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Guido, W.

Publications and source records attributed to Guido, W..

3 recordsLinked to original sources

A mouse model for cerebral/cortical visual impairment (CVI) impairs vision and disrupts the spatial frequency tuning of neurons in visual cortex

Cerebral/cortical visual impairment (CVI) is a visual disorder associated with perinatal hypoxic injury. The pathophysiology of CVI is poorly understood in part because of the lack of an animal model. Here we developed a murine model of CVI from existing rodent early postnatal hypoxia models for periventricular leukomalacia. Exposure to hypoxia during the equivalent to the human third trimester did not perturb motor function but caused severe impairments in binocular depth perception and visual acuity. Impaired vision was associated with normal retinal function, but reduced size of the visual thalamus, and aberrant tuning for spatial frequency by populations of excitatory neurons in primary visual cortex. This murine model of CVI provides a framework for triangulating circuit deficits with specific visual impairments and testing potential therapeutic interventions.

neuroscience↗

Cell-type specific binocular interactions in mouse visual thalamus

Projections from each eye are segregated in separate domains within the dorsal lateral geniculate nucleus (dLGN). Yet, in vivo studies indicate that the activity of single dLGN neurons can be influenced by visual stimuli presented to either eye. In this study we explored whether intrinsic circuits mediate binocular interactions in the mouse dLGN. We employed dual color optogenetics in vitro to selectively activate input from each eye and recorded synaptic responses in thalamocortical (relay) cells as well as inhibitory interneurons, which have extensive dendritic arbors that are not confined to eye specific domains. While most relay cells received monocular retinal input, most interneurons received binocular retinal input; consequently, the majority of dLGN relay cells received binocular retinogeniculate-evoked inhibition. Moreover, in recordings from adjacent pairs of relay cells and interneurons, the most common relationship observed was binocular excitation of interneurons paired with binocular inhibition of adjacent relay cells. Finally, we found that dLGN interneurons are interconnected, displaying both monocular and binocular inhibition in response to retinal activation. In sum, our results indicate that geniculate interneurons provide one of the first locations where signals from the two eyes can be compared, integrated, and adjusted before being transmitted to cortex, shedding new light on the role of the thalamus in binocular vision. HighlightsO_LIIn vitro dual color optogenetics examined convergence of eye-specific retinal inputs to thalamocortical (relay) cells and interneurons in the dLGN C_LIO_LIThe majority of relay cells receive monocular excitatory retinogeniculate input while the majority of interneurons receive binocular input C_LIO_LIBinocular relay cells are located in and around the ipsilateral patch whereas binocular interneurons are distributed throughout the dLGN C_LIO_LIThe majority of relay cells receive binocular retinogeniculate-evoked inhibition C_LIO_LIdLGN interneurons are interconnected, receiving both monocular and binocular retinogeniculate-evoked inhibition C_LI

neuroscience↗

Diverse GABAergic neurons organize into subtype-specific sublaminae in the ventral lateral geniculate nucleus

In the visual system, retinal axons convey visual information from the outside world to dozens of distinct retinorecipient brain regions and organize that information at several levels, including either at the level of retinal afferents, cytoarchitecture of intrinsic retinorecipient neurons, or a combination of the two. Two major retinorecipient nuclei which are densely innervated by retinal axons are the dorsal lateral geniculate nucleus (dLGN), which is important for classical image-forming vision, and ventral LGN (vLGN), which is associated with non-image-forming vision. The neurochemistry, cytoarchitecture, and retinothalamic connectivity in vLGN remain unresolved, raising fundamental questions of how it receives and processes visual information. To shed light on these important questions, we labeled neurons in vLGN with canonical and novel cell type-specific markers and studied their spatial distribution and morphoelectric properties. Not only did we find a high percentage of cells in vLGN to be GABAergic, we discovered transcriptomically distinct GABAergic cell types reside in the two major laminae of vLGN, the retinorecipient, external vLGN (vLGNe) and the non-retinorecipient, internal vLGN (vLGNi). Within vLGNe, we identified transcriptionally distinct subtypes of GABAergic cells that are distributed into four adjacent sublaminae. Using trans-synaptic viral tracing and in vitro electrophysiology, we found cells in each these vLGNe sublaminae receive monosynaptic inputs from the retina. These results not only identify novel subtypes of GABAergic cells in vLGN, they suggest the subtype-specific laminar distribution of retinorecipient cells in vLGNe may be important for receiving, processing, and transmitting light-derived signals in parallel channels of the subcortical visual system. Graphical abstract. The vLGN is organized into subtype-specific sublaminae which receive visual inputThe ventral lateral geniculate nucleus (vLGN) is part of the visual thalamus. It can broadly be separated into two structural domains or laminae, the external vLGNe (which receives retinal input) and the internal vLGNi (receives no retinal input). In this study, we describe subtypes of transcriptomically distinct GABAergic neurons that populate the vLGN and organize into discrete, adjacent sublaminae in the vLGNe. Taken together, our results show four subtype-specific sublaminae of retinorecipient neurons in vLGNe. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=87 SRC="FIGDIR/small/073197v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@1739b12org.highwire.dtl.DTLVardef@c9e9a6org.highwire.dtl.DTLVardef@a92b8org.highwire.dtl.DTLVardef@267956_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗