Efficient coding of natural scenes improves neural system identification.

Neural system identification aims at learning the response function of neurons to arbitrary stimuli using experimentally recorded data, but typically does not leverage normative principles such as efficient coding of natural environments. Visual systems, however, have evolved to efficiently process input from the natural environment. Here, we present a normative network regularization for system identification models by incorporating, as a regularizer, the efficient coding hypothesis, which states that neural response properties of sensory representations are strongly shaped by the need to preserve most of the stimulus information with limited resources. Using this approach, we explored if a system identification model can be improved by sharing its convolutional filters with those of an autoencoder which aims to efficiently encode natural stimuli. To this end, we built a hybrid model to predict the responses of retinal neurons to noise stimuli. This approach did not only yield a higher performance than the "stand-alone" system identification model, it also produced more biologically plausible filters, meaning that they more closely resembled neural representation in early visual systems. We found these results applied to retinal responses to different artificial stimuli and across model architectures. Moreover, our normatively regularized model performed particularly well in predicting responses of direction-of-motion sensitive retinal neurons. The benefit of natural scene statistics became marginal, however, for predicting the responses to natural movies. In summary, our results indicate that efficiently encoding environmental inputs can improve system identification models, at least for noise stimuli, and point to the benefit of probing the visual system with naturalistic stimuli.

Natural environment statistics in the upper and lower visual field are reflected in mouse retinal specializations.

Pressures for survival make sensory circuits adapted to a species' natural habitat and its behavioral challenges. Thus, to advance our understanding of the visual system, it is essential to consider an animal's specific visual environment by capturing natural scenes, characterizing their statistical regularities, and using them to probe visual computations. Mice, a prominent visual system model, have salient visual specializations, being dichromatic with enhanced sensitivity to green and UV in the dorsal and ventral retina, respectively. However, the characteristics of their visual environment that likely have driven these adaptations are rarely considered. Here, we built a UV-green-sensitive camera to record footage from mouse habitats. This footage is publicly available as a resource for mouse vision research. We found chromatic contrast to greatly diverge in the upper, but not the lower, visual field. Moreover, training a convolutional autoencoder on upper, but not lower, visual field scenes was sufficient for the emergence of color-opponent filters, suggesting that this environmental difference might have driven superior chromatic opponency in the ventral mouse retina, supporting color discrimination in the upper visual field. Furthermore, the upper visual field was biased toward dark UV contrasts, paralleled by more light-offset-sensitive ganglion cells in the ventral retina. Finally, footage recorded at twilight suggests that UV promotes aerial predator detection. Our findings support that natural scene statistics shaped early visual processing in evolution.

Correction to: Overexpression of CAV3 facilitates bone formation via the Wnt signaling pathway in osteoporotic rats.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Retinal Circuits for Seeing in the Dark.

How can we relate processing in the retina to an animal's behavior? In this issue of Neuron, Smeds et al. (2019) report that when "every photon counts," mice trade sensitivity for reliability to master visual tasks.

An arbitrary-spectrum spatial visual stimulator for vision research.

Visual neuroscientists require accurate control of visual stimulation. However, few stimulator solutions simultaneously offer high spatio-temporal resolution and free control over the spectra of the light sources, because they rely on off-the-shelf technology developed for human trichromatic vision. Importantly, consumer displays fail to drive UV-shifted short wavelength-sensitive photoreceptors, which strongly contribute to visual behaviour in many animals, including mice, zebrafish and fruit flies. Moreover, many non-mammalian species feature more than three spectral photoreceptor types. Here, we present a flexible, spatial visual stimulator with up to six arbitrary spectrum chromatic channels. It combines a standard digital light processing engine with open source hard- and software that can be easily adapted to the experimentalist's needs. We demonstrate the capability of this general visual stimulator experimentally in the in vitro mouse retinal whole-mount and the in vivo zebrafish. With this work, we intend to start a community effort of sharing and developing a common stimulator design for vision research.

MiRNA-19a-3p alleviates the progression of osteoporosis by targeting HDAC4 to promote the osteogenic differentiation of hMSCs.

To clarify the function of microRNA-19a-3p (miRNA-19a-3p) in the osteogenic differentiation of human-derived mesenchymal stem cells (hMSCs) and the potential mechanism. Serum levels of miRNA-19a-3p, RUNX2 and OCN in osteoporosis patients and controls were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Alkaline phosphatase (ALP) content and calcification ability during the process of osteogenic differentiation were examined by ALP staining and alizarin red staining, respectively. After altering miRNA-19a-3p level by transfection of miRNA-19a-3p mimic or inhibitor, we detected relative levels of miRNA-19a-3p, RUNX2 and OCN in hMSCs by qRT-PCR. The binding relationship between miRNA-19a-3p and HDAC4 was predicted by TargetScan and further verified by dual-luciferase reporter gene assay. Relative expression of HDAC4 was detected by Western blot and qRT-PCR in hMSCs transfected with miRNA-19a-3p mimic or inhibitor. Regulatory effects of miRNA-19a-3p/HDAC4 axis on osteogenic differentiation of hMSCs were evaluated. MiRNA-19a-3p was downregulated in osteoporosis patients. Its level gradually increased in hMSCs with the prolongation of osteogenic differentiation. Overexpression of miRNA-19a-3p upregulated levels of RUNX2 and OCN, and enhanced ALP activity. Knockdown of miRNA-19a-3p obtained the opposite trends. Dual-luciferase reporter gene assay verified that miRNA-19a-3p could target to 3'UTR of HDAC4. Protein level of HDAC4 was negatively regulated by miRNA-19a-3p in hMSCs. More importantly, co-overexpression of miRNA-19a-3p and HDAC4 could reverse the regulatory effects of miRNA-19a-3p on enhancing ALP activity and upregulating RUNX2 and OCN. MiRNA-19a-3p promotes the osteogenic differentiation of hMSCs by inhibiting HDAC4 expression, thus alleviating the progression of osteoporosis.

Overexpression of CAV3 facilitates bone formation via the Wnt signaling pathway in osteoporotic rats.

PURPOSE: Osteoporosis is a condition characterized by decreased bone density and bone strength, commonly observed among older individuals. Caveolin-3 (CAV3) is a principal structural protein of the caveolae membrane domains, which has been reported to participate in cell signaling as well as the maintenance of cell structure. The aim of the current study was to investigate the effects involved with the silencing of CAV3 on bone formation among osteoporotic rat models via the Wnt signaling pathway. METHODS: Osteoporosis was initially induced by means of ovariotomy among rat models in order to determine the expression of CAV3. Then, to confirm the specific function and mechanism of CAV3 from an osteoporosis perspective, the CAV3 expression vector was constructed and transfected into the osteoblasts of the osteoporotic rats. Afterward, the mRNA and protein expressions of CAV3, ß-catenin, low-density lipoprotein receptor-related protein 5 (LRP5), T-cell factor (TCF), and Wnt3a in addition to cell proliferation and apoptosis were detected accordingly. RESULTS: Positive expression of CAV3 exhibited diminished levels in the bone tissues of osteoporotic rats. The osteoblasts of the osteoporotic rats treated with overexpressed CAV3 displayed elevated mRNA and protein expression levels of ß-catenin, LRP5, TCF, and Wnt3a. Increased cell proliferation and decreased cell apoptosis were also observed, while the osteoblasts of the osteoporotic rats treated with si-CAV3 exhibited an opposite result. CONCLUSION: Overexpressed CAV3 promotes bone formation and suppresses the osteoporosis progression via the activation of the Wnt signaling in rat models, suggesting CAV3 as a potential target biomarker in the treatment of osteoporosis.