously generated VEP on the control side, although implicit time deferred. CONCLUSIONS: EEPs and VEPs derived from visual-system stimulation were compared. The LGB-stimulated EEP wave demonstrated a similar pattern to the VEP waveform except implicit time, indicating prosthetic-based electrical stimulation of the LGB could be utilized for the blind to perceive vision of phosphenes.

Nuclei-specific differences in nerve terminal distribution, morphology, and development in mouse visual thalamus.

BACKGROUND: Mouse visual thalamus has emerged as a powerful model for understanding the mechanisms underlying neural circuit formation and function. Three distinct nuclei within mouse thalamus receive retinal input, the dorsal lateral geniculate nucleus (dLGN), the ventral lateral geniculate nucleus (vLGN), and the intergeniculate nucleus (IGL). However, in each of these nuclei, retinal inputs are vastly outnumbered by nonretinal inputs that arise from cortical and subcortical sources. Although retinal and nonretinal terminals associated within dLGN circuitry have been well characterized, we know little about nerve terminal organization, distribution and development in other nuclei of mouse visual thalamus. RESULTS: Immunolabeling specific subsets of synapses with antibodies against vesicle-associated neurotransmitter transporters or neurotransmitter synthesizing enzymes revealed significant differences in the composition, distribution and morphology of nonretinal terminals in dLGN, vLGN and IGL. For example, inhibitory terminals are more densely packed in vLGN, and cortical terminals are more densely distributed in dLGN. Overall, synaptic terminal density appears least dense in IGL. Similar nuclei-specific differences were observed for retinal terminals using immunolabeling, genetic labeling, axonal tracing and serial block face scanning electron microscopy: retinal terminals are smaller, less morphologically complex, and more densely distributed in vLGN than in dLGN. Since glutamatergic terminal size often correlates with synaptic function, we used in vitro whole cell recordings and optic tract stimulation in acutely prepared thalamic slices to reveal that excitatory postsynaptic currents (EPSCs) are considerably smaller in vLGN and show distinct responses following paired stimuli. Finally, anterograde labeling of retinal terminals throughout early postnatal development revealed that anatomical differences in retinal nerve terminal structure are not observable as synapses initially formed, but rather developed as retinogeniculate circuits mature. CONCLUSIONS: Taken together, these results reveal nuclei-specific differences in nerve terminal composition, distribution, and morphology in mouse visual thalamus. These results raise intriguing questions about the different functions of these nuclei in processing light-derived information, as well as differences in the mechanisms that underlie their unique, nuclei-specific development.

Lateral Geniculate Body Evoked Potentials Elicited by Visual and Electrical Stimulation

PURPOSE: Blind individuals who have photoreceptor loss are known to perceive phosphenes with electrical stimulation of their remaining retinal ganglion cells. We proposed that implantable lateral geniculate body (LGB) stimulus electrode arrays could be used to generate phosphene vision. We attempted to refine the basic reference of the electrical evoked potentials (EEPs) elicited by microelectrical stimulations of the optic nerve, optic tract and LGB of a domestic pig, and then compared it to visual evoked potentials (VEPs) elicited by short-flash stimuli. METHODS: For visual function measurement, VEPs in response to short-flash stimuli on the left eye of the domestic pig were assessed over the visual cortex at position Oz with the reference electrode at Fz. After anesthesia, linearly configured platinum wire electrodes were inserted into the optic nerve, optic track and LGB. To determine the optimal stimulus current, EEPs were recorded repeatedly with controlling the pulse and power. The threshold of current and charge density to elicit EEPs at 0.3 ms pulse duration was about ±10 microA. RESULTS: Our experimental results showed that visual cortex activity can be effectively evoked by stimulation of the optic nerve, optic tract and LGB using penetrating electrodes. The latency of P1 was more shortened as the electrical stimulation was closer to LGB. The EEPs of two-channel in the visual cortex demonstrated a similar pattern with stimulation of different spots of the stimulating electrodes. We found that the LGB-stimulated EEP pattern was very similar to the simultaneously generated VEP on the control side, although implicit time deferred. CONCLUSIONS: EEPs and VEPs derived from visual-system stimulation were compared. The LGB-stimulated EEP wave demonstrated a similar pattern to the VEP waveform except implicit time, indicating prosthetic-based electrical stimulation of the LGB could be utilized for the blind to perceive vision of phosphenes.