The identification of vertical and horizontal connections

The work of Mountcastle in somatosensory cortex (Mountcastle, 1957, 1997; Powell and Mountcastle, 1959) and Hubel and Wiesel in visual cortex (Hubel and Wiesel, 1962, 1968, 1977) established one of the fundamental principles of cortical organization: the orderly arrangement of cells with similar functional properties into vertically oriented columns traversing the cortex from pia to white matter. In visual cortex, the similarity in the response properties of neurons (e.g., orientation preference, ocular dominance, position in visual space) recorded along a vertical electrode penetration and the regular progression in response properties recorded along tangential penetrations led to the view that the elements of cortical circuitry critical for setting up these specific response properties are confined to the column (Hubel and Wiesel, 1962, 1968, 1977). Although the exact dimensions of the column were subject to some debate, the idea that response properties were generated from interactions within a relatively localized cortical region was consistent with the evidence from Golgi studies of Ramon y Cajal (1911), Lorente de No (1938), and Lund (1973; Lund and Boothe, 1975) showing a predominantly cylindrical arrangement of intracortical connections. Neurons in layer 4 of the macaque visual cortex, for example, give rise to axon arbors that ascend and produce terminal arbors that cover less than 1 mm of surface area in layer 2/3.

Fisken and colleagues (1975) were the first to recognize that some connections identified by degeneration techniques following cortical lesions extended for more than 1 mm across the cortical surface, but it was the work of Rockland and Lund (1982; Rockland et al., 1982) that provided the first clear picture of just how far this horizontal network could extend. Following injections of retrograde tracers into visual cortex in the tree shrew, these investigators demonstrated patches of labeled cells and terminals that were distributed over distances 3 to 4 mm from the injection site in cortical layer 2/3, covering a substantial fraction of V1 in this species. These initial observations were subsequently confirmed in other species (Matsubara et al., 1985, 1987; Rockland and Lund, 1983), and the elegant intracellular injection experiments of Gilbert and Wiesel (1983) and Martin and Whitteridge (1984) demonstrated that the bulk of these long-range connections originate from pyramidal neurons. Ultrastructural analysis also demonstrated that horizontal connections terminate on the dendritic processes of other pyramidal cells as well as smooth dendritic GABAergic neurons (McGuire et al., 1991). These anatomical observations received support from intracellular recordings in tissue slice experiments showing that electrical stimulation of horizontal connections can evoke both excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) at more distant sites (Hirsch and Gilbert, 1991; Weliky et al., 1995).