Perseverative stereotypic behavior of Epac2 KO mice in a reward-based decision making task

Area of Science:

• Neuroscience
• Genetics
• Behavioral Science

Background:

• Navigating dynamic environments requires balancing staying with known options and switching to explore new ones.
• The genetic and cellular underpinnings of these "stay or switch" decisions are not well understood.
• The exchange protein directly activated by cAMP 2 (Epac2) gene is implicated as a potential autism locus.

Purpose of the Study:

• To investigate the role of Epac2 in "stay or switch" decision-making and related behaviors.
• To explore the cellular and anatomical consequences of Epac2 deletion in the brain.
• To link Epac2 function to reinforcement learning and autism-related behaviors.

Main Methods:

• Utilized a dynamic foraging task in mice to assess "stay or switch" behavior.
• Conducted anatomical analyses to quantify interneuron density in specific brain regions.
• Performed in vitro whole-cell patch-clamp recordings to examine neural activity in response to dopamine.

Main Results:

• Epac2 knockout (KO) mice exhibited perseverative "stay" behavior.
• Loss of Epac2 led to decreased density of PV-expressing interneurons in the ventrolateral orbitofrontal cortex (OFC) and dorsal striatum (dSTR).
• PV+ GABAergic interneurons in the dSTR of Epac2 KO mice showed altered activity in response to dopamine.

Conclusions:

• Epac2 plays a role in the structural and functional plasticity of PV-expressing GABAergic interneurons in the OFC and dSTR.
• These changes in interneurons may underlie abnormal decision-making and perseverative behaviors observed in Epac2 KO mice.
• Epac2 dysfunction is potentially linked to decision-making deficits and perseverative behaviors associated with autism.