Specific synapses develop preferentially among sister excitatory neurons in the neocortex

Abstract

Neurons in the mammalian neocortex are organized into functional columns 1, 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 suggest that synaptic connectivity in the neocortex is sparse and highly specific 3–8 to allow even adjacent neurons to convey information independently 9–12. 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 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 suggest 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.

Gradients in the Brain: The Control of the Development of Form and Function in the Cerebral Cortex

“…An attractive theory has been that the mini or microcolumns of highly connected neurons in the adult are groups of clonally related neurons. In support of this, it has recently been reported that radially aligned, clonally related neurons preferentially connect to one another, suggesting that ontogenic units/radial clones may be a component of functional microcolumns (Yu et al 2009). If this observation generalizes to different parts of the cortex, it would provide a potentially powerful framework for integrating spatial patterning of the cortex with the formation of vertically arranged, area-specific circuits within cortical columns.…”

“…(C) Cortical stem cells generate radially arranged clones of neurons in mice and primates. Examples of retrovirally labeled clones are redrawn from Kornack andRakic 1995 andYu et al 2009. extend through the cortical plate. In contrast, the protomap hypothesis proposed that neocortical areas were patterned from a map of spatial identity intrinsic to neocortical stem cells (Rakic 1988a).…”

Direction-selective retinal ganglion cells arise from molecularly specified multipotential progenitors

“…In the cortex, clonal relatives are often synaptic partners (37). In the retina, starburst amacrine cells provide a major input to ooDSGCs, but to few other RGC subtypes (5, 31).…”

Spatial representation in the hippocampal formation: a history

“…Excitatory neurons from the same radial glial progenitor are known to have stronger interconnections than other cells 266,267 . Might such connectivity between clonally related cells underlie a possible preferential coupling between MEC cells with similar spatial or directional tuning, in the same way that cells from the same clone exhibit similarities in orientation preferences (and possibly preferential coupling) in the visual cortex 268,269 ?…”