AAV11 permits efficient retrograde targeting of projection neurons

Viral tracers that permit efficient retrograde targeting of projection neurons are powerful vehicles for structural and functional dissections of the neural circuit and for the treatment of brain diseases. Recombinant adeno-associated viruses (rAAVs) are the most potential candidates because they are low-toxic with high-level transgene expression and minimal host immune responses. Currently, some rAAVs based on capsid engineering for retrograde tracing have been widely used in the analysis and manipulation of neural circuits, but suffer from brain area selectivity and inefficient retrograde transduction in certain neural connections. Here, we discovered that the recombinant adeno-associated virus 11 (rAAV11) exhibits potent retrograde labeling of projection neurons with enhanced efficiency to rAAV2-retro in some neural connections. Combined with calcium recording technology, rAAV11 can be used to monitor neuronal activities by expressing Cre recombinase or calcium-sensitive functional probe. In addition, we further showed the suitability of rAAV11 for astrocyte targeting. These properties make rAAV11 a promising tool for the mapping and manipulation of neural circuits and gene therapy of some neurological and neurodegenerative disorders.

mtIF3 is locally translated in axons and regulates mitochondrial translation for axonal growth

Background The establishment and maintenance of functional neural connections relies on appropriate distribution and localization of mitochondria in neurites, as these organelles provide essential energy and metabolites. In particular, mitochondria are transported to axons and support local energy production to maintain energy-demanding neuronal processes including axon branching, growth, and regeneration. Additionally, local protein synthesis is required for structural and functional changes in axons, with nuclear-encoded mitochondrial mRNAs having been found localized in axons. However, it remains unclear whether these mRNAs are locally translated and whether the potential translated mitochondrial proteins are involved in the regulation of mitochondrial functions in axons. Here, we aim to further understand the purpose of such compartmentalization by focusing on the role of mitochondrial initiation factor 3 (mtIF3), whose nuclear-encoded transcripts have been shown to be present in axonal growth cones. Results We demonstrate that brain-derived neurotrophic factor (BDNF) induces local translation of mtIF3 mRNA in axonal growth cones. Subsequently, mtIF3 protein is translocated into axonal mitochondria and promotes mitochondrial translation as assessed by our newly developed bimolecular fluorescence complementation sensor for the assembly of mitochondrial ribosomes. We further show that BDNF-induced axonal growth requires mtIF3-dependent mitochondrial translation in distal axons. Conclusion We describe a previously unknown function of mitochondrial initiation factor 3 (mtIF3) in axonal protein synthesis and development. These findings provide insight into the way neurons adaptively control mitochondrial physiology and axonal development via local mtIF3 translation.

Physical Fitness on Academic Performance in Youth

Physical fitness, as an important physical health issue, may play a key role also in brain health by affecting the academic performance of youth helping the cognitive control components to improve. Memory and cognitive skill are some of the cognitive control components that are fundamental even for academic ability. Aim: In this context, the aim of our study was to investigate and analyze the facts regarding the potential of the exercises on academic achievement improvement. Methods: In order to realize a detailed review study we used the Jab Ref as a research sector, focusing more on navigating the Medline, Google Scholar, and Inspire options that this program contains. While as the selection criteria of the collected scientific articles, we used the keywords that provided us the exact articles that stated facts about the aim of our study. Results: Authors emphasized that the development of motor skills by practicing the coordinative exercises may have a beneficial influence on the learning process improving academic performance. This comes out because of the coordinative exercise’s impact on increasing the number of neuron transmitters and the new neural connections that enable youth to have a better perception regarding motor and academic situations. In addition, the authors underline the fact that the most active youth tend to perform better academically.

Multi-Frequency Image Completion via a Biologically-Inspired Sub-Riemannian Model with Frequency and Phase

We present a novel cortically-inspired image completion algorithm. It uses five-dimensional sub-Riemannian cortical geometry, modeling the orientation, spatial frequency and phase-selective behavior of the cells in the visual cortex. The algorithm extracts the orientation, frequency and phase information existing in a given two-dimensional corrupted input image via a Gabor transform and represents those values in terms of cortical cell output responses in the model geometry. Then, it performs completion via a diffusion concentrated in a neighborhood along the neural connections within the model geometry. The diffusion models the activity propagation integrating orientation, frequency and phase features along the neural connections. Finally, the algorithm transforms the diffused and completed output responses back to the two-dimensional image plane.

Jogos de Estafetas Desenvolvimentistas Cognitivos

O modelo pedagógico para o ensino da educação física conhecido como Abordagem Desenvolvimentista tem na sua base teórica o enfoque na aquisição de habilidades motoras. Os jogos de estafetas são brincadeiras com base em corridas, onde cada participante deve percorrer um trajeto delimitado procurando realizá-lo no menor tempo possível. A proposta que segue, apresenta os Jogos de Estafetas Desenvolvimentistas Cognitivos. Quando conseguimos estabelecer conexões entre as tarefas motora e cognitiva, ampliando gradualmente a complexidade da atividade, estaremos contribuindo para o desenvolvimento de novas conexões neurais e estimulando a plasticidade cerebral. Os referidos jogos vêm sendo trabalhados com êxito por professores de Educação Física que atuam nas redes pública e privada de ensino da cidade de Caxias do Sul, sendo boas opções para as aulas de educação física na educação básica. The pedagogical model for teaching physical education known as the Developmental Approach has in its theoretical basis the focus on the acquisition of motor skills. The relay games are games based on races, where each participant must run a defined path trying to accomplish it in the shortest time possible. The following proposal presents the Cognitive Developmental Relay Games. When we can establish connections between motor and cognitive tasks, gradually increasing the complexity of the activity, we will be contributing to the development of new neural connections and stimulating brain plasticity. These games have been successfully used by physical education teachers in public and private schools in the city of Caxias do Sul, and are good options for physical education classes in basic education.

An Update on Graphene-Based Nanomaterials for Neural Growth and Central Nervous System Regeneration

Thanks to their reduced size, great surface area, and capacity to interact with cells and tissues, nanomaterials present some attractive biological and chemical characteristics with potential uses in the field of biomedical applications. In this context, graphene and its chemical derivatives have been extensively used in many biomedical research areas from drug delivery to bioelectronics and tissue engineering. Graphene-based nanomaterials show excellent optical, mechanical, and biological properties. They can be used as a substrate in the field of tissue engineering due to their conductivity, allowing to study, and educate neural connections, and guide neural growth and differentiation; thus, graphene-based nanomaterials represent an emerging aspect in regenerative medicine. Moreover, there is now an urgent need to develop multifunctional and functionalized nanomaterials able to arrive at neuronal cells through the blood-brain barrier, to manage a specific drug delivery system. In this review, we will focus on the recent applications of graphene-based nanomaterials in vitro and in vivo, also combining graphene with other smart materials to achieve the best benefits in the fields of nervous tissue engineering and neural regenerative medicine. We will then highlight the potential use of these graphene-based materials to construct graphene 3D scaffolds able to stimulate neural growth and regeneration in vivo for clinical applications.

Repeated intravenous infusion of mesenchymal stem cells for enhanced functional recovery in a rat model of chronic cerebral ischemia

OBJECTIVE Stroke is a major cause of long-term disability, and there are few effective treatments that improve function in patients during the chronic phase of stroke. Previous research has shown that single systemic infusion of mesenchymal stem cells (MSCs) improves motor function in acute and chronic cerebral ischemia models in rats. A possible mechanism that could explain such an event includes the enhanced neural connections between cerebral hemispheres that contribute to therapeutic effects. In the present study, repeated infusions (3 times at weekly intervals) of MSCs were administered in a rat model of chronic stroke to determine if multiple dosing facilitated plasticity in neural connections. METHODS The authors induced middle cerebral artery occlusion (MCAO) in rats and, 8 weeks thereafter, used them as a chronic stroke model. The rats with MCAO were randomized and intravenously infused with vehicle only (vehicle group); with MSCs at week 8 (single administration: MSC-1 group); or with MSCs at weeks 8, 9, and 10 (3 times, repeated administration: MSC-3 group) via femoral veins. Ischemic lesion volume and behavioral performance were examined. Fifteen weeks after induction of MCAO, the thickness of the corpus callosum (CC) was determined using Nissl staining. Immunohistochemical analysis of the CC was performed using anti-neurofilament antibody. Interhemispheric connections through the CC were assessed ex vivo by diffusion tensor imaging. RESULTS Motor recovery was better in the MSC-3 group than in the MSC-1 group. In each group, there was no change in the ischemic volume before and after infusion. However, both thickness and optical density of neurofilament staining in the CC were greater in the MSC-3 group, followed by the MSC-1 group, and then the vehicle group. The increased thickness and optical density of neurofilament in the CC correlated with motor function at 15 weeks following induction of MCAO. Preserved neural tracts that ran through interhemispheric connections via the CC were also more extensive in the MSC-3 group, followed by the MSC-1 group and then the vehicle group, as observed ex vivo using diffusion tensor imaging. CONCLUSIONS These results indicate that repeated systemic administration of MSCs over 3 weeks resulted in greater functional improvement as compared to single administration and/or vehicle infusion. In addition, administration of MSCs is associated with promotion of interhemispheric connectivity through the CC in the chronic phase of cerebral infarction.

Sequence learning attenuates cortical responses in both frontal and perceptual cortices in early infancy

Prior work using a variety of imaging modalities has found that the frontal lobe is involved in higher-order sequential and statistical learning in young infants. Separate lines of work have found evidence of modulation of posterior sensory cortices during and after learning tasks. How do these processes relate together? Here, we build from a well-regarded EEG task that found evidence that the frontal lobe of young infants tracked higher-order sequential information (Basirat et al., 2014) and ask whether posterior perceptual cortices respond differentially to predictable vs. unpredictable sequences as well. First, replicating and extending past work, we found evidence of frontal lobe involvement in this task. Second, consistent with our hypotheses, we found that there is a corresponding attenuation of neural responses in the posterior perceptual cortices (temporal and occipital) to predictable compared to unpredictable audiovisual sequences. This study provides convergent evidence that the frontal lobe is crucial for higher-level learning in young infants but that it likely works as part of a large, distributed network of regions to modulate infant neural responses as a result of learning. Overall, this work challenges the view that the infant brain is not dynamic and disconnected, lacking in long-range neural connections. Instead, this paper reveals patterns of a highly dynamic and interconnected infant brain that change rapidly as a result of new, learnable experiences.

Associations of Irritability With Functional Connectivity of Amygdala and Nucleus Accumbens in Adolescents and Young Adults With ADHD

Objective Irritability is a common characteristic in ADHD. We examined whether dysfunction in neural connections supporting threat and reward processing was related to irritability in adolescents and young adults with ADHD. Method We used resting-state fMRI to assess connectivity of amygdala and nucleus accumbens seeds in those with ADHD ( n = 34) and an age- and gender-matched typically-developing comparison group ( n = 34). Results In those with ADHD, irritability was associated with atypical functional connectivity of both seed regions. Amygdala seeds showed greater connectivity with right inferior frontal gyrus and caudate/putamen, and less connectivity with precuneus. Nucleus accumbens seeds showed altered connectivity with middle temporal gyrus and precuneus. Conclusion The irritability-ADHD presentation is associated with atypical functional connectivity of reward and threat processing regions with cognitive control and emotion processing regions. These patterns provide novel evidence for irritability-associated neural underpinnings in adolescents and young adults with ADHD. The findings suggest cognitive and behavioral treatments that address response to reward, including omission of an expected reward and irritability, may be beneficial for ADHD.

Plasticity of Neural Connections Underlying Oxytocin-mediated Parental Behaviors of Male Mice

The adult brain can flexibly adapt behaviors to specific life-stage demands. For example, while sexually naïve male mice are aggressive to the conspecific young, they start to provide caregiving to infants around the time when their own young are expected. How such behavioral plasticity is implemented at the level of neural connections remains poorly understood. Using viral-genetic approaches, here we establish hypothalamic oxytocin neurons as key regulators of parental caregiving behaviors of male mice. We then used rabies virus-mediated unbiased screen to identify excitatory neural connections originating from the lateral hypothalamus to the oxytocin neurons to be drastically strengthened when male mice become fathers. These connections are functionally relevant, as their activation suppresses pup-directed aggression in virgin males. These results demonstrate the life-stage associated, long-distance, and cell-type-specific plasticity of neural connections in the hypothalamus, the brain region classically assumed to be hard-wired.