Scientific Understanding of Consciousness
Consciousness as an Emergent Property of Thalamocortical Activity

Functional Columnar Architecture Formation in Neocortex

 

Nature 458, 501-504 (26 March 2009)

Specific synapses develop preferentially among sister excitatory neurons in the neocortex

Yong-Chun Yu¹, Ronald S. Bultje^1,2, Xiaoqun Wang¹ & Song-Hai Shi¹

Developmental Biology Program, Memorial Sloan Kettering Cancer Centre, 1275 York Avenue

Department of Pharmacology, Weill Medical College of Cornell University, 445 East 69th Street, New York, New York 10065, USA

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Neurons in the mammalian neocortex are organized into functional columns. 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 specific to allow even adjacent neurons to convey information independently. 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.

Recent studies have demonstrated that radial glial cells are the major neuronal progenitors in the developing neocortex. In addition to their well-characterized role in guiding the radial migration of post-mitotic neurons, radial glial cells divide asymmetrically to self-renew and give rise to neurons. Consecutive asymmetric cell divisions of individual radial glial cells produce several clonally related neurons that migrate radially into the cortical plate. This results in a columnar arrangement of neocortical neurons—the ontogenetic radial clone. It has previously been suggested that ontogenetic columns become the basic processing unit in the adult cortex.

The concept of the column has cast a dominant influence on our understanding of the functional organization of the neocortex. From its inception, the concept of the functional column has been considered on both a macroscopic and microscopic scale. However, most of our knowledge about functional columns and neocortical maps comes from measurements with limited spatial resolution. Recent in vivo Ca²⁺ imaging studies elegantly demonstrated that even adjacent neurons can have distinct physiological properties, indicating that neocortical maps are built with single-neuron precision. In this study, we found that sister excitatory neurons in individual radial clones in the developing mouse neocortex preferentially develop highly specific synaptic connections with each other, creating radial columnar microarchitectures of interconnected neuron ensembles with single-neuron resolution. The high degree of similarity in the direction of interlaminar connectivity between the synapses formed within individual ontogenetic radial clones and those observed in the mature neocortex suggests that these radial clones contribute to the formation of precise functional columnar architectures in the neocortex.

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