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Brain motor and fear circuits differentially regulate leukocyte distribution and function during acute stress [single-cell RNA-seq]

ABSTRACT: Brain motor and fear circuits differentially regulate leukocyte distribution and function during acute stress [single-cell RNA-seq]

PROVIDER: PRJNA831430 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18906482_1.fastq.gz	Fastqsanger.gz
	SRR18906482_2.fastq.gz	Fastqsanger.gz
	SRR18906483_1.fastq.gz	Fastqsanger.gz
	SRR18906483_2.fastq.gz	Fastqsanger.gz
	SRR18906484_1.fastq.gz	Fastqsanger.gz

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Brain motor and fear circuits differentially regulate leukocyte distribution and function during acute stress

Project description:Brain motor and fear circuits differentially regulate leukocyte distribution and function during acute stress

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Brain motor and fear circuits differentially regulate leukocyte distribution and function during acute stress [bulk RNA-seq]

Project description:Brain motor and fear circuits differentially regulate leukocyte distribution and function during acute stress [bulk RNA-seq]

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Brain motor and fear circuits differentially regulate leukocyte distribution and function during acute stress [bulk RNA-seq]

Project description:The nervous and immune systems are intricately linked. Although psychological stress is known to affect immune function, direct mechanistic pathways linking stress networks in the brain to peripheral leukocytes remain poorly understood. Here, we show that distinct brain regions shape leukocyte distribution throughout the body during acute stress in mice. Using optogenetics and chemogenetics, we demonstrate that the motor cortex induces rapid neutrophil mobilization to peripheral tissues via skeletal muscle-derived neutrophil-attracting chemokines. Conversely, the paraventricular hypothalamus controls monocyte and lymphocyte egress from secondary lymphoid organs and blood to the bone marrow via direct and cell-intrinsic glucocorticoid signaling. These stress-induced counter-directional and population-wide leukocyte shifts are associated with altered disease susceptibility. On the one hand, acute stress changes innate immunity by reprogramming neutrophils and precipitating their recruitment to atherosclerotic plaques. On the other hand, stress-induced leukocyte shifts impair adaptive immunity, increasing susceptibility to SARS-Cov-2 and influenza infection but protecting against autoimmunity in a model of multiple sclerosis. Collectively, these data show that distinct brain regions differentially and rapidly tailor the leukocyte landscape during psychological stress, thus calibrating the immune system’s capacity to respond to physical threats.

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Brain motor and fear circuits differentially regulate leukocyte distribution and function during acute stress [single-cell RNA-seq]

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Brain motor and fear circuits differentially regulate leukocyte distribution and function during acute stress

Project description:This SuperSeries is composed of the SubSeries listed below.

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Functional Identification of Specialized Basal Ganglia Circuits that Regulate Vocal Motor Sequences

Project description:Production of learned vocalizations requires precise selection and accurate sequencing of appropriate vocal-motor actions. The basal ganglia are essential for the selection and sequencing of motor actions, but the cellular specializations and circuit mechanisms governing accurate sequencing of vocalizations are unknown. Here, we use single-nucleus RNA sequencing and genetic manipulations to map basal ganglia cell types and circuits involved in the production of songbird vocal sequences. We identify cell-type specializations in direct-like and indirect-like basal ganglia pathways, including evolutionary expansion of striatal and arkypallidal cell-types that could facilitate vocal sequencing. We also reversibly reduced the expression of FoxP2 with a viral knockdown. For birds in which FoxP2 was knocked down, striatal neurons exhibited decreased expression of Drd1 and showed an increased ratio of Drd2/Drd1 expression. These findings identify key evolutionary specializations and circuits essential for selection and sequencing of vocal-motor actions necessary for vocal communication.

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The gastrin-releasing peptide regulates stress-enhanced fear and dopamine signaling

Project description:Fear extinction is an adaptive behavioral process critical for organism’s survival, but deficiency in extinction may lead to PTSD. While the amygdala and its neural circuits are critical for fear extinction, the molecular identity and organizational logic of cell types that lie at the core of these circuits remain unclear. Here we report that mice deficient for amygdala-enriched gastrin-releasing peptide gene (Grp-/-) exhibit enhanced neuronal activity in the basolateral amygdala (BLA) and stronger fear conditioning, as well as deficient extinction in stress-enhanced fear learning (SEFL). rAAV2-retro-based tracing combined with visualization of the GFP knocked in the Grp gene showed that BLA receives several GRPergic conditioned stimulus projections: from the indirect auditory thalamus-to-auditory cortex pathway, medial prefrontal cortex, ventral hippocampus and ventral tegmental area. Transcription of dopamine-related genes was decreased in BLA of Grp-/- mice following SEFL extinction recall, suggesting that the GRP may mediate fear extinction regulation by dopamine.

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Sex-Specific Astrocyte Regulation of Spinal Motor Circuits by Nkx6.1 [RNA-seq]

Project description:Sex-Specific Astrocyte Regulation of Spinal Motor Circuits by Nkx6.1 [RNA-seq]

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Functional Identification of Specialized Basal Ganglia Circuits that Regulate Vocal Motor Sequences

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