Functional Dissociation of Anterior Cingulate Cortex Excitatory and Inhibitory Neurons in Sustained Attention and...

Cognitive control, which is essential for goal-directed behavior, depends on the anterior cingulate cortex (ACC); however, the distinct roles of excitatory and inhibitory neurons remain unclear. Combining the five-choice serial reaction time task with c-Fos staining, fiber photometry, and chemogenetics, we show that under high attentional demand, the ACC shifts from broad to selective recruitment: total c-Fos expression increases, yet the proportions of activated calcium/calmodulin-dependent protein kinase type II alpha (CaMKIIα⁺) excitatory and glutamate decarboxylase-1 (GAD1⁺) inhibitory neurons decrease. Fiber photometry reveals elevated activity in both populations during attention allocation and sensory processing, with CaMKIIα⁺ neurons contributing more prominently during decision-making. The two populations exhibit distinct activity patterns during reward anticipation and following premature responses: GAD1⁺ neurons exhibit marked increases in calcium activity, whereas CaMKIIα⁺ neurons remain essentially unchanged. Bidirectional chemogenetic manipulations demonstrate that CaMKIIα⁺ neurons mediate post-error adjustment and that GAD1⁺ neurons regulate impulsivity. These findings demonstrate that the functional dissociation between excitatory and inhibitory neurons in the ACC underpins cognitive control and may be relevant to disorders involving impaired error monitoring and impulse regulation.