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Astrocyte-derived thrombospondins 1 and 2 are required for cortical synapse development controlling goal-directed action performance.

ABSTRACT: Astrocyte-derived thrombospondins 1 and 2 are required for cortical synapse development controlling goal-directed action performance.

PROVIDER: PRJNA1080221 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28087248_1.fastq.gz	Fastqsanger.gz
	SRR28087248_2.fastq.gz	Fastqsanger.gz
	SRR28087249_1.fastq.gz	Fastqsanger.gz
	SRR28087249_2.fastq.gz	Fastqsanger.gz
	SRR28087250_1.fastq.gz	Fastqsanger.gz

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Astrocyte-derived thrombospondins 1 and 2 are required for cortical synapse development controlling goal-directed action performance.

Project description:During development, controlled synaptogenesis is required to form functioning neural circuits that underlie cognition and behavior. Astrocytes, a major glial-cell type in the central nervous system (CNS), promote synapse formation by secreting synaptogenic proteins. Thrombospondins 1 and 2 (TSP1/2), which act through their neuronal receptor α2δ-1, are required for proper intracortical excitatory synaptogenesis. In the adult brain, the loss of α2δ-1 impairs training-induced excitatory synaptogenesis in the anterior cingulate cortex (ACC), and this impairment leads to increased effort-exertion during high-effort tasks. Here, we tested whether TSP1 and TSP2 are required for controlling effort during operant conditioning by using a lever press for food reward training in mice. Surprisingly, we found that constitutive loss of TSP1/2 significantly reduced lever pressing performance when the effort required for a food reward was increased, a phenotype opposite of α2δ-1 loss. Loss of TSP1/2 reduced excitatory synapse number significantly in adult brains. However, in the ACC of TSP1/2 knockout mice, there was still training-induced excitatory synaptogenesis, likely through the upregulation of TSP4, a TSP isoform that is also synaptogenic. Unexpectedly, we also found a significant increase in inhibitory synapse number and function in the ACC of TSP1/2 knockout mice, which were eliminated after training. Finally, we found that astrocyte-specific ablation of TSP1/2 in developing but not adult astrocytes is sufficient to reduce performance during high-effort tasks. Taken together, our study highlights the importance of developmental astrocyte-derived synaptogenic cues TSP1 and 2 in establishing excitatory and inhibitory circuits that control effort during operant conditioning in adults.

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Astrocyte-derived Interleukin-33 promotes microglial synapse engulfment and neural circuit development

Project description:Astrocyte-derived Interleukin-33 promotes microglial synapse engulfment and neural circuit development

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Astrocyte-derived Interleukin-33 promotes microglial synapse engulfment and neural circuit development I

Project description:Astrocyte-derived Interleukin-33 promotes microglial synapse engulfment and neural circuit development I

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Astrocyte-derived Interleukin-33 promotes microglial synapse engulfment and neural circuit development II

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Astrocyte developmental transcriptome from mouse visual cortex

Project description:Analysis of astrocyte gene expression across postnatal development in the mouse visual cortex, spanning the time of synaptogenesis and synapse maturation.

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Astrocyte-encoded positional cues maintain sensorimotor circuit integrity

Project description:Astrocytes, the most abundant cells in the central nervous system, promote synapse formation and help refine neural connectivity. Although they are allocated to spatially distinct regional domains during development, it is unknown whether region-restricted astrocytes are functionally heterogeneous. Here we show that postnatal spinal cord astrocytes express several region-specific genes, and that ventral astrocyte-encoded Semaphorin3a (Sema3a) is required for proper motor neuron and sensory neuron circuit organization. Loss of astrocyte-encoded Sema3a led to dysregulated α−motor neuron axon initial segment orientation, markedly abnormal synaptic inputs, and selective death of α−but not of adjacent γ−motor neurons. Additionally, a subset of TrkA+ sensory afferents projected to ectopic ventral positions. These findings demonstrate that stable maintenance of a positional cue by developing astrocytes influences multiple aspects of sensorimotor circuit formation. More generally, they suggest that regional astrocyte heterogeneity may help to coordinate postnatal neural circuit refinement. 12 total samples consisting of three biological replicates each of flow sorted postnatal day 7 dorsal spinal cord astrocytes, ventral spinal cord astrocytes, dorsal SC non astrocytes, and ventral SC non astrocytes

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Astrocyte-derived Interleukin-33 promotes microglial synapse engulfment and neural circuit development II

Project description:Neuronal synapse formation and remodeling is essential to central nervous system (CNS) development and is dysfunctional in neurodevelopmental diseases. Innate immune signals regulate tissue remodeling in the periphery, but how this impacts CNS synapses is largely unknown. Here we show that the IL-1 family cytokine Interleukin-33 (IL-33) is produced by developing astrocytes and is developmentally required for normal synapse numbers and neural circuit function in the spinal cord and thalamus. We find that IL-33 signals primarily to microglia under physiologic conditions, that it promotes microglial synapse engulfment, and that it can drive microglial-dependent synapse depletion in vivo. These data reveal a cytokine-mediated mechanism required to maintain synapse homeostasis during CNS development.

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Astrocyte-derived Interleukin-33 promotes microglial synapse engulfment and neural circuit development I

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Astrocyte morphogenesis is dependent on BDNF signaling via astrocytic TrkB.T1

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2019-08-26 | GSE122176 | GEO

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Project description:Astrocytes, a major cell type found throughout the central nervous system, have general roles in the modulation of synapse formation and synaptic transmission, blood-brain-barrier formation and regulation of blood flow, as well as metabolic support of other brain resident cells. To investigate the true extent of astrocyte molecular diversity across forebrain regions, we used single cell RNA sequencing and generated a database containing ~2000 astrocytes. Our analysis identifies five transcriptomically distinct astrocyte subtypes in adult mouse cortex and hippocampus. Validation of our data in situ reveals distinct spatial positioning of defined subtypes, reflecting the distribution of morphologically and physiologically distinct astrocyte populations. Our findings are evidence for specialized astrocyte subtypes between and within brain regions.

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