Parallel anterior cingulate cortex pathways underlie dissociable social and attentional outputs.

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Systems Neuroscience

Background:

• Social behavior and attention are often impaired together in neuropsychiatric disorders like autism spectrum disorder (ASD).
• The specific neural circuits within shared brain regions that independently regulate these functions remain poorly understood.

Purpose of the Study:

• To identify distinct neuronal subpopulations in the anterior cingulate cortex (ACC) and their downstream targets.
• To investigate the differential roles of these ACC circuits in regulating social interaction and attentional control.
• To explore potential circuit-based interventions for ASD-related behavioral deficits.

Main Methods:

• Utilized optogenetics in Shank3b mutant mice, an ASD model.
• Investigated glutamatergic neuron subpopulations in the ACC projecting to the zona incerta (ZI) and the limbic sector of the thalamic reticular nucleus (lTRN).
• Assessed the impact of circuit-specific activation on social behavior and attentional allocation.

Main Results:

• Identified two distinct ACC glutamatergic neuron subpopulations projecting to ZI and lTRN.
• Demonstrated differential regulation: ACC→ZI circuit modulates social interaction, while ACC→lTRN circuit controls attentional allocation.
• Observed rescue of social deficits by activating ACC→ZI and attentional deficits by activating ACC→lTRN in Shank3b mutant mice.

Conclusions:

• Revealed dissociable ACC subpopulations and their downstream circuits governing social and attentional behaviors.
• Provides circuit-level understanding of social and attentional dysregulation in ASD models.
• Suggests potential for targeted circuit modulation to address related symptoms in psychiatric disorders.