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Molecular Neurobiology of Loss

ABSTRACT: Molecular Neurobiology of Loss

PROVIDER: PRJNA858028 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20096904_1.fastq.gz	Fastqsanger.gz
	SRR20096904_2.fastq.gz	Fastqsanger.gz
	SRR20096905_1.fastq.gz	Fastqsanger.gz
	SRR20096905_2.fastq.gz	Fastqsanger.gz
	SRR20096906_1.fastq.gz	Fastqsanger.gz

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Molecular Neurobiology of Loss Part 1

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Molecular Neurobiology of Loss Part 1

Project description:Psychological loss is a common experience that erodes well-being and negatively impacts quality of life. The molecular underpinnings of loss are poorly understood, making it challenging to develop treatment strategies. Here, we investigate the mechanisms of loss using an enrichment removal (ER) paradigm in rats. RNA-seq was used to investigate the molecular landscape of the basolateral amygdala (BLA), a region previously implicated in loss, in adult male Sprague-Dawley rats following ER. Rats were subjected to standard housing (SH) for 6 weeks, environmental enrichment (EE) for 6 weeks, or enrichment removal (ER), consisting of 4 weeks of EE followed by 2 weeks of removal into impoverished conditions (n=6/group). Rats were then perfused and micropunches were collected from the basolateral amygdala (BLA) for bulk RNA-seq.

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Molecular Neurobiology of Loss

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Molecular neurobiology of loss: a role for basolateral amygdala extracellular matrix.

Project description:Psychological loss is a common experience that erodes well-being and negatively impacts quality of life. The molecular underpinnings of loss are poorly understood. Here, we investigate the mechanisms of loss using an environmental enrichment removal (ER) paradigm in male rats. The basolateral amygdala (BLA) was identified as a region of interest, demonstrating differential Fos responsivity to ER and having an established role in stress processing and adaptation. A comprehensive multi-omics investigation of the BLA, spanning multiple cohorts, platforms, and analyses, revealed alterations in microglia and the extracellular matrix (ECM). Follow-up studies indicated that ER decreased microglia size, complexity, and phagocytosis, suggesting reduced immune surveillance. Loss also substantially increased ECM coverage, specifically targeting perineuronal nets surrounding parvalbumin interneurons, suggesting decreased plasticity and increased inhibition within the BLA following loss. Behavioral analyses suggest that these molecular effects are linked to impaired BLA salience evaluation, leading to a mismatch between stimulus and reaction intensity. These loss-like behaviors could be rescued by depleting BLA ECM during the removal period, helping us understand the mechanisms underlying loss and revealing novel molecular targets to ameliorate its impact.

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