Functional imaging with cellular resolution reveals precise micro-architecture in visual cortex

Abstract

Neurons in the cerebral cortex are organized into anatomical columns, with ensembles of cells arranged from the surface to the white matter. Within a column, neurons often share functional properties, such as selectivity for stimulus orientation; columns with distinct properties, such as different preferred orientations, tile the cortical surface in orderly patterns. This functional architecture was discovered with the relatively sparse sampling of microelectrode recordings. Optical imaging of membrane voltage or metabolic activity elucidated the overall geometry of functional maps, but is averaged over many cells (resolution >100 microm). Consequently, the purity of functional domains and the precision of the borders between them could not be resolved. Here, we labelled thousands of neurons of the visual cortex with a calcium-sensitive indicator in vivo. We then imaged the activity of neuronal populations at single-cell resolution with two-photon microscopy up to a depth of 400 microm. In rat primary visual cortex, neurons had robust orientation selectivity but there was no discernible local structure; neighbouring neurons often responded to different orientations. In area 18 of cat visual cortex, functional maps were organized at a fine scale. Neurons with opposite preferences for stimulus direction were segregated with extraordinary spatial precision in three dimensions, with columnar borders one to two cells wide. These results indicate that cortical maps can be built with single-cell precision.

Delayed plasticity of inhibitory neurons in developing visual cortex

“…A recently developed extracellular injection technique has made it possible to load all or nearly all neurons in a 200-to 300-m region of cortex with a cell-permeant version of the calcium indicator OregonGreen BAPTA-1 (OGB-1) (13,14). This technique has been applied successfully to the study of neuronal response properties in rodent visual cortex (15)(16)(17).…”

Organisation dendritique et caractéristiques fonctionnelles des afférences visuelles sur les neurones corticaux

“…Ces résultats donnent également des indices sur les règles qui régissent le développement des connexions neuronales dans le cortex visuel. Dans le cortex visuel des rongeurs, les neurones ayant des sélectivités d'orientation différentes sont distribués de façon aléatoire [10] et non pas organisés en colonnes comme chez les mammifères supérieurs (chat, furet, primates, par exemple) [3,11,12]. L'arrangement apparemment aléa-toire des afférences synaptiques décrit ci-dessus pourrait donc provenir du fait que chaque neurone reçoit des afférences synaptiques de ses voisins de façon aléa-toire.…”

MRI contrast agents for functional molecular imaging of brain activity

“…Recent two-photon fluorescence imaging studies have demonstrated the power of calcium measurements to characterize neuronal population behavior in exposed regions of the brain [12,13]. MRI indicators for calcium can facilitate calcium imaging of deep tissue structures.…”

“…The technique involves following the kinetics of a 13 C-labeled metabolite, pyruvate, by 13 C MRI ( Figure 1D). Normally, 13 C MRI is too insensitive to detect pyruvate at physiologically relevant concentrations, but here the authors used a method called dynamic nuclear polarization to boost the MRI signal from 13 C 1 -pyruvate using a specialized device [37]. Kinetics of pyruvate uptake and turnover to lactate and alanine were followed in the muscles and abdominal organs of rats and pigs.…”

“…Most MRI contrast agents are paramagnetic chemicals that increase parameters called the T 1 and T 2 relaxation rates of water, as observed in tissue and solution; T 1 or T 2 relaxation enhancements produce image brightening or darkening, respectively. Additional classes of contrast agents work by a chemical exchangebased mechanism called CEST [5], or involve imaging nonstandard nuclei like 19 F and 13 C. The characteristics and physical mechanisms of different types of contrast agent are discussed at length in a number of book chapters and reviews [6][7][8][9][10][11], and are summarized in Figure 1. In general, for any agent to be used in functional imaging, either its ability to influence MRI contrast or its spatial distribution must be sensitized to neural activity in some way.…”