Layer-specific pyramidal neuron properties underlie diverse anterior cingulate cortical motor and limbic networks

The laminar cellular and circuit mechanisms by which the anterior cingulate cortex (ACC) exerts flexible control of motor and affective information for goal-directed behavior have not been elucidated. Using multimodal tract-tracing, in vitro patch-clamp recording and computational approaches in rhesus monkeys (M. mulatta), we provide evidence that specialized motor and affective network dynamics can be conferred by layer-specific biophysical and structural properties of ACC pyramidal neurons targeting two key downstream structures - the dorsal premotor cortex (PMd) and the amygdala (AMY). AMY-targeting neurons exhibited significant laminar differences, with L5 more excitable (higher input resistance and action potential firing rates) than L3 neurons. Between-pathway differences were found within L5, with AMY-targeting neurons exhibiting greater excitability, apical dendritic complexity, spine densities, and diversity of inhibitory inputs than PMd-targeting neurons. Simulations using a pyramidal-interneuron network model predict that these layer- and pathway-specific single-cell differences contribute to distinct network oscillatory dynamics. L5 AMY-targeting networks are more tuned to slow oscillations well-suited for affective and contextual processing timescales, while PMd-targeting networks showed strong beta/gamma synchrony implicated in rapid sensorimotor processing. These findings are fundamental to our broad understanding of how layer-specific cellular and circuit properties can drive diverse laminar activity found in flexible behavior.