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In-sensor and near-sensor computing architectures enable multiply accumulate operations to be carried out directly at the point of sensing. In-sensor architectures offer dramatic power and speed improvements over traditional von Neumann architectures by eliminating multiple analog-to-digital conversions, data storage, and data movement operations. Current in-sensor processing approaches rely on tunable sensors or additional weighting elements to perform linear functions such as multiply accumulate operations as the sensor acquires data. This work implements in-sensor computing with an oscillatory retinal neuron device that converts incident optical signals into voltage oscillations. A computing scheme is introduced based on the frequency shift of coupled oscillators that enables parallel, frequency multiplexed, nonlinear operations on the inputs. An experimentally implemented 3 × 3 focal plane array of coupled neurons shows that functions approximating edge detection, thresholding, and segmentation occur in parallel . An example of inference on handwritten digits from the MNIST database is also experimentally demonstrated with a 3 × 3 array of coupled neurons feeding into a single hidden layer neural network, approximating a liquid-state machine. Finally, the equivalent energy consumption to carry out image processing operations, including peripherals such as the Fourier transform circuits, is projected to be <20 fJ/OP, possibly reaching as low as 15 aJ/OP.

To realize a low-cost neuromorphic visual system, employing an artificial neuron capable of mimicking the retinal neuron functions is essential. A photoresponsive single transistor neuron composed of a vertical silicon nanowire is proposed. Similar to retinal neurons, various photoresponsive characteristics of the single transistor neuron can be modulated by light intensity as well as wavelength and have a high responsivity to green light like the human eye. The device is designed with a cylindrical surrounding double-gate structure, enclosed by an independently controlled outer gate and inner gate. The outer gate has the function of selectively inhibiting neuron activity, which can mimic lateral inhibition of amacrine cells to ganglion cells, and the inner gate can be utilized for the adjustment of the firing threshold voltage, which can be used to mimic the regulation of photoresponsivity by horizontal cells for adaptive visual perception. Furthermore, a myelination function that controls the speed of information transmission is obtained according to the inherent asymmetric source/drain structure of a vertical silicon nanowire. This work can enable photoresponsive neuronal function using only a single transistor, providing a promising hardware implementation for building miniaturized neuromorphic vision systems at low cost., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the interrelationship among the outer retinal layers after macular hole surgery and elucidate the restoration process., Methods: This retrospective observational study included 50 eyes of 47 consecutive patients with closed macular holes in the first vitrectomy. Optical coherence tomography was obtained before surgery; at 1, 3, and 6 months postsurgery; and at the last visit. The complete continuous layer rate and mean defect length were evaluated for the outer nuclear layer (ONL), external limiting membrane (ELM), and ellipsoid zone (EZ)., Results: At all postoperative visits, the complete continuous layer rate was in the descending order of ELM, ONL, and EZ and the mean defect length was in the ascending order of ELM, ONL, and EZ. External limiting membrane was necessary for ONL restoration. External limiting membrane and ONL were necessary for EZ restoration. Hyperreflective protrusions were observed from the area lacking ELM into the subretinal space after surgery. Ellipsoid zone was not formed in coexistence with the hyperreflective protrusions. Intermediate reflective protrusions appeared under the ONL plus ELM after surgery and were eventually replaced by EZ., Conclusion: Restoration of the outer retinal layers after surgical macular hole closure occurs in the order of ELM, ONL, and EZ.

Purpose: Luminance contrast is the fundamental building block of human spatial vision. Therefore contrast sensitivity, the reciprocal of contrast threshold required for target detection, has been a barometer of human visual function. Although retinal ganglion cells (RGCs) are known to be involved in contrast coding, it still remains unknown whether the retinal layers containing RGCs are linked to a person's contrast sensitivity (e.g., Pelli-Robson contrast sensitivity) and, if so, to what extent the retinal layers are related to behavioral contrast sensitivity. Thus the current study aims to identify the retinal layers and features critical for predicting a person's contrast sensitivity via deep learning., Methods: Data were collected from 225 subjects including individuals with either glaucoma, age-related macular degeneration, or normal vision. A deep convolutional neural network trained to predict a person's Pelli-Robson contrast sensitivity from structural retinal images measured with optical coherence tomography was used. Then, activation maps that represent the critical features learned by the network for the output prediction were computed., Results: The thickness of both ganglion cell and inner plexiform layers, reflecting RGC counts, were found to be significantly correlated with contrast sensitivity (r = 0.26 ∼ 0.58, Ps < 0.001 for different eccentricities). Importantly, the results showed that retinal layers containing RGCs were the critical features the network uses to predict a person's contrast sensitivity (an average R2 = 0.36 ± 0.10)., Conclusions: The findings confirmed the structure and function relationship for contrast sensitivity while highlighting the role of RGC density for human contrast sensitivity.

Brain plasticity is a well-established concept designating the ability of central nervous system (CNS) neurons to rearrange as a result of learning, when adapting to changeable environmental conditions or else while reacting to injurious factors. As a part of the CNS, the retina has been repeatedly probed for its possible ability to respond plastically to a variably altered environment or to pathological insults. However, numerous studies support the conclusion that the retina, outside the developmental stage, is endowed with only limited plasticity, exhibiting, instead, a remarkable ability to maintain a stable architectural and functional organization. Reviewed here are representative examples of hippocampal and cortical paradigms of plasticity and of retinal structural rearrangements found in organization and circuitry following altered developmental conditions or occurrence of genetic diseases leading to neuronal degeneration. The variable rate of plastic changes found in mammalian retinal neurons in different circumstances is discussed, focusing on structural plasticity. The likely adaptive value of maintaining a low level of plasticity in an organ subserving a sensory modality that is dominant for the human species and that requires elevated fidelity is discussed.

Purpose: After the lateral geniculate nucleus, the superior colliculus is the richest target of retinal projections in primates. Hubel et al. used tritium autoradiography to show that axon terminals emanating from one eye form irregular columns in the stratum griseum superficiale. Unlabeled gaps were thought to be filled by the other eye, but this assumption was never tested directly., Methods: Experiments were performed in two normal macaques. In monkey 1, [3H]proline was injected into the left eye and the pattern of radiolabeling was examined in serial cross-sections through the entire superior colliculus. In monkey 2, cholera toxin subunit B conjugated to Alexa 488 was injected into the right eye and cholera toxin subunit B - Alexa 594 was injected into the left eye. The two fluorescent labels were compared in a reconstruction of the superior colliculus prepared from serial sections., Results: In monkey 1, irregular columns of axon terminals were present in the superficial grey. The projection from the peripheral retina was stronger than the projection from the macula. In monkey 2, the two fluorescent Alexa tracers mainly interdigitated: a conspicuous gap in one label was usually filled by a clump of the other label. There was also partial laminar segregation of ocular inputs. In the far peripheral field representation, the contralateral eye's input generally terminated closer to the tectal surface. In the midperiphery the eyes switched, bringing the ipsilateral input nearer the surface., Conclusions: Direct retinal input to the macaque superior colliculus is segregated into alternating columns and strata, despite the fact that tectal cells respond robustly to stimulation of either eye.

The adult mammal lacks the ability to regenerate neurons lost to retinal damage or disease in a meaningful capacity. However, previous studies from this laboratory have demonstrated that PNU-282987, an α7 nicotinic acetylcholine receptor agonist, elicits a robust neurogenic response in the adult murine retina. With eye drop application of PNU-282987, Müller glia cells re-enter the cell cycle and produce progenitor-like cells that can differentiate into various types of retinal neurons. In this study, we analyzed the regenerative capability of PNU-282987 in two retinal disease models and identified the source of newly regenerated neurons. Wild-type mice and mice with a transgenic Müller-glia lineage tracer were manipulated to mimic loss of retinal cells associated with glaucoma or photoreceptor degeneration. Following treatment with PNU-282987, the regenerative response of retinal neurons was quantified and characterized. After onset of photoreceptor degeneration, PNU-282987 was able to successfully regenerate both rod and cone photoreceptors. Quantification of this response demonstrated significant regeneration, restoring photoreceptors to near wild-type density. In mice that had glaucoma-like conditions induced, PNU-282987 treatment led to a significant increase in retinal ganglion cells. Retrograde labeling of optic nerve axon fibers demonstrated that newly regenerated axons projected into the optic nerve. Lineage tracing analysis demonstrated that these new neurons were derived from Müller glia. These results demonstrate that PNU-282987 can induce retinal regeneration in adult mice following onset of retinal damage. The ability of PNU-282987 to regenerate retinal neurons in a robust manner offers a new direction for developing novel and potentially transformative treatments to combat neurodegenerative disease., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

(1) Background: High-tension glaucoma damages the peripheral vision dominated by rods. How mechanosensitive channels (MSCs) in the outer retina mediate pressure responses is unclear. (2) Methods: Immunocytochemistry, patch clamp, and channel fluorescence were used to study MSCs in salamander photoreceptors. (3) Results: Immunoreactivity of transient receptor potential channel vanilloid 4 (TRPV4) was revealed in the outer plexiform layer, K + channel TRAAK in the photoreceptor outer segment (OS), and TRPV2 in some rod OS disks. Pressure on the rod inner segment evoked sustained currents of three components: (A) the inward current at <-50 mV ( I pi ), sensitive to Co 2+ ; (B) leak outward current at ≥-80 mV ( I po ), sensitive to intracellular Cs + and ruthenium red; and (C) cation current reversed at ~10 mV ( I pc ). Hypotonicity induced slow currents like I pc . Environmental pressure and light increased the FM 1-43-identified open MSCs in the OS membrane, while pressure on the OS with internal Cs + closed a Ca 2+ -dependent current reversed at ~0 mV. Rod photocurrents were thermosensitive and affected by MSC blockers. (4) Conclusions: Rods possess depolarizing (TRPV) and hyperpolarizing (K + ) MSCs, which mediate mutually compensating currents between -50 mV and 10 mV, serve as an electrical cushion to minimize the impact of ocular mechanical stress.

Output signals of neural circuits, including the retina, are shaped by a combination of excitatory and inhibitory signals. Inhibitory signals can act presynaptically on axon terminals to control neurotransmitter release and regulate circuit function. However, it has been difficult to study the role of presynaptic inhibition in most neural circuits due to lack of cell type-specific and receptor type-specific perturbations. In this study, we used a transgenic approach to selectively eliminate GABA A inhibitory receptors from select types of second-order neurons - bipolar cells - in mouse retina and examined how this affects the light response properties of the well-characterized ON alpha ganglion cell retinal circuit. Selective loss of GABA A receptor-mediated presynaptic inhibition causes an enhanced sensitivity and slower kinetics of light-evoked responses from ON alpha ganglion cells thus highlighting the role of presynaptic inhibition in gain control and temporal filtering of sensory signals in a key neural circuit in the mammalian retina., Competing Interests: JN, BE, MH, RS No competing interests declared, (© 2021, Nagy et al.)

Regenerative medicine in ophthalmology that uses induced pluripotent stem cells (iPS) cells has been described, but those studies used iPS cells derived from fibroblasts. Here, we generated iPS cells derived from iris cells that develop from the same inner layer of the optic cup as the retina, to regenerate retinal nerves. We first identified cells positive for p75NTR, a marker of retinal tissue stem and progenitor cells, in human iris tissue. We then reprogrammed the cultured p75NTR-positive iris tissue stem/progenitor (H-iris stem/progenitor) cells to create iris-derived iPS (H-iris iPS) cells for the first time. These cells were positive for iPS cell markers and showed pluripotency to differentiate into three germ layers. When H-iris iPS cells were pre-differentiated into neural stem/progenitor cells, not all cells became positive for neural stem/progenitor and nerve cell markers. When these cells were pre-differentiated into neural stem/progenitor cells, sorted with p75NTR, and used as a medium for differentiating into retinal nerve cells, the cells differentiated into Recoverin-positive cells with electrophysiological functions. In a different medium, H-iris iPS cells differentiated into retinal ganglion cell marker-positive cells with electrophysiological functions. This is the first demonstration of H-iris iPS cells differentiating into retinal neurons that function physiologically as neurons.

Objective. To restore central vision in patients with atrophic age-related macular degeneration, we replace the lost photoreceptors with photovoltaic pixels, which convert light into current and stimulate the secondary retinal neurons. Clinical trials demonstrated prosthetic acuity closely matching the sampling limit of the 100 μ m pixels, and hence smaller pixels are required for improving visual acuity. However, with smaller flat bipolar pixels, the electric field penetration depth and the photodiode responsivity significantly decrease, making the device inefficient. Smaller pixels may be enabled by (a) increasing the diode responsivity using vertical p-n junctions and (b) directing the electric field in tissue vertically. Here, we demonstrate such novel photodiodes and test the retinal stimulation in a vertical electric field. Approach. Arrays of silicon photodiodes of 55, 40, 30, and 20 μ m in width, with vertical p-n junctions, were fabricated. The electric field in the retina was directed vertically using a common return electrode at the edge of the device. Optical and electronic performance of the diodes was characterized in-vitro , and retinal stimulation threshold measured by recording the visually evoked potentials in rats with retinal degeneration. Main results. The photodiodes exhibited sufficiently low dark current (<10 pA) and responsivity at 880 nm wavelength as high as 0.51 A W -1 , with 85% internal quantum efficiency, independent of pixel size. Field mapping in saline demonstrated uniformity of the pixel performance in the array. The full-field stimulation threshold was as low as 0.057±0.029mW mm -2 with 10 ms pulses, independent of pixel size. Significance. Photodiodes with vertical p-n junctions demonstrated excellent charge collection efficiency independent of pixel size, down to 20 μ m. Vertically oriented electric field provides a stimulation threshold that is independent of pixel size. These results are the first steps in validation of scaling down the photovoltaic pixels for subretinal stimulation., (© 2021 IOP Publishing Ltd.)

In this study, we report the results of a comprehensive phenotyping of the retina of the App NL-G-F mouse. We demonstrate that soluble Aβ accumulation is present in the retina of these mice early in life and progresses to Aβ plaque formation by midlife. This rising Aβ burden coincides with local microglia reactivity, astrogliosis, and abnormalities in retinal vein morphology. Electrophysiological recordings revealed signs of neuronal dysfunction yet no overt neurodegeneration was observed and visual performance outcomes were unaffected in the App NL-G-F mouse. Furthermore, we show that hyperspectral imaging can be used to quantify retinal Aβ, underscoring its potential as a biomarker for AD diagnosis and monitoring. These findings suggest that the App NL-G-F retina mimics the early, preclinical stages of AD, and, together with retinal imaging techniques, offers unique opportunities for drug discovery and fundamental research into preclinical AD.

Visual perception requires both visual information and attention. This review compares, across classes of vertebrates, the functional and anatomical characteristics of (a) the neural pathways that process visual information about objects, and (b) stimulus selection pathways that determine the objects to which an animal attends. Early in the evolution of vertebrate species, visual perception was dominated by information transmitted via the midbrain (retinotectal) visual pathway, and attention was probably controlled primarily by a selection network in the midbrain. In contrast, in primates, visual perception is dominated by information transmitted via the forebrain (retinogeniculate) visual pathway, and attention is mediated largely by networks in the forebrain. In birds and nonprimate mammals, both the retinotectal and retinogeniculate pathways contribute critically to visual information processing, and both midbrain and forebrain networks play important roles in controlling attention. The computations and processing strategies in birds and mammals share some strikingly similar characteristics despite over 300 million years of independent evolution and being implemented by distinct brain architectures. The similarity of these functional characteristics suggests that they provide valuable advantages to visual perception in advanced visual systems. A schema is proposed that describes the evolution of the pathways and computations that enable visual perception in vertebrate species., (© 2020 The Author. The Journal of Comparative Neurology published by Wiley Periodicals, Inc.)

During brain development, progenitor cells need to balanceproliferation and differentiation in order to generate different neurons in the correct numbers and proportions. Currently, the patterns of multipotent progenitor divisions that lead to neurogenic entry and the factors that regulate them are not fully understood. We here use the zebrafish retina to address this gap, exploiting its suitability for quantitative live-imaging. We show that early neurogenic progenitors arise from asymmetric divisions. Notch regulates this asymmetry, as when inhibited, symmetric divisions producing two neurogenic progenitors occur. Surprisingly however, Notch does not act through an apicobasal activity gradient as previously suggested, but through asymmetric inheritance of Sara-positive endosomes. Further, the resulting neurogenic progenitors show cell biological features different from multipotent progenitors, raising the possibility that an intermediate progenitor state exists in the retina. Our study thus reveals new insights into the regulation of proliferative and differentiative events during central nervous system development., Competing Interests: EN, MR, CN No competing interests declared, (© 2020, Nerli et al.)

The responses of visual neurons, as well as visual perception phenomena in general, are highly nonlinear functions of the visual input, while most vision models are grounded on the notion of a linear receptive field (RF). The linear RF has a number of inherent problems: it changes with the input, it presupposes a set of basis functions for the visual system, and it conflicts with recent studies on dendritic computations. Here we propose to model the RF in a nonlinear manner, introducing the intrinsically nonlinear receptive field (INRF). Apart from being more physiologically plausible and embodying the efficient representation principle, the INRF has a key property of wide-ranging implications: for several vision science phenomena where a linear RF must vary with the input in order to predict responses, the INRF can remain constant under different stimuli. We also prove that Artificial Neural Networks with INRF modules instead of linear filters have a remarkably improved performance and better emulate basic human perception. Our results suggest a change of paradigm for vision science as well as for artificial intelligence.

In humans, various genetic defects or age-related diseases, such as diabetic retinopathies, glaucoma, and macular degeneration, cause the death of retinal neurons and profound vision loss. One approach to treating these diseases is to utilize stem and progenitor cells to replace neurons in situ, with the expectation that new neurons will create new synaptic circuits or integrate into existing ones. Reprogramming non-neuronal cells in vivo into stem or progenitor cells is one strategy for replacing lost neurons. Zebrafish have become a valuable model for investigating cellular reprogramming and retinal regeneration. This review summarizes our current knowledge regarding spontaneous reprogramming of Müller glia in zebrafish and compares this knowledge to research efforts directed toward reprogramming Müller glia in mammals. Intensive research using these animal models has revealed shared molecular mechanisms that make Müller glia attractive targets for cellular reprogramming and highlighted the potential for curing degenerative retinal diseases from intrinsic cellular sources.

How astounding neuronal diversity arises from variable cell lineages in vertebrates remains mostly elusive. By in vivo lineage tracing of ∼1,000 single zebrafish retinal progenitors, we identified a repertoire of subtype-specific stereotyped neurogenic lineages. Remarkably, within these stereotyped lineages, GABAergic amacrine cells were born with photoreceptor cells, whereas glycinergic amacrine cells were born with OFF bipolar cells. More interestingly, post-mitotic differentiation blockage of GABAergic and glycinergic amacrine cells resulted in their respecification into photoreceptor and bipolar cells, respectively, suggesting lineage constraint in cell subtype specification. Using single-cell RNA-seq and ATAC-seq analyses, we further identified lineage-specific progenitors, each defined by specific transcription factors that exhibited characteristic chromatin accessibility dynamics. Finally, single pro-neural factors could specify different neuron types/subtypes in a lineage-dependent manner. Our findings reveal the importance of lineage context in defining neuronal subtypes and provide a demonstration of in vivo lineage-dependent induction of unique retinal neuron subtypes for treatment purposes., (© 2020 Wang et al.)

Diabetic retinopathy (DR) is a frequent complication of diabetes mellitus and an increasingly common cause of visual impairment. Blood vessel damage occurs as the disease progresses, leading to ischemia, neovascularization, blood-retina barrier (BRB) failure and eventual blindness. Although detection and treatment strategies have improved considerably over the past years, there is room for a better understanding of the pathophysiology of the diabetic retina. Indeed, it has been increasingly realized that DR is in fact a disease of the retina's neurovascular unit (NVU), the multi-cellular framework underlying functional hyperemia, coupling neuronal computations to blood flow. The accumulating evidence reveals that both neurochemical (synapses) and electrical (gap junctions) means of communications between retinal cells are affected at the onset of hyperglycemia, warranting a global assessment of cellular interactions and their role in DR. This is further supported by the recent data showing down-regulation of connexin 43 gap junctions along the vascular relay from capillary to feeding arteriole as one of the earliest indicators of experimental DR, with rippling consequences to the anatomical and physiological integrity of the retina. Here, recent advancements in our knowledge of mechanisms controlling the retinal neurovascular unit will be assessed, along with their implications for future treatment and diagnosis of DR.

During development, neurons navigate a tangled thicket of thousands of axons and dendrites to synapse with just a few specific targets. This phenomenon termed wiring specificity, is critical to the assembly of neural circuits and the way neurons manage this feat is only now becoming clear. Recent studies in the mouse retina are shedding new insight into this process. They show that specific wiring arises through a series of stages that include: directed axonal and dendritic growth, the formation of neuropil layers, positioning of such layers, and matching of co-laminar synaptic partners. Each stage appears to be directed by a distinct family of recognition molecules, suggesting that the combinatorial expression of such family members might act as a blueprint for retinal connectivity. By reviewing the evidence in support of each stage, and by considering their underlying molecular mechanisms, we attempt to synthesize these results into a wiring model which generates testable predictions for future studies. Finally, we conclude by highlighting new optical methods that could be used to address such predictions and gain further insight into this fundamental process., (Copyright © 2020 Rangel Olguin, Rochon and Krishnaswamy.)

The ciliary marginal zone (CMZ) of the zebrafish retina contains a population of actively proliferating resident stem cells, which generate retinal neurons throughout life. The maintenance methyltransferase, dnmt1, is expressed within the CMZ. Loss of dnmt1 function results in gene misregulation and cell death in a variety of developmental contexts, however, its role in retinal stem cell (RSC) maintenance is currently unknown. Here, we demonstrate that zebrafish dnmt1 s872 mutants possess severe defects in RSC maintenance within the CMZ. Using a combination of immunohistochemistry, in situ hybridization, and a transgenic reporter assay, our results demonstrate a requirement for dnmt1 activity in the regulation of RSC proliferation, gene expression and in the repression of endogenous retroelements (REs). Ultimately, cell death is elevated in the dnmt1 -/- CMZ, but in a p53-independent manner. Using a transgenic reporter for RE transposition activity, we demonstrate increased transposition in the dnmt1 -/- CMZ. Taken together our data identify a critical role for dnmt1 function in RSC maintenance in the vertebrate eye.

Zebrafish have the ability to regenerate damaged cells and tissues by activating quiescent stem and progenitor cells or reprogramming differentiated cells into regeneration-competent precursors. Proliferation among the cells that will functionally restore injured tissues is a fundamental biological process underlying regeneration. Midkine-a is a cytokine growth factor, whose expression is strongly induced by injury in a variety of tissues across a range of vertebrate classes. Using a zebrafish Midkine-a loss of function mutant, we evaluated regeneration of caudal fin, extraocular muscle and retinal neurons to investigate the function of Midkine-a during epimorphic regeneration. In wildtype zebrafish, injury among these tissues induces robust proliferation and rapid regeneration. In Midkine-a mutants, the initial proliferation in each of these tissues is significantly diminished or absent. Regeneration of the caudal fin and extraocular muscle is delayed; regeneration of the retina is nearly completely absent. These data demonstrate that Midkine-a is universally required in the signaling pathways that convert tissue injury into the initial burst of cell proliferation. Further, these data highlight differences in the molecular mechanisms that regulate epimorphic regeneration in zebrafish., Competing Interests: The authors have declared that no competing interests exist.

Degeneration of specific retinal neurons in diseases like glaucoma, age-related macular degeneration, and retinitis pigmentosa is the leading cause of irreversible blindness. Currently, there is no therapy to modify the disease-associated degenerative changes. With the advancement in our knowledge about the mechanisms that regulate the development of the vertebrate retina, the approach to treat blinding diseases through regenerative medicine appears a near possibility. Recapitulation of developmental mechanisms is critical for reproducibly generating cells in either 2D or 3D culture of pluripotent stem cells for retinal repair and disease modeling. It is the key for unlocking the neurogenic potential of Müller glia in the adult retina for therapeutic regeneration. Here, we examine the current status and potential of the regenerative medicine approach for the retina in the backdrop of developmental mechanisms., Competing Interests: Declaration of competing interest The authors declare no competing or financial interests., (Copyright © 2019. Published by Elsevier Ltd.)

Objectives: Abnormal retina structures, such as thinner retinal nerve fiber layer (RNFL), have been frequently reported in patients with Alzheimer's disease (AD). However, the association between RNFL and brain structures in cognitively normal adults remains unknown. We therefore set out to conduct a cross-sectional investigation to determine whether RNFL thickness is associated with brain structure volumes in nondemented older adults., Methods: We measured RNFL thickness by optical coherence tomography and brain structure volumes by 3 T magnetic resonance imaging. Cognitive function was assessed using the Chinese version of Repeatable Battery for the Assessment of Neurological Status. Pearson correlation was initially employed to screen for the potential associations among RNFL thickness, brain structure volumes and cognitive function. And then, multivariable linear regression models were conducted to further examine such associations adjusting for possible confounding factors, including age, sex, years of education and the estimated total intracranial volume (eTIV)., Results: 113 participants (≥ 65 years old) were screened and 80 of them (mean age: 68 ± 5.3 years; 48% male) were included in the final analysis. RNFL thickness in temporal quadrant was associated with medial temporal lobes volumes [unadjusted: r = 0.155, P = 0.175; adjusted: β = 0.205 (0.014, 0.383), P = 0.035], and especially associated with the hippocampus volume [unadjusted: r = 0.213, P = 0.062; adjusted: β = 0.251 (0.060, 0.435), P = 0.011] after adjusted for age, sex, years of education and eTIV. Moreover, it showed that RNFL thickness in inferior quadrant [unadjusted: r = 0.221, P = 0.052; adjusted: β = 0.226 (0.010. 0.446), P = 0.041] was significantly associated with occipital lobes volumes after the adjustment of age, sex, years of education and eTIV, and selectively associated with the substructure of lingual gyrus volume [unadjusted: r = 0.223, P = 0.050; adjusted: β = 0.278 (0.058, 0.487), P = 0.014]. In addition, average RNFL thickness was associated with the cognitive domain of visuospatial/constructional [unadjusted: r = 0.114, P = 0.322; adjusted: β = 0.216 (0.006, 0.426), P = 0.044] after the adjustment in these nondemented older adults., Conclusions: Quadrant-specific associations exist between RNFL thickness and brain regions vulnerable to aging or neurodegeneration in older adults with normal cognition. These findings would promote further investigations into using RNFL as a noninvasive and less expensive biomarker of neurocognitive aging and AD-related neurodegeneration., Competing Interests: Declaration of Competing Interest All authors claim that there are no conflicts of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Previous electroencephalographic research on attentional salience did not fully capture the complexities of low-level vision, which relies on both cone-opponent chromatic and cone-additive luminance mechanisms. We systematically varied color and luminance contrast using a visual search task for a higher contrast target to assess the degree to which the salience-computing attentional mechanisms are constrained by low-level visual inputs. In our first experiment, stimuli were defined by contrast that isolated chromatic or luminance mechanisms. In our second experiment, targets were defined by contrasts that isolated or combined achromatic and chromatic mechanisms. In both experiments, event-related potential waveforms contralateral and ipsilateral to the target were qualitatively different for chromatic- compared to luminance-defined stimuli. The same was true of the difference waves computed from these waveforms, with isoluminant stimuli eliciting a mid-latency posterior contralateral negativity (PCN) component and achromatic stimuli eliciting a complex of multiple components, including an early posterior contralateral positivity followed by a late-latency PCN. Combining color with luminance resulted in waveform and difference wave patterns equivalent to those of achromatic stimuli. When large levels of chromaticity contrast were added to targets with small levels of luminance contrast, PCN latency was speeded. In conclusion, the mechanisms underlying attentional salience are constrained by the low-level inputs they receive. Furthermore, speeded PCN latencies for stimuli that combine color and luminance signals compared to stimuli that contain luminance alone demonstrate that color and luminance channels are integrated during pre-attentive visual processing, before top-down allocation of attention is triggered.

Color constancy involves disambiguating the spectral characteristics of lights and surfaces, for example to distinguish red in white light from white in red light. Solving this problem appears especially challenging for bluish tints, which may be attributed more often to shading, and this bias may underlie the individual differences in whether people described the widely publicized image of #thedress as blue-black or white-gold. To probe these higher-level color inferences, we examined neural correlates of the blue-bias, using frequency-tagging and high-density electroencephalography to monitor responses to 3-Hz alternations between different color versions of #thedress. Specifically, we compared relative neural responses to the original "blue" dress image alternated with the complementary "yellow" image (formed by inverting the chromatic contrast of each pixel). This image pair produced a large modulation of the electroencephalography amplitude at the alternation frequency, consistent with a perceived contrast difference between the blue and yellow images. Furthermore, decoding topographical differences in the blue-yellow asymmetries over occipitoparietal channels predicted blue-black and white-gold observers with over 80% accuracy. The blue-yellow asymmetry was stronger than for a "red" versus "green" pair matched for the same component differences in L versus M or S versus LM chromatic contrast as the blue-yellow pair and thus cannot be accounted for by asymmetries within either precortical cardinal mechanism. Instead, the results may point to neural correlates of a higher-level perceptual representation of surface colors.

Retinal degeneration is a leading cause of untreatable blindness in the industrialised world. It is typically irreversible and there are few curative treatments available. The use of stem cells to generate new retinal neurons for transplantation purposes has received significant interest in recent years and is beginning to move towards clinical trials. However, such approaches are likely to be most effective for relatively focal areas of repair. An intriguing complementary approach is endogenous self-repair. Retinal cells from the ciliary marginal zone (CMZ), retinal pigment epithelium (RPE) and Müller glial cells (MG) have all been shown to play a role in retinal repair, typically in lower vertebrates. Among them, MG have received renewed interest, due to their distribution throughout (centre to periphery) the neural retina and their potential to re-acquire a progenitor-like state following retinal injury with the ability to proliferate and generate new neurons. Triggering these innate self-repair mechanisms represents an exciting therapeutic option in treating retinal degeneration. However, these cells behave differently in mammalian and non-mammalian species, with a considerably restricted potential in mammals. In this short review, we look at some of the recent progress made in our understanding of the signalling pathways that underlie MG-mediated regeneration in lower vertebrates, and some of the challenges that have been revealed in our attempts to reactivate this process in the mammalian retina.

During development, newly-differentiated neurons undergo several morphological and physiological changes to become functional, mature neurons. Physiologic maturation of neuronal cells derived from isolated stem or progenitor cells may provide insight into maturation in vivo but is not well studied. As a step towards understanding how neuronal maturation is regulated, we studied the developmental switch of response to the neurotransmitter GABA, from excitatory depolarization to inhibitory hyperpolarization. We compared acutely isolated retinal ganglion cells (RGCs) at various developmental stages and RGCs differentiated in vitro from embryonic retinal progenitors for the effects of aging and, independently, of retinal environment age on their GABA A receptor (GABA A R) responses, elicited by muscimol. We found that neurons generated in vitro from progenitors exhibited depolarizing, immature GABA responses, like those of early postnatal RGCs. As progenitor-derived neurons aged from 1 to 3 weeks, their GABA responses matured. Interestingly, signals secreted by the early postnatal retina suppressed acquisition of mature GABA responses. This suppression was not associated with changes in expression of GABA A R or of the chloride co-transporter KCC2, but rather with inhibition of KCC2 dimerization in differentiating neurons. Taken together, these data indicate GABA response maturation depends on release of inhibition by developmentally regulated diffusible signals from the retina.

Visual motion estimation is a canonical neural computation. In Drosophila, recent advances have identified anatomic and functional circuitry underlying direction-selective computations. Models with varying levels of abstraction have been proposed to explain specific experimental results but have rarely been compared across experiments. Here we use the wealth of available anatomical and physiological data to construct a minimal, biophysically inspired synaptic model for Drosophila's first-order direction-selective T4 cells. We show how this model relates mathematically to classical models of motion detection, including the Hassenstein-Reichardt correlator model. We used numerical simulation to test how well this synaptic model could reproduce measurements of T4 cells across many datasets and stimulus modalities. These comparisons include responses to sinusoid gratings, to apparent motion stimuli, to stochastic stimuli, and to natural scenes. Without fine-tuning this model, it sufficed to reproduce many, but not all, response properties of T4 cells. Since this model is flexible and based on straightforward biophysical properties, it provides an extensible framework for developing a mechanistic understanding of T4 neural response properties. Moreover, it can be used to assess the sufficiency of simple biophysical mechanisms to describe features of the direction-selective computation and identify where our understanding must be improved.

The vertebrate retina first evolved some 500 million years ago in ancestral marine chordates. Since then, the eyes of different species have been tuned to best support their unique visuoecological lifestyles. Visual specializations in eye designs, large-scale inhomogeneities across the retinal surface and local circuit motifs mean that all species' retinas are unique. Computational theories, such as the efficient coding hypothesis, have come a long way towards an explanation of the basic features of retinal organization and function; however, they cannot explain the full extent of retinal diversity within and across species. To build a truly general understanding of vertebrate vision and the retina's computational purpose, it is therefore important to more quantitatively relate different species' retinal functions to their specific natural environments and behavioural requirements. Ultimately, the goal of such efforts should be to build up to a more general theory of vision.

Glaucoma is the most common neurodegenerative cause of irreversible blindness worldwide. Restricted caloric regimens are an attractive approach for delaying the progression of neurodegenerative diseases. Here we review the current literature on the effects of caloric restriction on retinal neurons, under physiological and pathological conditions. We focused on autophagy as one of the mechanisms modulated by restricted caloric regimens and involved in the death of retinal ganglion cells (RGCs) over the course of glaucoma., (© 2020 Elsevier B.V. All rights reserved.)

A coherent percept of our visual world is important for functioning. Ambiguities, however, are implicit in visual neural representations and must be resolved for stable perception of objects and scenes. Grouping processes can link multiple neurally ambiguous fragments across the visual field. Experiments here determined how multiple visual features of each fragment contribute to perceptual resolution of ambiguity by grouping. Chromatic interocular-switch rivalry, a technique for presenting competing dichoptic images, was used to induce ambiguous neural representations for equiluminant chromatic discs and gratings. Two dichoptic stimuli were presented simultaneously to measure the amount of time they both appeared the same in at least one feature domain. The two stimuli were grouped when they appeared to share ambiguous features such as color, orientation, and spatial frequency more often than chance. Experiments here tested whether unshared and unambiguous features impeded grouping of the ambiguous components. Overall, the results show that grouping can be driven by neural ambiguity that is common for fragments across the visual field, even when the fragments also have other unshared, unambiguous features.

Retinal function has long been studied with psychophysical methods in humans, whereas detailed functional studies of vision have been conducted mostly in animals owing to the invasive nature of physiological approaches. There are exceptions to this generalization, for example, the electroretinogram. This review examines exciting recent advances using in vivo retinal imaging to understand the function of retinal neurons. In some cases, the methods have existed for years and are still being optimized. In others, new methods such as optophysiology are revealing novel patterns of retinal function in animal models that have the potential to change our understanding of the functional capacity of the retina. Together, the advances in retinal imaging mark an important milestone that shifts attention away from anatomy alone and begins to probe the function of healthy and diseased eyes.

An animal's motion through the environment can induce large and frequent fluctuations in light intensity on the retina. These fluctuations pose a major challenge to neural circuits tasked with encoding visual information, as they can cause cells to adapt and lose sensitivity. Here, we report that sensitization, a short-term plasticity mechanism, solves this difficult computational problem by maintaining neuronal sensitivity in the face of these fluctuations. The numerically dominant output pathway in the macaque monkey retina, the midget (parvocellular-projecting) pathway, undergoes sensitization under specific conditions, including simulated eye movements. Sensitization is present in the excitatory synaptic inputs from midget bipolar cells and is mediated by presynaptic disinhibition from a wide-field mechanism extending >0.5 mm along the retinal surface. Direct physiological recordings and a computational model indicate that sensitization in the midget pathway supports accurate sensory encoding and prevents a loss of responsiveness during dynamic visual processing.

In this review, we summarize studies investigating the types and distribution of voltage- and calcium-gated ion channels in the different classes of retinal neurons: rods, cones, horizontal cells, bipolar cells, amacrine cells, interplexiform cells, and ganglion cells. We discuss differences among cell subtypes within these major cell classes, as well as differences among species, and consider how different ion channels shape the responses of different neurons. For example, even though second-order bipolar and horizontal cells do not typically generate fast sodium-dependent action potentials, many of these cells nevertheless possess fast sodium currents that can enhance their kinetic response capabilities. Ca 2+ channel activity can also shape response kinetics as well as regulating synaptic release. The L-type Ca 2+ channel subtype, Ca V 1.4, expressed in photoreceptor cells exhibits specific properties matching the particular needs of these cells such as limited inactivation which allows sustained channel activity and maintained synaptic release in darkness. The particular properties of K + and Cl - channels in different retinal neurons shape resting membrane potentials, response kinetics and spiking behavior. A remaining challenge is to characterize the specific distributions of ion channels in the more than 100 individual cell types that have been identified in the retina and to describe how these particular ion channels sculpt neuronal responses to assist in the processing of visual information by the retina., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Visual communication is used widely across the animal kingdom to convey crucial information about an animals' identity, reproductive status, and sex. Although it is well-demonstrated that auditory and olfactory sensitivity can change with reproductive state, fewer studies have tested for plasticity in the visual system, a surprising detail since courtship and mate choice behaviors in many species are largely dependent on visual signals. Here, we tested for reproductive state-dependent plasticity in the eye of the cichlid fish Astatotilapia burtoni using behavioral, gene expression, neural activation, and electrophysiology techniques. Males court ovulated females more intensely than gravid females, and ovulated females were more responsive to male courtship behaviors than gravid females. Using electroretinography to measure visual sensitivity in dark-adapted fish, we revealed that gravid, reproductively-ready females have increased visual sensitivity at wavelengths associated with male courtship coloration compared to non-gravid females. After ovulation was hormonally induced, female's spectral sensitivity further increased compared to pre-injection measurements. This increased sensitivity after hormone injection was absent in non-gravid females and in males, suggesting an ovulation-triggered increase in visual sensitivity. Ovulated females had higher mRNA expression levels of reproductive neuromodulatory receptors (sex-steroids; gonadotropins) in the eye than nonovulated females, whereas males had similar expression levels independent of reproductive/social state. In addition, female mate choice-like behaviors positively correlated with expression of gonadotropin system receptors in the eye. Collectively, these data provide crucial evidence linking endocrine modulation of visual plasticity to mate choice behaviors in females., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Diabetic retinopathy, a leading cause of vision loss, was considered as a solely vascular disorder but some recent studies suggest that retinal neurons may be affected much before the appearance of vascular lesions. However, the cellular processes involved in diabetes-induced degeneration of retinal neurons are poorly understood. Calcium (Ca 2+ ) signaling plays a key role in normal functioning of neurons, and its dysregulation may lead to degeneration of neurons. Mitochondria are crucial components involved in the regulation of intracellular Ca 2+ signaling. In this study, we have investigated the effects of diabetes on Ca 2+ signaling in retinal neurons. The study was performed in rat retinal neurons cultured in high glucose condition (HGC) for 7-14 days and in acutely prepared retinal slices isolated from diabetic rats. When Ca 2+ influx was induced by depolarization of neurons with 60 mM KCl in HGC neurons, the Ca 2+ rise was sustained for a much longer duration as compared to controls, suggesting perturbation of Ca 2+ buffering. In addition, HGC neurons also showed notably enhanced Ca 2+ load in the mitochondria, which was accompanied by depolarization of mitochondrial membrane and enhanced reactive oxygen species formation. Similar results were obtained in acutely prepared retinal slices from control and diabetic rats. The depolarization of mitochondrial membrane was more pronounced in the neurons of the inner nuclear layer of diabetic rats. The physiological changes in mitochondria were observed as early as 9 weeks post diabetes induction. Thus, we report here that the intracellular Ca 2+ signaling and mitochondrial function in retinal neurons are altered at an early stage of diabetes., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)

Many neurodegenerations, including those of the visual system, have complex etiologies that include roles for both neurons and glia. In the retina there is evidence that retinal astrocytes play an important role in neurodegeneration. There are several approaches for isolating and growing primary retinal astrocytes, however, they often lead to different results. In this study, we examined the influence of culture conditions on phenotypic maturation of primary, purified retinal glia. We compared retinal astrocytes and Müller glia purified by immunomagnetic separation, as differentiation between these astrocyte subtypes is critical and immuno-based methods are the standard practice of purification. We found that while time in culture impacts the health and phenotype of both astrocytes and Müller glia, the phenotypic maturation of retinal astrocytes was most impacted by serum factors. These factors appeared to actively regulate intermediate filament phenotypes in a manner consistent with the induction of astrocyte-mesenchymal transition (AMT). This propensity for retinal astrocytes to shift along an AMT continuum should be considered when interpreting resulting data. Our goal is that this study will help standardize the field so that studies are replicable, comparable, and as accurate as possible for subsequent interpretation of findings., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Zebrafish have the remarkable capacity to regenerate retinal neurons following a variety of damage paradigms. Following initial tissue insult and a period of cell death, a proliferative phase ensues that generates neuronal progenitors, which ultimately regenerate damaged neurons. Recent work has revealed that Müller glia are the source of regenerated neurons in zebrafish. However, the roles of another important class of glia present in the retina, microglia, during this regenerative phase remain elusive. Here, we examine retinal tissue and perform QuantSeq. 3'mRNA sequencing/transcriptome analysis to reveal localization and putative functions, respectively, of mpeg1 expressing cells (microglia/macrophages) during Müller glia-mediated regeneration, corresponding to a time of progenitor proliferation and production of new neurons. Our results indicate that in this regenerative state, mpeg1-expressing cells are located in regions containing regenerative Müller glia and are likely engaged in active vesicle trafficking. Further, mpeg1+ cells congregate at and around the optic nerve head. Our transcriptome analysis reveals several novel genes not previously described in microglia. This dataset represents the first report, to our knowledge, to use RNA sequencing to probe the microglial transcriptome in such context, and therefore provides a resource towards understanding microglia/macrophage function during successful retinal (and central nervous tissue) regeneration.

BACKGROUND The aim of this study was to assess and compare peripapillary retinal nerve fiber layer (RNFL) thickness in patients with Alzheimer's disease (AD), primary open-angle glaucoma (POAG), preperimetric glaucoma (PPG), and healthy controls with the use of Spectral Domain Optical Coherence Tomography (SD-OCT). MATERIAL AND METHODS Thirty patients with AD, 30 patients with POAG, 30 patients with PPG, and 30 healthy controls were enrolled in this cross-sectional study. Only 1 randomly selected eye of each patient was analyzed. Every subject underwent a thorough ophthalmological examination and OCT of the optic disc. The peripapillary RNFL thickness in each of the 6 sectors and globally was analyzed. RESULTS The RNFL was thinnest in patients with POAG. The mean RNFL thickness value was 60.97±12.97 µm and it was significantly lower than in healthy controls (106.30±8.95 µm), patients with PPG (93.20±12.04 µm), and AD patients (95.73±13.52 µm). Mean RNFL thickness in patients with AD was significantly lower when compared to healthy controls, and was higher compared to eyes with POAG, while there were no significant differences compared to patients with PPG. CONCLUSIONS Neuronal damage in the central nervous system (CNS) also affects to retinal axons. A major problem is to distinguish the cause for a moderate decrease in the RNFL thickness. This is particularly true for patients with glaucoma who have not been diagnosed with changes in the visual field. It is not possible to distinguish the cause of a mild decrease in the RNFL thickness based on the SD-OCT. This may result in misdiagnosis of glaucoma, unnecessary use of anti-glaucoma eye drops, and a delayed diagnosis of AD.

Measuring the color tuning of visual neurons is important for understanding the neural basis of vision, but it is challenging because of the inherently three-dimensional nature of color. Color tuning cannot be represented by a one-dimensional curve, and measuring three-dimensional tuning curves is difficult. One approach to addressing this challenge is to analyze neuronal color tuning data through the lens of mathematical models that make assumptions about the shapes of tuning curves. In this paper, we discuss the linear-nonlinear cascade model as a platform for measuring neuronal color tuning. We compare fitting this model by three techniques: two using response-weighted averaging and one using numerical optimization of likelihood. We highlight the advantages and disadvantages of each technique and emphasize the effects of the stimulus distribution on color tuning measurements., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Chromaticity type horizontal cells (C-type HCs) are the first retinal neurons exhibiting spectral information processing in cold-blooded vertebrates. The simple input of hyperpolarizing responses of cone photoreceptors is transformed in the C-type HCs into spectral opponent output. Nitric oxide (NO), a known background neuromodulator in the distal retina, was tested here for its effects upon spectral information processing by C-type HCs in the retina of turtle. Photoresponses were intracellularly recorded from C-type HCs, using light stimuli of different wavelength, applied over backgrounds of different wavelengths, and changing retinal NO level. Raising retinal level of NO in darkness by adding the precursor for its synthesis (l-Arginine) augmented the depolarizing photoresponses elicited by long-wavelength light stimuli, and reduced the hyperpolarizing photoresponses elicited by short-wavelength light stimuli. Lowering retinal level of NO by l-NAME, an inhibitor of NO synthesis, induced the opposite effects. However, the total voltage range of operation remained constant regardless of the level of NO. Qualitatively similar effects were observed under background illuminations regardless of background strength and wavelength. Altering retinal level of NO exerted a small effect upon the null wavelength. Our findings are consistent with the known effects of NO upon turtle distal retinal neurons, with the addition of NO strengthening the negative feedback pathway from L-type horizontal cells onto medium-wavelength cones., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Distinct neuronal types connect in complex ways to generate functional neural circuits. The molecular diversity required to specify this connectivity could be supplied by multigene families of synaptic recognition molecules, but most studies to date have assessed just one or a few members at a time. Here, we analyze roles of cadherins (Cdhs) in formation of retinal circuits comprising eight neuronal types that inform the brain about motion in four directions. We show that at least 15 classical Cdhs are expressed by neurons in these circuits and at least 6 (Cdh6-10 and 18) act individually or in combinations to promote specific connectivity among the cells. They act in part by directing the processes of output neurons and excitatory interneurons to a cellular scaffold formed by inhibitory interneurons. Because Cdhs are expressed combinatorially by many central neurons, similar interactions could be involved in patterning circuits throughout the brain., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Microglia, the primary resident immune cell type, constitute a key population of glia in the retina. Recent evidence indicates that microglia play significant functional roles in the retina at different life stages. During development, retinal microglia regulate neuronal survival by exerting trophic influences and influencing programmed cell death. During adulthood, ramified microglia in the plexiform layers interact closely with synapses to maintain synaptic structure and function that underlie the retina's electrophysiological response to light. Under pathological conditions, retinal microglia participate in potentiating neurodegeneration in diseases such as glaucoma, retinitis pigmentosa, and age-related neurodegeneration by producing proinflammatory neurotoxic cytokines and removing living neurons via phagocytosis. Modulation of pathogenic microglial activation states and effector mechanisms has been linked to neuroprotection in animal models of retinal diseases. These findings have led to the design of early proof-of-concept clinical trials with microglial modulation as a therapeutic strategy.

The thalamocortical pathway is the main route of communication between the eye and the cerebral cortex. During embryonic development, thalamocortical afferents travel to L4 and are sorted by receptive field position, eye of origin, and contrast polarity (i.e., preference for light or dark stimuli). In primates and carnivores, this sorting involves numerous afferents, most of which sample a limited region of the binocular field. Devoting abundant thalamocortical resources to process a limited visual field has a clear advantage: It allows many stimulus combinations to be sampled at each spatial location. Moreover, the sampling efficiency can be further enhanced by organizing the afferents in a cortical grid for eye input and contrast polarity. We argue that thalamocortical interactions within this eye-polarity grid can be used to represent multiple stimulus combinations found in nature and to build an accurate cortical map for multidimensional stimulus space.

Visual motion on the retina activates a cohort of retinal ganglion cells (RGCs). This population activity encodes multiple streams of information extracted by parallel retinal circuits. Motion processing in the retina is best studied in the direction-selective circuit. The main focus of this review is the neural basis of direction selectivity, which has been investigated in unprecedented detail using state-of-the-art functional, connectomic, and modeling methods. Mechanisms underlying the encoding of other motion features by broader RGC populations are also discussed. Recent discoveries at both single-cell and population levels highlight the dynamic and stimulus-dependent engagement of multiple mechanisms that collectively implement robust motion detection under diverse visual conditions.

We propose a coupled convolution layer comprising multiple parallel convolutions with mutually constrained filters. Inspired by biological human vision mechanism, we constrain the convolution filters such that one set of filter weights should be geometrically rotated, mirrored, or be the negative of the other. Our analysis suggests that the coupled convolution layer is more effective for lower layer where feature maps preserve geometric properties. Experimental comparisons demonstrate that the proposed coupled convolution layer performs slightly better than the original layer while decreasing the number of parameters. We evaluate its effect compared to non-constrained convolution layer using the CIFAR-10, CIFAR-100, and PlanktonSet 1.0 datasets., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aims/objective: The present study aimed to explore the effects of micro-ribonucleic acid-365 (miR-365) on apoptosis of retinal neurons by targeting insulin-like growth factor-1 (IGF-1) in diabetes mellitus rats., Materials and Methods: High glucose-induced retinal neurons were assigned into the blank (with no plasmid transfection), negative control (with plasmid transfection), anti-miR-365 (transfected miR-365 antagomir), transfected IGF-1 short hairpin RNA plasmid (sh-IGF-1) and transfected miR-365 antagomir and IGF-1 shRNA plasmid (anti-miR-365 + sh-IGF-1) groups. Proliferation and apoptosis of retinal neurons were detected by 5-ethynyl-2'-deoxyuridine assay and Hoechst 33342 staining, respectively. Expressions of miR-365, IGF-1, Bcl-2-associated X protein (Bax) and Bcl-2 were determined by reverse transcription quantitative polymerase chain reaction and western blotting. A control group contained 10 healthy rats. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining was used to evaluate apoptosis of retinal neurons in rats., Results: In the anti-miR-365 group, the apoptosis rate and Bax expression were reduced in comparison with the negative control and blank groups, whereas the sh-IGF-1 and anti-miR-365 + sh-IGF-1 groups presented an opposite trend. Compared with the normal group, expressions of miR-365 and Bax were increased, and expressions of IGF-1 and Bcl-2 were decreased, with more apoptotic cells in diabetes mellitus rat models. The sh-IGF-1 group had lower Bax expression, and higher expressions of IGF-1 and Bcl-2 with fewer apoptotic cells. Additionally, Bax expression was upregulated, expressions of IGF-1 and Bcl-2 were downregulated, and apoptotic cells were higher in the anti-miR-365 + sh-IGF-1 groups than the anti-miR-365 group., Conclusion: The results of the present study suggest that suppressed miR-365 increases the IGF-1 expression, leading to anti-apoptotic effects on retinal neurons in diabetic rats., (© 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Circuit operations are determined jointly by the properties of the circuit elements and the properties of the connections among these elements. In the nervous system, neurons exhibit diverse morphologies and branching patterns, allowing rich compartmentalization within individual cells and complex synaptic interactions among groups of cells. In this review, we summarize work detailing how neuronal morphology impacts neural circuit function. In particular, we consider example neurons in the retina, cerebral cortex, and the stomatogastric ganglion of crustaceans. We also explore molecular coregulators of morphology and circuit function to begin bridging the gap between molecular and systems approaches. By identifying motifs in different systems, we move closer to understanding the structure-function relationships that are present in neural circuits.

Many animals rely on vision to detect, locate, and track moving objects. In Drosophila courtship, males primarily use visual cues to orient toward and follow females and to select the ipsilateral wing for courtship song. Here, we show that the LC10 visual projection neurons convey essential visual information during courtship. Males with LC10 neurons silenced are unable to orient toward or maintain proximity to the female and do not predominantly use the ipsilateral wing when singing. LC10 neurons preferentially respond to small moving objects using an antagonistic motion-based center-surround mechanism. Unilateral activation of LC10 neurons recapitulates the orienting and ipsilateral wing extension normally elicited by females, and the potency with which LC10 induces wing extension is enhanced in a state of courtship arousal controlled by male-specific P1 neurons. These data suggest that LC10 is a major pathway relaying visual input to the courtship circuits in the male brain., (Copyright © 2018 Elsevier Inc. All rights reserved.)