Functional optic tract rewiring via subtype- and target-specific axonal regeneration and presynaptic activity enhancement
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ABSTRACT:
PROVIDER: PRJNA1113667 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29089800_1.fastq.gz | Fastqsanger.gz | |||
| SRR29089800_2.fastq.gz | Fastqsanger.gz | |||
| SRR29090200_1.fastq.gz | Fastqsanger.gz | |||
| SRR29090200_2.fastq.gz | Fastqsanger.gz | |||
| SRR29090300_1.fastq.gz | Fastqsanger.gz |
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Project description:Mechanisms underlying functional axonal rewiring after adult mammalian central nervous system (CNS) injuries remain unclear partially due to limited models. Using a mouse intracranial pre–olivary pretectal nucleus (OPN) optic tract injury model, we demonstrate that Pten/Socs3 knockout and CNTF expression in retinal ganglion cells (RGCs) promotes optic tract regeneration and reinnervation into OPN. Revealed by transmission electron microscopy, trans-synaptic labeling and electrophysiology, functional synapses are formed in OPN mainly by intrinsically photosensitive RGCs, thereby partially restoring the pupillary light reflex (PLR). Furthermore, combining with Lipin-1 knockdown accelerates the recovery and achieves functional reconnection in the chronic injury paradigm. PLR can be further boosted by increasing either RGC photosensitivity with melanopsin or optic tract presynaptic release with a voltage-gated calcium channel modulator, the latter of which also improves corticospinal-tract-sprouting-induced functional recovery after stroke. These findings highlight the importance of neuronal types and presynaptic activity for functional reconnection after CNS injuries.
2025-01-23 | GSE267935 | GEO
Project description:Mechanisms underlying functional axonal rewiring after adult mammalian central nervous system (CNS) injuries remain unclear partially due to limited models. Using a mouse intracranial pre–olivary pretectal nucleus (OPN) optic tract injury model, we demonstrate that Pten/Socs3 knockout and CNTF expression in retinal ganglion cells (RGCs) promotes optic tract regeneration and reinnervation into OPN. Revealed by transmission electron microscopy, trans-synaptic labeling and electrophysiology, functional synapses are formed in OPN mainly by intrinsically photosensitive RGCs, thereby partially restoring the pupillary light reflex (PLR). Furthermore, combining with Lipin-1 knockdown accelerates the recovery and achieves functional reconnection in the chronic injury paradigm. PLR can be further boosted by increasing either RGC photosensitivity with melanopsin or optic tract presynaptic release with a voltage-gated calcium channel modulator, the latter of which also improves corticospinal-tract-sprouting-induced functional recovery after stroke. These findings highlight the importance of neuronal types and presynaptic activity for functional reconnection after CNS injuries.
2025-01-23 | GSE267936 | GEO
Project description:Functional Optic Tract Rewiring via Subtype- and Target-specific Axonal Regeneration and Presynaptic Activity Enhancement (scRNA-Seq)
| PRJNA1113669 | ENA
Project description:Functional Optic Tract Rewiring via Subtype- and Target-specific Axonal Regeneration and Presynaptic Activity Enhancement (bulk RNA-Seq)
| PRJNA1113670 | ENA
Project description:Mechanisms underlying functional axonal rewiring after adult mammalian central nervous system (CNS) injuries remain unclear partially due to limited models. Here we develop a mouse intracranial pre-olivary pretectal nucleus (OPN) optic tract injury model and demonstrate that Pten/Socs3 knockout and CNTF expression in retinal ganglion cells (RGCs) promotes optic tract regeneration and OPN reinnervation. Revealed by transmission electron microscopy, trans-synaptic labeling, and electrophysiology, functional synapses are formed in OPN mainly by intrinsically photosensitive RGCs, thereby partially restoring the pupillary light reflex (PLR). Moreover, combining with Lipin1 knockdown accelerates the recovery and achieves functional reconnection after chronic injury. PLR can be further boosted by increasing RGC photosensitivity with melanopsin overexpression, and it can also be enhanced by treatment of a voltage-gated calcium channel modulator to augment presynaptic release. These findings highlight the importance of neuronal types and presynaptic activity for functional reconnection after CNS injuries.
| S-EPMC11880380 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-01-23 | GSE267938 | GEO
Project description:We used optic nerve injury as a model to study early signaling events in the neuronal soma following axonal injury. Optic nerve injury results in the selective death of retinal ganglion cells (RGCs). The time course of cell death takes place over a period of days with the earliest detection of RGC death at about 48 hr post injury. We hypothesized that in the period immediately following axonal injury, there are changes in the soma that signal surrounding glia and neurons and that start programmed cell death. In the current study, we investigated early changes in cellular signaling and gene expression that occur within the first 6 hrs post optic nerve injury. We detected differences in phosphoproteins and gene expression within this time period that we used to interpret temporal events. Our studies revealed that the entire retina has been signaled by the RGC soma within 30 min after optic nerve injury and that pathways that modulate cell death are likely to be active in RGCs within 6 hrs following axonal injury Experiment Overall Design: In the treated animals, axons of the optic nerve were crushed with fine forceps for 10 sec, 1 mm posterior to the globe, under direct visualization, within an intact meningeal sheath. Controls were contralateral eyes from the same animals in each group that had not been injured. After 6 hr eyes were enucleated and processed for tissue sectionin
2008-10-25 | E-GEOD-11862 | biostudies-arrayexpress
Project description:Background Local translation at synapses is important for rapidly remodeling the synaptic proteome to sustain long-term plasticity and memory. While the regulatory mechanisms underlying memory-associated local translation have been widely elucidated in the postsynaptic/dendritic region, there is no direct evidence for which RNA-binding protein (RBP) in axons controls target-specific mRNA translation to promote long-term potentiation (LTP) and memory. We previously reported that translation controlled by cytoplasmic polyadenylation element binding protein 2 (CPEB2) is important for postsynaptic plasticity and memory. Here, we investigated whether CPEB2 regulates axonal translation to support presynaptic plasticity. Methods Behavioral and electrophysiological assessments were conducted in mice with pan neuron/glia- or AQ2glutamatergic neuron-specific knockout of CPEB2. Hippocampal Schaffer collateral (SC)-CA1 and temporoammonic (TA)-CA1 pathways were electro-recorded to monitor synaptic transmission and LTP evoked by 4 trains of high-frequency stimulation. RNA immunoprecipitation, coupled with bioinformatics analysis, were used to unveil CPEB2-binding axonal RNA candidates associated with learning, which were further validated by Western blotting and luciferase reporter assays. Adeno-associated viruses expressing Cre recombinase were stereotaxically delivered to the pre- or post-synaptic region of the TA circuit to ablate Cpeb2 for further electrophysiological investigation. Biochemically isolated synaptosomes and axotomized neurons cultured on a microfluidic platform were applied to measure axonal protein synthesis and FM4-64FX-loaded synaptic vesicles. Results Electrophysiological analysis of hippocampal CA1 neurons detected abnormal excitability and vesicle release probability in CPEB2-depleted SC and TA afferents, so we cross-compared the CPEB2-immunoprecipitated transcriptome with a learning-induced axonal translatome in the adult cortex to identify axonal targets possibly regulated by CPEB2. We validated that Slc17a6, encoding vesicular glutamate transporter 2 (VGLUT2), is translationally upregulated by CPEB2. Conditional knockout of CPEB2 in VGLUT2-expressing glutamatergic neurons impaired consolidation of hippocampus-dependent memory in mice. Presynaptic-specific ablation of Cpeb2 in VGLUT2-dominated TA afferents was sufficient to attenuate protein synthesis-dependent LTP. Moreover, blocking activity-induced axonal Slc17a6 translation by CPEB2 deficiency or cycloheximide diminished the releasable pool of VGLUT2-containing synaptic vesicles. Conclusions We identified 272 CPEB2-binding transcripts with altered axonal translation post-learning and established a causal link between CPEB2-driven axonal synthesis of VGLUT2 and presynaptic translation-dependent LTP. These findings extend our understanding of memory-related translational control mechanisms in the presynaptic compartment.
2024-07-08 | GSE208738 | GEO
Project description:Despite considerable evidence that RNA-binding proteins (RBPs) regulate mRNA transport and local translation in dendrites, roles for axonal RBPs are poorly understood. Here we demonstrate that a nontelomeric isoform of telomere repeat-binding factor 2 (TRF2-S) is a novel RBP that regulates axonal plasticity. TRF2-S interacts directly with target mRNAs to facilitate their axonal delivery. The process is antagonized by fragile X mental retardation protein (FMRP). Distinct from the current RNA-binding model of FMRP, we show that FMRP occupies the GAR domain of TRF2-S protein to block the assembly of TRF2-S-mRNA complexes. Overexpressing TRF2-S and silencing FMRP promotes mRNA entry to axons, and enhances axonal outgrowth and neurotransmitter release from presynaptic terminals. Our findings suggest a pivotal role for TRF2-S in an axonal mRNA localization pathway that enhances axon outgrowth and neurotransmitter release.
2015-11-06 | GSE72887 | GEO
Project description:Despite considerable evidence that RNA-binding proteins (RBPs) regulate mRNA transport and local translation in dendrites, roles for axonal RBPs are poorly understood. Here we demonstrate that a nontelomeric isoform of telomere repeat-binding factor 2 (TRF2-S) is a novel RBP that regulates axonal plasticity. TRF2-S interacts directly with target mRNAs to facilitate their axonal delivery. The process is antagonized by fragile X mental retardation protein (FMRP). Distinct from the current RNA-binding model of FMRP, we show that FMRP occupies the GAR domain of TRF2-S protein to block the assembly of TRF2-S-mRNA complexes. Overexpressing TRF2-S and silencing FMRP promotes mRNA entry to axons, and enhances axonal outgrowth and neurotransmitter release from presynaptic terminals. Our findings suggest a pivotal role for TRF2-S in an axonal mRNA localization pathway that enhances axon outgrowth and neurotransmitter release. RNA immunoprecipitated samples using either anti-rat TRF2-S or rabbit IgG antibodies were used to generate biotin-labeled RNA using the Illumina Total Prep RNA Amplification Kit (Ambion), which was hybridized to Illumina's rat Ref-12 Expression BeadChips (Illumina, San Diego, CA), containing 22,523 well-annotated RefSeq transcripts with ~30-fold redundancy. The arrays were scanned using an Illumina BeadStation 500X Genetic Analysis Systems scanner and the image data extracted using Illumina BeadStudio software, version 1.5, normalized by Z-score transformation and used to calculate differences in signal intensities. Significant values were calculated from two groups of independent experiments, using a two-tailed Z-test with P < 0.05, a false discovery rate <0.30, a z ratio absolute value not less than 1.5, and an average signal intensity not less than zero. The results also had to pass the filtering and one-way independent ANOVA test by sample groups less than 0.05, and detection p-value for any probe in the comparison group less than 0.02.
2015-11-06 | E-GEOD-72887 | biostudies-arrayexpress