Specific synapses develop preferentially among sister excitatory neurons in the neocortex

Abstract

The neocortex functions as the executive control centre of the brain in mammals, contributing critically to perception and behaviour. Its structure is complex yet highly organized, though the factors regulating cortical microcircuitry wiring relationships remain poorly understood. A new study in mouse embryos reveals that neurons originating from the same progenitor cell (ontogenetic radial clones) within the developing neocortex are more likely to be synaptically connected to each other than to non-sibling neurons, resulting in the formation of functional columnar microstructures with single-cell resolution. This study reveals that cells originating from the same mother cell (ontogenetic radial clones) were more likely to be connected to each other within the developing neocortex. These specific microcircuits may underlie or contribute to the establishment of interconnected local neuronal ensembles that define functional cortical columns. Neurons in the mammalian neocortex are organized into functional columns1,2. Within a column, highly specific synaptic connections are formed to ensure that similar physiological properties are shared by neuron ensembles spanning from the pia to the white matter. Recent studies indicate that synaptic connectivity in the neocortex is sparse and highly specific3,4,5,6,7,8 to allow even adjacent neurons to convey information independently9,10,11,12. How this fine-scale microcircuit is constructed to create a functional columnar architecture at the level of individual neurons largely remains a mystery. Here we investigate whether radial clones of excitatory neurons arising from the same mother cell in the developing neocortex serve as a substrate for the formation of this highly specific microcircuit. We labelled ontogenetic radial clones of excitatory neurons in the mouse neocortex by in utero intraventricular injection of enhanced green fluorescent protein (EGFP)-expressing retroviruses around the onset of the peak phase of neocortical neurogenesis. Multiple-electrode whole-cell recordings were performed to probe synapse formation among these EGFP-labelled sister excitatory neurons in radial clones and the adjacent non-siblings during postnatal stages. We found that radially aligned sister excitatory neurons have a propensity for developing unidirectional chemical synapses with each other rather than with neighbouring non-siblings. Moreover, these synaptic connections display the same interlaminar directional preference as those observed in the mature neocortex. These results indicate that specific microcircuits develop preferentially within ontogenetic radial clones of excitatory neurons in the developing neocortex and contribute to the emergence of functional columnar microarchitectures in the mature neocortex.