In Vivo Functional Mapping of a Cortical Column at Single-Neuron Resolution

The cerebral cortex is organized in vertical columns that contain neurons with similar functions. The cellular micro-architecture of such columns is an essential determinant of brain dynamics and cortical information processing. However, a detailed understanding of columns is incomplete, even in the best studied cortical regions, and mostly restricted to the upper cortical layers. Here, we developed a two-photon Ca ²⁺ -imaging-based method for the serial functional mapping of all pyramidal layers of the mouse primary auditory cortex at single-neuron resolution in individual animals. We demonstrate that the best frequency-responsive neurons are organized in all-layers-crossing narrow columns, with fuzzy boundaries and a bandwidth of about one octave. This micro-architecture is, in many ways, different from what has been reported before, indicating the region and stimulus specificity of functional cortical columns in vivo. Tischbirek et al. report a two-photon Ca ²⁺ -imaging-based approach to map sensory-evoked neuronal activity from L2/3 to L6 of mouse cortex. In the primary auditory cortex, the authors identify functional microcolumns at cellular resolution that bring together large-scale tonotopy and locally heterogeneous frequency responses throughout all cortical layers.