Project description:Visual processing depends on sensitive and balanced synaptic neurotransmission. Extracellular matrix proteins in the environment of cells are key modulators in synaptogenesis and synaptic plasticity. In the present study, we provide evidence that the combined loss of the four extracellular matrix components brevican, neurocan, tenascin-C and tenascin-R in quadruple knockout mice leads to severe retinal dysfunction and diminished visual motion processing in vivo. Remarkably, impaired visual motion processing was accompanied by a developmental loss of cholinergic direction-selective starburst amacrine cells. Additionally, we noted imbalance of inhibitory and excitatory synaptic signaling in the quadruple knockout retina. Collectively, the study offers novel insights into the functional importance of four key extracellular matrix proteins for retinal function, visual motion processing and synaptic signaling.
Project description:Visual processing depends on sensitive and balanced synaptic neurotransmission. Extracellular matrix proteins in the environment of cells are key modulators in synaptogenesis and synaptic plasticity. In the present study, we provide evidence that the combined loss of the four extracellular matrix components, brevican, neurocan, tenascin-C, and tenascin-R, in quadruple knockout mice leads to severe retinal dysfunction and diminished visual motion processing in vivo. Remarkably, impaired visual motion processing was accompanied by a developmental loss of cholinergic direction-selective starburst amacrine cells. Additionally, we noted imbalance of inhibitory and excitatory synaptic signaling in the quadruple knockout retina. Collectively, the study offers insights into the functional importance of four key extracellular matrix proteins for retinal function, visual motion processing, and synaptic signaling.
Project description:In this study, a quantitative proteomic technique based on isobaric tags for relative and absolute quantitation (iTRAQ) was used to compare the proteome of cultured sensory and motor nerve fibroblasts (Fbs). Among a total of 2597 overlapping proteins identified, we obtained 148 differentially expressed proteins, of which 116 proteins were significantly higher expressed in sensory Fbs, and 32 proteins were significantly higher expressed in motor Fbs. Western blot and qPCR analysis were applied to validate differentially expressed proteins. Functional categorization indicated that differentially expressed proteins were linked to a diverse array of biological processes , including regeneration, axon guidance, cytoskeleton organization, cell proliferation, cell migration, cell adhesion, and tissue remodeling, which might play a critical role in the specificity of peripheral nerve regeneration. Furthermore, following co-culture of motor neurons with motor or sensory Fbs , motor Fbs significantly enhanced neurite growth than sensory Fbs. These findings indicated that nerve Fbs expressed the distinct motor and sensory phenotypes involved in different patterns of protein expression, biological processes, and effects on neurons.
Project description:Peripheral nerve repair and functional recovery depend on the rate of nerve regeneration and the quality of target reinnervation. It is important to fully understand the cellular and molecular basis underlying the specificity of peripheral nerve regeneration, which means the achieving of respective correct pathfinding and accurate target reinnervation for regrowing motor and sensory axons. In this study, a quantitative proteomic technique, based on isobaric tags for relative and absolute quantitation (iTRAQ) was used to profile the protein expression pattern between single motor and sensory nerves at 14 days after peripheral nerve transection. Among a total of 1259 proteins identified, 176 proteins showed the differential expressions between injured motor and sensory nerves. Quantitative real-time RT-PCR and Western blot analysis were applied to validate the proteomic data on representative differentially expressed proteins. Functional categorization indicated that differentially expressed proteins were linked to a diverse array of molecular functions, including axonogenesis, response to axon injury, tissue remodeling, axon ensheathment, cell proliferation and adhesion, vesicle-mediated transport, response to oxidative stress, internal signal cascade, and macromolecular complex assembly, which might play an essential role in peripheral motor and sensory nerve regeneration. Overall, we hope that the proteomic database obtained in this study could serve as a solid foundation for the comprehensive investigation of differentially expressed proteins between injured motor and sensory nerves and for the mechanism elucidation of the specificity of peripheral nerve regeneration.
Project description:We performed single-cell chromatin conformation capture with our recently developed method, Dip-C, on mouse sensory neurons in visual and olfactory systems, and reconstructed their 3D genomes.
Project description:We performed micrarrays to investigate neuronal gene expression changes during acute inflammatory CNS axon injury using the murine myelin oligodendrocyte glycoprotein 35-55 (MOG35-55)-induced experimental autoimmune encephalomyelitis (EAE) model. The present study was assigned to assess the direct and indirect endogenous neuronal response to spinal axonal injury in the motor and sensory cortex. Gene expression in motor and sensory cortex enriched tissue was assessed from four healthy and six EAE female mice. Tissue was collected from mice with paraplegia or monoplegia, with contralateral hindlimb paresis (EAE day 18-21). The gene expression profiles of the EAE mice were compared to the motor or sensory cortex of healthy control mice, resulting in a list of differentially expressed genes in healthy and EAE mice.
Project description:Transcriptomic signature of the C9orf72 hexonucleotide repeat expansion in induced pluripotent stem cell derived motor and sensory neurons.
Project description:Neuronal activity-dependent transcription couples sensory experience to adaptive responses of the brain including learning and memory. Mechanisms of activity-dependent gene expression including alterations of the epigenome have been characterized. However, the fundamental question of whether and how sensory experience remodels chromatin architecture in the adult brain in vivo to induce neural code transformations and learning and memory remains to be addressed. Here, in vivo calcium imaging, optogenetics, and pharmacological approaches reveal that granule neuron activation in the anterior dorsal cerebellar vermis (ADCV) plays a crucial role in a novel delay tactile startle learning paradigm in mice. Strikingly, using large-scale transcriptome and chromatin profiling, we have discovered that activation of the motor learning-linked granule neuron circuit reorganizes neuronal chromatin including through long-distance enhancer-promoter and transcriptionally active compartment interactions to orchestrate distinct granule neuron gene expression modules. Conditional CRISPR knockout of the chromatin architecture regulator Cohesin in ADCV granule neurons in adult mice disrupts activity-dependent transcription and motor learning. These findings define how sensory experience patterns chromatin architecture and neural circuit coding in the brain to drive motor learning.
Project description:Mature cortical sensory areas are specialized to process unique sensory stimuli. Recent evidence shows that in the mouse embryo sensory cortices are prepared to respond to an incoming input from the periphery. However, whether these sensory circuits originate as modality specific modules, or they are segregated over time remains unknown. Here, we demonstrate that visual and somatosensory circuits originate as functionally intermingled modules, as whisker-pad stimulations at prenatal life led to a multimodal response activating both primary visual and somatosensory cortices. This multimodal response is switched to unimodal at birth via the superior colliculus, a midbrain structure where both modalities converge. Retinal afferent to the superior colliculus prompts the gating of visual from somatosensory circuits achieving sensory modality specificity at birth. Blocking stage I retinal waves resulted in prolonged convergence of somatosensory and visual circuits at the superior colliculus, which led to long-term consequences in the molecular identity of the superior colliculus and caused defects in eye-specific segregation and retinotopy. Hence, the superior colliculus stands as a key developmental regulator of sensory circuits by channeling modality stimuli to their appropriate sensory pathway.