Selective Vulnerability of Parvocellular Oxytocin Neuron in Social Dysfunction
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1028986 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26409608_1.fastq.gz | Fastqsanger.gz | |||
| SRR26409608_2.fastq.gz | Fastqsanger.gz | |||
| SRR26409609_1.fastq.gz | Fastqsanger.gz | |||
| SRR26409609_2.fastq.gz | Fastqsanger.gz | |||
| SRR26409610_1.fastq.gz | Fastqsanger.gz |
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Project description:Despite the rapid progress in dissecting neural circuits for social behaviors, it remains unknown whether specific neural cell types are selectively vulnerable in social dysfunction cases often associated with neurodevelopmental disorders. Here, employing a single-cell transcriptome analysis in mice, we show that an embryonic disturbance known to induce social dysfunction preferentially impairs gene expressions crucial for neural functions in parvocellular oxytocin (OT) neurons—a subtype linked to social rewards—while neighboring cell types experience a lesser impact. Chemogenetic stimulation of OT neurons at the neonatal stage ameliorated social deficits, concomitant with a cell-type-specific sustained recovery of the pivotal gene expressions. Our data illuminates the transcriptomic selective vulnerability within the hypothalamic social behavioral center, offering a potential therapeutic target through specific neonatal neurostimulation.
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Project description:Social behavioral changes are a hallmark of several neurodevelopmental and neuropsychiatric conditions, nevertheless the underlying neural substrates of such dysfunction remain poorly understood. Building evidence points to the prefrontal cortex (PFC) as one of the key brain regions that orchestrates social behavior. We used this concept with the aim to develop a translational rat model of social-circuit dysfunction, the chronic PFC activation model (CPA). Chemogenetic designer receptor hM3Dq was used to induce chronic activation of the PFC over 10 days, and the behavioral and electrophysiological signatures of prolonged PFC hyperactivity were evaluated. To test the sensitivity of this model to pharmacological interventions on longer timescales, and validate its translational potential, the rats were treated with our novel highly selective oxytocin receptor (OXTR) agonist RO6958375, which is not activating the related vasopressin V1a receptor. CPA rats showed reduced sociability in the three-chamber sociability test, and a concomitant decrease in neuronal excitability and synaptic transmission within the PFC as measured by electrophysiological recordings in acute slice preparation. Sub-chronic treatment with a low dose of the novel OXTR agonist following CPA interferes with the emergence of PFC circuit dysfunction, abnormal social behavior and specific transcriptomic changes. These results demonstrate that sustained PFC hyperactivity modifies circuit characteristics and social behaviors in ways that can be modulated by selective OXTR activation and that this model may be used to understand the circuit recruitment of prosocial therapies in drug discovery.
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