ARNT2 controls prefrontal somatostatin interneurons mediating affective empathy

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Empathy is vital for social interaction but is often impaired in neuropsychiatric conditions.
• The genetic and neural bases of empathy variations are not well understood.

Purpose of the Study:

• To investigate the genetic and neural mechanisms underlying empathy variability.
• To identify key molecular drivers of affective empathy.

Main Methods:

• Forward genetic mapping
• Transcriptome analysis
• Selective gene ablation in mice
• Electrophysiological recordings in the anterior cingulate cortex (ACC)

Main Results:

• Aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) was identified as a crucial gene for observational fear (affective empathy).
• ARNT2 disruption in the ACC reduced affect sharing and vicarious freezing in mice.
• ARNT2 ablation in somatostatin (SST)-expressing interneurons altered neuronal excitability and brain oscillations in the ACC.
• ARNT2-expressing SST interneurons were found to regulate affective state discrimination.

Conclusions:

• ARNT2 plays a significant role in modulating affective empathy and social behavior.
• Dysfunction in ARNT2-expressing neurons in the ACC may underlie social-affective deficits in psychiatric disorders.
• ARNT2 polymorphisms may be linked to human emotion recognition deficits.