What Does Cytochrome Oxidase Histochemistry Represent in the Visual Cortex?

Ever since Wong–Riley first reported in the late 1970s that histological staining using the chemical reactions of cytochrome oxidase (CO), a metabolic enzyme in the mitochondria, is useful to reveal the cytoarchitecture of the brain (Wong-Riley, 1979), the CO histochemistry method has been widely used in the field of neuroanatomy, especially in carnivores and primates. It has been suggested that CO activity is coupled with the spike activity of neurons (Wong-Riley, 1979). Most strikingly, the use of CO histochemistry was critical to the discovery of patchy functional sub-compartments in the supragranular layers of primate V1, which are referred to as “CO blobs/puffs/patches” (Horton, 1984). Additionally, CO histochemistry revealed sub-compartments of “thick stripes,” “thin stripes,” and “pale stripes” in the middle layer of the secondary visual cortex (V2), which have been shown to possess distinct connections with V1 and other cortical areas (Sincich and Horton, 2002). These three stripes are also functionally distinct, as binocular disparity coding neurons are clustered into thick stripes (Chen et al., 2008). As such, CO histochemistry has revealed many normally cryptic functional compartments of the mammalian brain. Nonetheless, in this article, we aim to question the interpretation of results from CO histochemistry as “activity maps” of the brain.