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Objective. The optic nerve is a good location for a visual neuroprosthesis. It can be targeted when a subject cannot receive a retinal prosthesis and it is less invasive than a cortical implant. The effectiveness of an electrical neuroprosthesis depends on the combination of the stimulation parameters which must be optimized, and an optimization strategy might be performing closed-loop stimulation using the evoked cortical response as feedback. However, it is necessary to identify target cortical activation patterns and to associate the cortical activity with the visual stimuli present in the visual field of the subjects. Visual stimuli decoding should be performed on large areas of the visual cortex, and with a method as translational as possible to shift the study to human subjects in the future. The aim of this work is to develop an algorithm that meets these requirements and can be leveraged to automatically associate a cortical activation pattern with the visual stimulus that generated it. Approach. Three mice were presented with ten different visual stimuli, and their primary visual cortex response was recorded using wide-field calcium imaging. Our decoding algorithm relies on a convolutional neural network (CNN), trained to classify the visual stimuli from the correspondent wide-field images. Several experiments were performed to identify the best training strategy and investigate the possibility of generalization. Main results. The best classification accuracy was 75.38% ± 4.77%, obtained pre-training the CNN on the MNIST digits dataset and fine-tuning it on our dataset. Generalization was possible pre-training the CNN to classify Mouse 1 dataset and fine-tuning it on Mouse 2 and Mouse 3, with accuracies of 64.14% ± 10.81% and 51.53% ± 6.48% respectively. Significance. The combination of wide-field calcium imaging and CNNs can be used to classify the cortical responses to simple visual stimuli and might be a viable alternative to existing decoding methodologies. It also allows us to consider the cortical activation as reliable feedback in future optic nerve stimulation experiments., (Creative Commons Attribution license.)

Autistic traits represent a continuum dimension across the population, with autism spectrum disorder (ASD) being the extreme end of the distribution. Accumulating evidence shows that neuroanatomical and neurofunctional profiles described in relatives of ASD individuals reflect an intermediate neurobiological pattern between the clinical population and healthy controls. This suggests that quantitative measures detecting autistic traits in the general population represent potential candidates for the development of biomarkers identifying early pathophysiological processes associated with ASD. Functional near-infrared spectroscopy (fNIRS) has been extensively employed to investigate neural development and function. In contrast, the potential of fNIRS to define reliable biomarkers of brain activity has been barely explored. Features of non-invasiveness, portability, ease of administration, and low-operating costs make fNIRS a suitable instrument to assess brain function for differential diagnosis, follow-up, analysis of treatment outcomes, and personalized medicine in several neurological conditions. Here, we introduce a novel standardized procedure with high entertaining value to measure hemodynamic responses (HDR) in the occipital cortex of adult subjects and children. We found that the variability of evoked HDR correlates with the autistic traits of children, assessed by the Autism-Spectrum Quotient. Interestingly, HDR amplitude was especially linked to social and communication features, representing the core symptoms of ASD. These findings establish a quick and easy strategy for measuring visually-evoked cortical activity with fNIRS that optimize the compliance of young subjects, setting the background for testing the diagnostic value of fNIRS visual measurements in the ASD clinical population., (© 2022. The Author(s).)

Exposing animals to an enriched environment (EE) has dramatic effects on brain structure, function, and plasticity. The poorly known "EE-derived signals'' mediating the EE effects are thought to be generated within the central nervous system. Here, we shift the focus to the body periphery, revealing that gut microbiota signals are crucial for EE-driven plasticity. Developmental analysis reveals striking differences in intestinal bacteria composition between EE and standard rearing (ST) mice, as well as enhanced levels of short-chain fatty acids (SCFA) in EE mice. Depleting the microbiota of EE mice with antibiotics strongly decreases SCFA and prevents activation of adult ocular dominance plasticity, spine dynamics, and microglia rearrangement. SCFA treatment in ST mice mimics EE induction of ocular dominance plasticity and microglial remodeling. Remarkably, transferring the microbiota of EE mice to ST recipients activates adult ocular dominance plasticity. Thus, experience-dependent changes in gut microbiota regulate brain plasticity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Visual cortical circuits show profound plasticity during early life and are later stabilized by molecular "brakes" limiting excessive rewiring beyond a critical period. The mechanisms coordinating the expression of these factors during the transition from development to adulthood remain unknown. We found that miR-29a expression in the visual cortex dramatically increases with age, but it is not experience-dependent. Precocious high levels of miR-29a blocked ocular dominance plasticity and caused an early appearance of perineuronal nets. Conversely, inhibition of miR-29a in adult mice using LNA antagomirs activated ocular dominance plasticity, reduced perineuronal nets, and restored their juvenile chemical composition. Activated adult plasticity had the typical functional and proteomic signature of critical period plasticity. Transcriptomic and proteomic studies indicated that miR-29a manipulation regulates the expression of plasticity brakes in specific cortical circuits. These data indicate that miR-29a is a regulator of the plasticity brakes promoting age-dependent stabilization of visual cortical connections., (© 2020 The Authors.)

Amblyopia is a neurodevelopmental disorder of the visual cortex arising from abnormal visual experience early in life which is a major cause of impaired vision in infants and young children (prevalence around 3.5%). Current treatments such as eye patching are ineffective in a large number of patients, especially when applied after the juvenile critical period. Physical exercise has been recently shown to enhance adult visual cortical plasticity and to promote visual acuity recovery. With the aim to understand the potentialities for translational applications, we investigated the effects of voluntary physical activity on recovery of depth perception in adult amblyopic rats with unrestricted binocular vision; visual acuity recovery was also assessed. We report that three weeks of voluntary physical activity (free running) induced a marked and long-lasting recovery of both depth perception and visual acuity. In the primary visual cortex, ocular dominance recovered both for excitatory and inhibitory cells and was linked to activation of a specific intracortical GABAergic circuit.

Retinitis Pigmentosa (RP) is a class of inherited disorders caused by the progressive death of photoreceptors in the retina. RP is still orphan of an effective treatment, with increasing optimism deriving from research aimed at arresting neurodegeneration or replacing light-responsive elements. All these therapeutic strategies rely on the functional integrity of the visual system downstream of photoreceptors. Whereas the inner retinal structure and optic radiation are known to be considerably preserved at least in early stages of RP, very little is known about the visual cortex. Remarkably, it remains completely unclear whether visual cortex plasticity is still present in RP. Using a well-established murine model of RP, the rd10 mouse, we report that visual cortical circuits retain high levels of plasticity, preserving their capability of input-dependent remodelling even at a late stage of retinal degeneration., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)

By virtue of their extensive axonal arborization and perisomatic synaptic targeting, cortical inhibitory parvalbumin (PV) cells strongly regulate principal cell output and plasticity and modulate experience-dependent refinement of cortical circuits during development. An interesting aspect of PV cell connectivity is its prolonged maturation time course, which is completed only by end of adolescence. The p75 neurotrophin receptor (p75NTR) regulates numerous cellular functions; however, its role on cortical circuit development and plasticity remains elusive, mainly because localizing p75NTR expression with cellular and temporal resolution has been challenging. By using RNAscope and a modified version of the proximity ligation assay, we found that p75NTR expression in PV cells decreases between the second and fourth postnatal week, at a time when PV cell synapse numbers increase dramatically. Conditional knockout of p75NTR in single PV neurons in vitro and in PV cell networks in vivo causes precocious formation of PV cell perisomatic innervation and perineural nets around PV cell somata, therefore suggesting that p75NTR expression modulates the timing of maturation of PV cell connectivity in the adolescent cortex. Remarkably, we found that PV cells still express p75NTR in adult mouse cortex of both sexes and that its activation is sufficient to destabilize PV cell connectivity and to restore cortical plasticity following monocular deprivation in vivo Together, our results show that p75NTR activation dynamically regulates PV cell connectivity, and represent a novel tool to foster brain plasticity in adults. SIGNIFICANCE STATEMENT In the cortex, inhibitory, GABA-releasing neurons control the output and plasticity of excitatory neurons. Within this diverse group, parvalbumin-expressing (PV) cells form the larger inhibitory system. PV cell connectivity develops slowly, reaching maturity only at the end of adolescence; however, the mechanisms controlling the timing of its maturation are not well understood. We discovered that the expression of the neurotrophin receptor p75NTR in PV cells inhibits the maturation of their connectivity in a cell-autonomous fashion, both in vitro and in vivo , and that p75NTR activation in adult PV cells promotes their remodeling and restores cortical plasticity. These results reveal a new p75NTR function in the regulation of the time course of PV cell maturation and in limiting cortical plasticity., (Copyright © 2019 the authors.)

MicroRNAs (miRNAs) are known to mediate post-transcriptional gene regulation, but their role in postnatal brain development is still poorly explored. We show that the expression of many miRNAs is dramatically regulated during functional maturation of the mouse visual cortex with miR-132/212 family being one of the top upregulated miRNAs. Age-downregulated transcripts are significantly enriched in miR-132/miR-212 putative targets and in genes upregulated in miR-132/212 null mice. At a functional level, miR-132/212 deletion affects development of receptive fields of cortical neurons determining a specific impairment of binocular matching of orientation preference, but leaving orientation and direction selectivity unaltered. This deficit is associated with reduced depth perception in the visual cliff test. Deletion of miR-132/212 from forebrain excitatory neurons replicates the binocular matching deficits. Thus, miR-132/212 family shapes the age-dependent transcriptome of the visual cortex during a specific developmental window resulting in maturation of binocular cortical cells and depth perception.