Clonally Related Visual Cortical Neurons Show Similar Stimulus Feature Selectivity

A fundamental feature of the mammalian neocortex is its columnar organization(1). In the visual cortex, functional columns consisting of neurons with similar orientation preference have been characterized extensively(2-4), but how these columns are constructed during development remains unclear(5). The ‘radial unit hypothesis’(6) posits that the ontogenetic columns formed by clonally related neurons migrating along the same radial glial fiber during corticogenesis(7) provide the basis for functional columns in adult neocortex(1). However, direct correspondence between the ontogenetic and functional columns has not been demonstrated(8). Here we show that, despite the lack of discernible orientation map in mouse visual cortex(4,9,10), sister neurons in the same radial clone exhibit similar orientation preference. Using a retroviral vector encoding green fluorescent protein (GFP) to label radial clones of excitatory neurons and in vivo two-photon calcium imaging to measure the neuronal response properties, we found that sister neurons preferred similar orientations, while nearby non-sisters showed no such relationship. Interestingly, disruption of gap junction coupling by viral expression of a dominant-negative mutant of Cx26 or by daily administration of a gap junction blocker carbenoxolone (CBX) during the first postnatal week greatly diminished the functional similarity between sister neurons, suggesting that the maturation of ontogenetic into functional columns requires intercellular communication through gap junctions. Together with the recent finding of preferential excitatory connections among sister neurons(11), our results support the radial unit hypothesis and unify the ontogenetic and functional columns in the visual cortex.