Dysfunction of the glutamatergic photoreceptor synapse in the P301S mouse model of tauopathy.

Tauopathies, including Alzheimer's disease, are characterized by retinal ganglion cell loss associated with amyloid and phosphorylated tau deposits. We investigated the functional impact of these histopathological alterations in the murine P301S model of tauopathy. Visual impairments were demonstrated by a decrease in visual acuity already detectable at 6 months, the onset of disease. Visual signals to the cortex and retina were delayed at 6 and 9 months, respectively. Surprisingly, the retinal output signal was delayed at the light onset and advanced at the light offset. This antagonistic effect, due to a dysfunction of the cone photoreceptor synapse, was associated with changes in the expression of the vesicular glutamate transporter and a microglial reaction. This dysfunction of retinal glutamatergic synapses suggests a novel interpretation for visual deficits in tauopathies and it highlights the potential value of the retina for the diagnostic assessment and the evaluation of therapies in Alzheimer's disease and other tauopathies.

Functional ultrasound imaging of the spreading activity following optogenetic stimulation of the rat visual cortex.

Optogenetics has revolutionized neurosciences by allowing fine control of neuronal activity. An important aspect for this control is assessing the activation and/or adjusting the stimulation, which requires imaging the entire volume of optogenetically-induced neuronal activity. An ideal technique for this aim is fUS imaging, which allows one to generate brain-wide activation maps with submesoscopic spatial resolution. However, optical stimulation of the brain with blue light might lead to non-specific activations at high irradiances. fUS imaging of optogenetic activations can be obtained at these wavelengths using lower light power (< 2mW) but it limits the depth of directly activatable neurons from the cortical surface. Our main goal was to report that we can detect specific optogenetic activations in V1 even in deep layers following stimulation at the cortical surface. Here, we show the possibility to detect deep optogenetic activations in anesthetized rats expressing the red-shifted opsin ChrimsonR in V1 using fUS imaging. We demonstrate the optogenetic specificity of these activations and their neuronal origin with electrophysiological recordings. Finally, we show that the optogenetic response initiated in V1 spreads to downstream (LGN) and upstream (V2) visual areas.

Analysis of the black-chinned tilapia Sarotherodon melanotheron heudelotii reproducing under a wide range of salinities: from RNA-seq to candidate genes.

The black-chinned tilapia Sarotherodon melanotheron heudelotii is an ecologically appealing model as it shows exceptional adaptive capacities, especially with regard to salinity. In spite of this, this species is devoid of genomic resources, which impedes the understanding of such remarkable features. De novo assembly of transcript sequences produced by next-generation sequencing technologies offers a rapid approach to obtain expressed gene sequences for non-model organisms. It also facilitates the development of quantitative real-time PCR (qPCR) assays for analysing gene expression under different environmental conditions. Nevertheless, obtaining accurate and reliable qPCR results from such data requires a number of validations prior to interpretation. The transcriptome of S. melanotheron was sequenced to discover transcripts potentially involved in the plasticity of male reproduction in response to salinity variations. A set of 54 candidate and reference genes was selected through a digital gene expression (DGE) approach, and a de novo qPCR assay using these genes was validated for further detailed expression analyses. A user-friendly web interface was created for easy handling of the sequence data. This sequence collection represents a major transcriptomic resource for S. melanotheron and will provide a useful tool for functional genomics and genetics studies.