A developmental switch in corticoclaustral signaling

The anterior cingulate cortex (ACC) is a high-order cortical region involved in different functions including attention,^1,2 pain processing,^3,4,5 and predictive coding.^6,7,8,9 ACC neurons send top-down inputs to several cortical and subcortical brain regions including the claustrum.^{10,11,12,13,14,15} Synaptic input from the ACC is thought to drive the activation of claustrum neurons, which in turn amplify and distribute ACC-related information back to the cortex to help orchestrate cortical networks during demanding cognitive states.^12,16,17,18 However, the circuit mechanisms underlying ACC-claustrum signaling have mainly been investigated during adulthood and in vitro. Using in vivo electrophysiological recordings, we determined how ACC inputs modulated excitatory and inhibitory claustrum neurons through early development and adulthood. We show that ACC activation strongly excites claustral fast-spiking inhibitory neurons, which leads to feedforward inhibition of claustrum neurons in adult mice. This feedforward inhibition is reduced by chemogenetic suppression of claustral parvalbumin interneurons. However, during early postnatal development, ACC inputs evoke stronger excitatory currents, slower inhibitory currents, and feedforward excitation of claustrum circuits. The switch from ACC-claustrum excitation to inhibition during development correlates with the emergence of claustrum parvalbumin neurons in the third postnatal week. Therefore, during adulthood, the ACC has a predominantly inhibitory effect on the claustrum, which may serve to prevent claustrum interference with top-down ACC communication to other cortical targets. However, during early phases of forebrain development, ACC excitatory drive of the claustrum may promote the establishment of mature connectivity between these regions.