The Functional Microarchitecture of the Mouse Barrel Cortex

Abstract

Cortical maps, consisting of orderly arrangements of functional columns, are a hallmark of the organization of the cerebral cortex. However, the microorganization of cortical maps at the level of single neurons is not known, mainly because of the limitations of available mapping techniques. Here, we used bulk loading of Ca²⁺ indicators combined with two-photon microscopy to image the activity of multiple single neurons in layer (L) 2/3 of the mouse barrel cortex in vivo. We developed methods that reliably detect single action potentials in approximately half of the imaged neurons in L2/3. This allowed us to measure the spiking probability following whisker deflection and thus map the whisker selectivity for multiple neurons with known spatial relationships. At the level of neuronal populations, the whisker map varied smoothly across the surface of the cortex, within and between the barrels. However, the whisker selectivity of individual neurons recorded simultaneously differed greatly, even for nearest neighbors. Trial-to-trial correlations between pairs of neurons were high over distances spanning multiple cortical columns. Our data suggest that the response properties of individual neurons are shaped by highly specific subcolumnar circuits and the momentary intrinsic state of the neocortex. Mice depend on their whiskers to explore their environment. Tactile receptors at the base of each whisker relay sensory information to a brain area called the barrel cortex. This somatosensory area consists of an orderly array of cortical columns, each containing clusters of neurons whose responses are driven primarily by stimulation of a particular whisker, in addition to stimulation of surrounding whiskers. The detailed structure of this cortical map, especially within a column, is poorly understood. We imaged multiple neurons loaded with calcium indicators to monitor whisker deflection-evoked action potentials in the barrel cortex of mice. Calcium imaging methods allowed us to reliably detect action potentials in approximately half of the cortical neurons. For these neurons, we measured the spiking probability following whisker deflection and thus created a high-resolution map of whisker selectivity. On average, the whisker map varied smoothly across the surface of the cortex. But the whisker selectivity of individual neurons differed significantly, even for neighboring neurons. The responses of neurons, even those that were distant from each other, were highly correlated across trials and depended on the level of overall brain activity at the time of the stimulus. Our data suggest that the response patterns of cortical neurons are determined by specific local circuits and by the global state of the cortex, which changes over time.