Laminar and Columnar Development of Barrel Cortex Relies on Thalamocortical Neurotransmission

A dynamic interplay between intrinsic regional molecular cues and extrinsic factors from the thalamus shape multiple features of early cortical development. It remains uncertain and controversial, however, whether the initial formation of cortical columns depends on neuronal activity, and there is little evidence that cortical lamination or neuronal differentiation is influenced by extrinsic activity. We examined the role of thalamic-derived factors in cortical development by selectively eliminating glutamatergic synaptic transmission from thalamocortical neurons in mice and found that eliminating thalamocortical neurotransmission prevented the formation of “barrel” columns in somatosensory cortex. Interestingly, based on cytoarchitectonic criteria and genetic markers, blocking thalamocortical neurotransmission also perturbed the development of superficial cortical lamina and the morphologic development of neurons. These experiments demonstrate that barrels and aspects of the layer-dependent pattern of cortical cytoarchitecture, gene expression, and neuronal differentiation depend on thalamocortical neurotransmission, extending the apparent influence of extrinsic, presumably activity-dependent factors, on cortical development. [Display omitted] •Glutamate release from thalamocortical neurons is required for barrel formation•Laminar development of cortex disrupted without thalamocortical neurotransmission•Morphology of cortical layer 4 spiny stellate cells also aberrant without glutamate•Extrinsic factors shape cortical columnar, laminar, and neuronal development Li et al. show that the basic features of cortical laminar and columnar development emerge under the influence of thalamocortical activity and suggest a much broader role for extrinsic, activity-dependent factors in the development of sensory neocortex than was previously appreciated.