Differential Expression of DSCAM Guides the Patterning of Retinal Axons Along Their Path and at Their Target in the Developing Xenopus Visual System

Background The Xenopus retinotectal circuit is organized topographically, where the dorsal-ventral axis of the retina maps respectively on to the ventral-dorsal axis of the tectum; axons from the nasal-temporal axis of the retina project respectively to the caudal-rostral axis of the tectum. Studies throughout the last two decades have shown that mechanisms involving molecular recognition of proper termination domains are at work guiding topographic organization. Such studies have shown that graded distribution of molecular cues is important for topographic mapping. However, the molecular cues organizing topography along the developing optic nerve, and as retinal axons cross the chiasm and navigate towards their target in the tectum, remain unknown. Down syndrome cell adhesion molecule (DSCAM) has been characterized as a key molecule in axon guidance, making it a strong candidate involved in the topographic organization of retinal fibers along the optic path.Methods Using a combination of whole-brain clearing and immunohistochemistry staining techniques we characterized DSCAM expression and the projection of ventral and dorsal retinal fibers starting from the eye, followed to the optic nerve into the chiasm, and into the terminal target in the optic tectum in Xenopus laevis tadpoles. We also assessed the effects of DSCAM on the establishment of retinotopic maps through spatially and temporally targeted DSCAM knockdown on retinal ganglion cells (RGCs) with axons innervating the optic tectum. Results Highest expression of DSCAM was localized to the ventral posterior region of the optic nerve and chiasm; this expression pattern coincides with ventral fibers derived from ventral RGCs. Downregulating DSCAM levels affected the segregation and proper sorting of medial axon fibers, derived from ventral RGCs, within the tectal neuropil, indicating that DSCAM plays a role in retinotopic organization. ConclusionThese findings together with the observation that DSCAM immunoreactivity accumulates on the primary dendrites of tectal neurons indicates that DSCAM exerts multiple roles in coordinating retinotopic order and connectivity in the developing vertebrate visual system.

Highly accurate retinotopic maps of the physiological blind spot in human visual cortex

The physiological blind spot is a naturally occurring scotoma corresponding with the optic disc in the retina of each eye. Even during monocular viewing, observers are usually oblivious to the scotoma, in part because the visual system extrapolates information from the surrounding area. Unfortunately, studying this visual field region with neuroimaging has proven difficult, as it occupies only a small part of retinotopic cortex. Here we used functional magnetic resonance imaging and a novel data-driven method for mapping the retinotopic organization in and around the blind spot representation in V1. Our approach allowed for highly accurate reconstructions of the extent of an observer's blind spot, and out-performed conventional model-based analyses. This method opens exciting opportunities to study the plasticity of receptive fields after visual field loss, and our data add to evidence suggesting that the neural circuitry responsible for impressions of perceptual completion across the physiological blind spot most likely involves regions of extrastriate cortex - beyond V1.

Non‐invasive real‐time access to spatial attention information from 3T fMRI BOLD signals

Access to higher cognitive functions in real-time remains very challenging, because these functions are internally driven and their assessment is based onto indirect measures. In addition, recent finding show that these functions are highly dynamic. Previous studies using intra-cortical recordings in monkeys, succeed to access the (x,y) position of covert spatial attention, in real-time, using classification methods applied to monkey prefrontal multi-unit activity and local field potentials. In contrast, the direct access to attention with non-invasive methods is limited to predicting the attention localisation based on a quadrant classification. Here, we demonstrate the feasibility to track covert spatial attention localization using non-invasive fMRI BOLD signals, with an unprecedented spatial resolution. We further show that the errors produced by the decoder are not randomly distributed but concentrate on the locations neighbouring the cued location and that behavioral errors correlate with weaker decoding performance. Last, we also show that the voxels contributing to the decoder precisely match the visual retinotopic organization of the occipital cortex and that single trial access to attention is limited by the intrinsic dynamics of spatial attention. Taken together, these results open the way to the development of remediation and enhancement neurofeedback protocols targeting the attentional function.

Population receptive fields in non-human primates from whole-brain fMRI and large-scale neurophysiology in visual cortex in visual cortex

Population receptive field (pRF) modeling is a popular fMRI method to map the retinotopic organization of the human brain. While fMRI-based pRF-maps are qualitatively similar to invasively recorded single-cell receptive fields in animals, it remains unclear what neuronal signal they represent. We addressed this question in awake non-human primates comparing whole-brain fMRI and large-scale neurophysiological recordings in areas V1 and V4 of the visual cortex. We examined the fits of several pRF-models based on the fMRI BOLD-signal, multi-unit spiking activity (MUA) and local field potential (LFP) power in different frequency bands. We found that pRFs derived from BOLD-fMRI were most similar to MUA-pRFs in V1 and V4, while pRFs based on LFP gamma power also gave a good approximation. FMRI-based pRFs thus reliably reflect neuronal receptive field properties in the primate brain. In addition to our results in V1 and V4, the whole-brain fMRI measurements revealed retinotopic tuning in many other cortical and subcortical areas with a consistent increase in pRF-size with increasing eccentricity, as well as a retinotopically specific deactivation of default-mode network nodes similar to previous observations in humans.

BOLD fMRI signals of visual white matter encode visuotopic information and predict effective connectivity between visual areas

The functional significance of BOLD signals in white matter (WM) remains unclear. The current study investigated whether 7T BOLD fMRI signal from visual WM tracts contains high fidelity retinotopic information and whether it correlates with the effective connectivity between visual areas. Population receptive field (pRF) analysis of the 7T retinotopy dataset from the Human Connectome Project revealed clear contralateral retinotopic representations from two visual WM bundles: optic radiation (OR) and vertical occipital fasciculus (VOF). The retinotopic organization of OR is consistent with post-mortem studies. The pRF size of WM voxels also increases with eccentricity. Based on the retinotopic maps of OR, we investigated whether BOLD signals in OR during visual stimulation are related to the resting-state effective connectivity between the lateral geniculate nucleus (LGN) and the primary visual cortex (V1). Results show that visually-evoked BOLD responses in OR correlate with the feedforward and feedback connectivity between the LGN and V1 during resting state. These findings demonstrate that WM BOLD signals contain high fidelity information such as visual field maps, and also predict the functional connectivity of brain areas.

Brain areas associated with visual spatial attention display topographic organization during auditory spatial attention

It is well-established that power modulations of alpha oscillations (8-14 Hz) reflect the retinotopic organization of visuospatial attention. To what extend this organization generalizes to other sensory modalities is a topic of ongoing scientific debate. Here, we designed an auditory paradigm eliminating any visual input in which participants were required to attend to upcoming sounds from one of 24 loudspeakers arranged in a horizontal circular array around the head. Maintaining the location of an auditory cue was associated with a topographically modulated distribution of posterior alpha power resembling the findings known from visual attention. Alpha power modulations in all electrodes allowed us to predict the sound location in the horizontal plane using a forward encoding model. Importantly, this prediction was still possible, albeit weaker, when derived from the horizontal electrooculogram capturing saccadic behavior. We conclude that attending to an auditory target engages oculomotor and visual cortical areas in a topographic manner akin to the retinotopic organization associated with visual attention suggesting that the spatial distribution of alpha power reflects the supramodal organization of egocentric space.