The anterior cingulate cortex drives lateralized age-dependent modulation of claustrum circuits

The anterior cingulate cortex (ACC) sends top-down inputs to the claustrum during sensory, motor, and cognitive processing. This ACC input is thought to drive the activation of claustrum neurons which in turn project back to the cortex to help orchestrate cortical networks during demanding cognitive states such as attention. However, the circuit mechanisms underlying ACC-claustrum signaling are not fully understood. Using in vivo single neuron recordings in mice, we show that ACC neuron activation drives a lateralized modulation of claustrum excitability that changes as a function of postnatal age. In adulthood, ACC activation evoked feed-forward inhibition of ipsilateral excitatory claustrum neurons and activation of contralateral excitatory claustrum neurons. Chemogenetic manipulation in adult mice revealed that ipsilateral claustrum inhibition by the ACC was due to feed-forward activation of claustrum parvalbumin inhibitory neurons. However, in neonatal mice, which lack mature parvalbumin interneurons, ACC inputs evoked claustrum excitation. In juvenile mice, the developmental switch from ACC-evoked claustrum excitation to inhibition occurred in parallel with the maturation of claustrum parvalbumin interneurons, thus corroborating the chemogenetic findings. Therefore, this work provides a novel mechanism of cortical control over claustrum activity that is refined during early postnatal life.