Sex-specific impact of the NPS system on top-down control of fear behavior in mice

• Applicant: Privatdozent Dr. Kay Jüngling
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; Experimental Models for the Understanding of Nervous System Diseases ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 499442527

The life time prevalence for the development of anxiety or panic disorders is two to three times higher in women compared to men. Human and rodent research provides evidence that there are sex-specific differences in emotion regulation i.e. in fear extinction. In female rodents, attenuated fear extinction is regularly observed following classical fear conditioning. Recent data implicate an influence of the neuropeptide S system on fear extinction in a sex-dependent manner, where the functional polymorphisms of the neuropeptide S receptor (NPSR1) shape the time course of extinction predominantly in female mice. Although the amygdala has been identified as a crucial structure mediating these effects, nothing is known about the function of the NPS system in other highly fear-relevant circuits, which are known to mediate top-down control of emotion regulation, i.e. the medial prefrontal cortex (mPFC) and connected subcortical structures. Here we aim to analyze 1) the electrophysiological properties of NPSR1-expressing neurons in the prelimbic region (PL) of the mPFC and their synaptic connections to subcortical (i.e. amygdala) regions, 2) identify their activation profile during fear memory retrieval and extinction using specific temporal and spatial distribution of immediate early gene mRNA, and 3) test their contribution to fear extinction via pathway-specific chemogenetic manipulation. We will compare these parameters between male and female mice of a novel transgenic NPSR1-Cre mouse line. Thereby, the project will contribute to the understanding of sex-specific differences in emotion regulation.

• DFG Programme: Research Grants