Precise Long-Range Microcircuit-to-Microcircuit Communication Connects the Frontal and Sensory Cortices in the Mammalian Brain

The frontal area of the cerebral cortex provides long-range inputs to sensory areas to modulate neuronal activity and information processing. These long-range circuits are crucial for accurate sensory perception and complex behavioral control; however, little is known about their precise circuit organization. Here we specifically identified the presynaptic input neurons to individual excitatory neuron clones as a unit that constitutes functional microcircuits in the mouse sensory cortex. Interestingly, the long-range input neurons in the frontal but not contralateral sensory area are spatially organized into discrete vertical clusters and preferentially form synapses with each other over nearby non-input neurons. Moreover, the assembly of distant presynaptic microcircuits in the frontal area depends on the selective synaptic communication of excitatory neuron clones in the sensory area that provide inputs to the frontal area. These findings suggest that highly precise long-range reciprocal microcircuit-to-microcircuit communication mediates frontal-sensory area interactions in the mammalian cortex. [Display omitted] •Sensory excitatory neuron clones receive defined long-range presynaptic inputs•Presynaptic neurons in frontal area are organized into discrete radial clusters•Presynaptic neurons in frontal area selectively form synapses with each other•Reciprocal microcircuit communication connects frontal and sensory cortices Ren et al. identify presynaptic neurons innervating individual excitatory neuron clones that constitute microcircuits in the sensory cortex and reveal that input neurons in the frontal cortex are organized in discrete vertical clusters and preferentially form synapses with each other.