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Series GSE246666 Query DataSets for GSE246666
Status Public on Nov 05, 2023
Title Selective oxytocin receptor activation prevents prefrontal circuit dysfunction and social behavioral alterations in response to chronic prefrontal cortex activation in rats
Organism Rattus norvegicus
Experiment type Expression profiling by high throughput sequencing
Summary 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.
 
Overall design Three groups of rats (N=4 for each group) with or without repeated chemogenetic activation of the PFC over 10 days and subsequent repeated treatment with an oxytocin receptor agonist or vehicle for 7 days
 
Contributor(s) Schmucki R, Janz P, Ebeling M, Grundschober C, Benekareddy M, Prasad M, Koechl F
Citation(s) 38145283
Submission date Oct 31, 2023
Last update date Jan 03, 2024
Contact name Roland Schmucki
E-mail(s) roland.schmucki@roche.com
Organization name F. Hoffmann - La Roche AG
Street address Grenzacherstrase
City Basel
ZIP/Postal code 4058
Country Switzerland
 
Platforms (1)
GPL22396 Illumina HiSeq 4000 (Rattus norvegicus)
Samples (12)
GSM7874350 mPFC, chronic PFC activation model + Vehicle treatment, rep1
GSM7874351 mPFC, chronic PFC activation model + Vehicle treatment, rep2
GSM7874352 mPFC, chronic PFC activation model + Vehicle treatment, rep3
Relations
BioProject PRJNA1034095

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Supplementary file Size Download File type/resource
GSE246666_counts.gct.gz 658.9 Kb (ftp)(http) GCT
GSE246666_rpkms.gct.gz 815.9 Kb (ftp)(http) GCT
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Raw data are available in SRA

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