Hamada, E. | Search bioRxiv

bioRxiv2024

Inter- and Intrahemispheric Sources of Vestibular Signals to V1

Head movements are sensed by the vestibular organs. Unlike classical senses, signals from vestibular organs are not conveyed to a dedicated cortical area but are broadcast throughout the cortex. Surprisingly, the routes taken by vestibular signals to reach the cortex are still largely uncharted. Here we show that the primary visual cortex (V1) receives real-time head movement signals -- direction, velocity, and acceleration -- from the ipsilateral pulvinar and contralateral visual cortex. The ipsilateral pulvinar provides the main head movement signal, with a bias toward contraversive movements (e.g. clockwise movements in left V1). Conversely, the contralateral visual cortex provides head movement signals during ipsiversive movements. Crucially, head movement variables encoded in V1 are already encoded in the pulvinar, suggesting that those variables are computed subcortically. Thus, the convergence of inter- and intrahemispheric signals endows V1 with a rich representation of the animals head movements.

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bioRxiv2023

The functionally plastic rod photoreceptors in the simplex retina of Little skate (Leucoraja erinacea) exhibit a hybrid rod-cone morphology and enhanced synaptic connectivity.

The retinas of the vast majority of vertebrate species are termed "duplex" - that is, they contain both rod and cone photoreceptor neurons in different ratios. The retina of Little skate (Leucoraja erinacea) is a rarity among vertebrates because it contains only rod photoreceptors and is thus "simplex". This unique retina provides us with an important comparative model and an exciting opportunity to study vertebrate rod circuitry within the context of a functional, evolutionarily optimized system, all without the concern about artifacts from genetically modified rod-only mouse models. Perhaps even more importantly, the Leucoraja retina is able to function under both scotopic and photopic ranges of illumination with a single complement of photoreceptors. It is currently unknown what structural characteristics mediate this remarkable functional plasticity. To address this question, we performed serial block-face electron microscopy imaging and examined the structure of rods and their post-synaptic partners. We find that skate rods exhibit ultrastructural characteristics that are either common to rods or cones in other vertebrates (e.g., outer segment architecture, synaptic ribbon number, terminal extensions), or are uniquely in-between those of a typical vertebrate rod or cone (e.g., number of invaginating contacts, clustering of multiple ribbons over a single synaptic invagination). We therefore hypothesize that the unique hybrid rod-cone structure of skate rods and their post-synaptic partners is correlated with the ability of the skate visual system to function across scotopic and photopic ranges of illumination. These findings have the potential to reveal as yet undescribed principles of vertebrate retinal design. Significance statementThe vast majority of vertebrate retinas are duplex and have mixed rod-cone populations of photoreceptors in varying ratios. The processing of visual information in a duplex retina tends to be separated between rod and cone systems, which mediate function under scotopic and photopic lighting conditions, respectively. However, the cartilaginous fish Little skate (Leucoraja erinacea) has a simplex retina, comprised solely of rod photoreceptors. Skate rods are also unusual because they have the ability to retain function over a full range of lighting conditions. We have little knowledge about the ultrastructural anatomy of the skate retina, and we hypothesize that this functional plasticity can be traced back to morphological adaptations at the level of individual photoreceptors and the downstream retinal circuitry, thus illuminating new pathways for the processing of visual information among vertebrates.

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bioRxiv2023

Impaired cerebellar plasticity hypersensitizessensory reflexes in SCN2A-associated ASD

Children diagnosed with autism spectrum disorder (ASD) commonly present with sensory hypersensitivity, or abnormally strong reactions to sensory stimuli. Such hypersensitivity can be overwhelming, causing high levels of distress that contribute markedly to the negative aspects of the disorder. Here, we identify the mechanisms that underlie hypersensitivity in a sensorimotor reflex found to be altered in humans and in mice with loss-of-function in the ASD risk-factor gene SCN2A. The cerebellum-dependent vestibulo-ocular reflex (VOR), which helps maintain ones gaze during movement, was hypersensitized due to deficits in cerebellar synaptic plasticity. Heterozygous loss of SCN2A-encoded NaV1.2 sodium channels in granule cells impaired high-frequency transmission to Purkinje cells and long-term potentiation, a form of synaptic plasticity important for modulating VOR gain. VOR plasticity could be rescued in adolescent mice via a CRISPR-activator approach that increases Scn2a expression, highlighting how evaluation of simple reflexes can be used as quantitative readout of therapeutic interventions.

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