Mountcastle proposed the cortical column based on observations made by recording from single cells, but he was influenced strongly by new ideas about the anatomy of the cortex. In the discussion section of his original report, he referred to recent work by Sperry & Lorento de Nó. The latter had reconstructed the complete morphology of single cells using the Golgi method to unravel the circuitry uniting different cortical layers. Tracing synaptic relationships, Lorento de Nó was struck by the predominance of vertical, rather than horizontal connections between cells in the cortical layers. This impression led him to suggest that a vertical cylinder containing all the elements of the cortex ‘may be called an elementary unit
, in which, theoretically, the whole process of the transmission of impulses from the afferent fibre to the efferent axon may be accomplished’ (Lorento De Nó 1949, p. 304
). Mountcastle's physiological data emphatically supported this view of the cortex as a conglomeration of independent vertical processing machines. It also seemed to explain an amazing series of lesion experiments by Sperry et al. (1955)
, in which they sliced the visual cortex of cats into pieces with tantalum wires (). Despite severance of long-range horizontal projections, the cats could still make fine visual discriminations. It was presumed that vision remained normal because the vertically organized columns required for cortical function were still intact.
Figure 2 Implanted wires in the cat's visual cortex produce no disturbance in form perception. (a) X-rays of a formalin-fixed cat brain showing segments of tantalum metal inserted months before death to sever horizontal projections. This procedure produced no (more ...)
The first apparent confirmation of Mountcastle's discovery of cortical columns came from Hubel & Wiesel's (1962
) pioneering studies in the primary visual cortex. They observed that cells recorded simultaneously at any given electrode site invariably had the same receptive field orientation. Moreover, when they advanced an electrode along a penetration perpendicular to the cortical surface, successively recorded cells shared an identical orientation of their receptive field axis. Hubel & Wiesel concluded that striate cortex contains a system of orientation columns superimposed on the 2D representation of the visual field. They drew a parallel with the columns identified by Mountcastle, but noted an important difference. In the somatosensory cortex, the columns arise from different types of peripheral receptors (e.g. Golgi tendon organs versus Meissner's corpuscles). In the visual cortex, by distinction, the orientation columns are generated by patterns of intrinsic wiring between afferents and cortical cells, but originate from the same receptors in the retina.
Mountcastle reported an abrupt transition from one submodality to another in electrode penetrations through the cat somatosensory cortex. This observation established a cardinal property of the cortical column: it is quantal. A column has a sharp (or at least a definite) border and all cells within it share some common, salient property. To see if orientation columns satisfy these criteria, Hubel & Wiesel (1963)
plotted the preferred orientation of cells encountered successively during long tangential electrode penetrations through cat visual cortex. As the electrode advanced, they formed the impression by listening to multiunit activity on an audio monitor that the preferred orientation of cells shifted in steps of 15°. Orientation tuning, therefore, appeared to change abruptly from one column to the next, conforming to Mountcastle's stipulation that columns are discrete. In the cat, 12 orientation columns were calculated to exist in a full rotation of 180°. Later, recording in the macaque, Hubel & Wiesel had more difficulty convincing themselves that columns were truly discrete because the preferred orientation seemed to shift with even the smallest electrode advance. Ultimately, they were persuaded by occasional, large jumps in orientation preference to stick with the idea that orientation columns are quantal. However, they conceded that if orientation varies continuously, ‘either one must broaden the definition of the column or decide that the system is not strictly columnar’ (Hubel & Wiesel 1974a, p. 289
). Tacitly, the definition of the column has been broadened over subsequent years to include structures without distinct borders. This usage acknowledges the reality that many periodically iterated structures in the cortex have gradual boundaries. It seems unproductive to worry too much about how sharp a column's boundary must be to qualify still as a column.
Hubel & Wiesel (1974a)
reported that shifts of 9 to 10° in orientation tuning occurred with electrode advances through the macaque striate cortex of only 25–50
μm (). Their data suggested that orientation columns might be extremely thin—perhaps only a single cell wide. If so, by definition, orientation columns would be quantal. In Nissl-stained sections, prominent bands of cells are visible running radially through the cortical layers (). To test the relationship between these palisades of cells and orientation columns, Hubel & Wiesel (1974a)
analysed a tangential electrode penetration made through striate cortex. They found 22 orientation shifts along a traverse of 32 cell bands, ruling out a direct, one-to-one correspondence. In retrospect, the comparison was not valid, although it led to the correct conclusion. Subsequent studies have shown that at any given recording site, neurons display scatter in their preferred orientation and are often broadly tuned (Hetherington & Swindale 1999
; Ringach et al. 2002
). It has become clear that orientation columns are not discrete entities, and therefore that Hubel and Wiesel's designation of 22 orientation shifts was arbitrary. Orientation tuning does exhibit occasional fractures and singularities (pinwheels)—which convinced Hubel and Wiesel that orientation is quantal—but in fact, optimal orientation varies smoothly across most of the cortical surface (Albus 1975
; Blasdel & Salama 1986
). Therefore, Hubel and Wiesel's classic model showing orientation columns as discrete slabs is misleading because the columns are borderless in real life. The diagram is still useful, however, because it captures an early view of how multiple column systems in the primary visual cortex might be organized.
Figure 3 Hubel and Wiesel's ice cube tray model of the striate cortex. In oblique microelectrode penetrations, they attributed the regular shift in orientation preference to an orderly stacking of slab-like orientation columns. Orientation hypercolumns contained (more ...)
Figure 4 Ontogenetic columns extend from white matter into cortex. A cross-section through macaque somatosensory cortex stained for Nissl substance shows radial stacks of cells extending from the white matter into the cortical layers. These remnants of foetal (more ...)
Although the prominent cell bands seen in Nissl sections do not represent individual orientation columns, they provide persuasive evidence that the adult cortex is composed of discrete, elementary units generated during development. Across many species and cortical regions, these bands have a width of between 30 and 80
μm and contain a few hundred cells (Rockel et al. 1980
). Rakic (1971)
has shown by [3
H]thymidine autoradiography in foetal monkeys that neurons destined for the neocortex are born in a proliferative region near the cerebral ventricles. This ventricular zone contains radial glia, which are stem cells for neurons (Noctor et al. 2001
; Tamamaki et al. 2001
; Anthony et al. 2004
). After birth, neurons migrate successively along a scaffold provided by radial glia into the cortical plate, passing earlier arrivals to generate the layers in an inside-out fashion (Angevine & Sidman 1961
). This process produces vertical stacks of cells, divided by glial septa, which extend from the white matter to the pial surface. Rakic (1988)
has called these palisades of cells ‘ontogenetic columns’. Studies of cell lineage using a retroviral vector carrying the β-galactosidase marker gene have suggested that tangential migration of neurons also occurs in the developing cortex (Walsh & Cepko 1988
). This observation may be explained by lateral displacement of progenitor cells in the ventricular zone (Reid et al. 1995
) and by tangential movement of young neurons through the cortex (O'Rourke et al. 1995
). The relative amount that cells travel radially versus laterally through the developing cortex has been controversial; it clearly varies by species, cell type, brain region and developmental stage (Marin & Rubenstein 2003
). In the final analysis, although tangential migration of neurons is an important feature of cortical development, the predominant pattern of cell movement is vertical (), as proposed by the radial unit hypothesis of cortical formation (Rakic 1995
Figure 5 Formation of radial minicolumns or ontogenetic columns. (a) Progenitor cells in the ventricular zone (VZ) give rise to progeny that migrate in succession along a glial scaffold into the cortical plate (CP). These cells remain roughly aligned along their (more ...)
From the standpoint of cortical processing, the crucial question is whether the radial cell units generated during development correspond in any sense to the functional columns proposed to exist in the mature brain. The original columns identified in the adult cat somatosensory cortex by Mountcastle were much larger than the radial units identified by Rakic—by an order of magnitude. Aware of this dilemma, Mountcastle (1978, p. 37)
later invoked a new entity: the minicolumn. He stated, ‘I define the basic modular unit of the neocortex as a minicolumn. It is a vertically oriented cord of cells formed by the migration of neurons from the germinal epithelium of the neural tube along the radial glial cells to their destined location in the cortex, as described by Rakic’. In a subsequent review article, Rakic (1988, p. 176)
seemed to agree, asserting that ‘ontogenetic columns become basic processing units in the adult cortex’. He then stipulated, in a rather contradictory footnote, ‘the ontogenetic columns…should not be confused with the minicolumns’. Ultimately, however, Rakic (personal communication) has embraced the idea that the minicolumns of Mountcastle and the radial ontogenetic columns are closely related, as they must be, according to a literal interpretation of Mountcastle's definition.
If the minicolumn is truly the basic unit of the cortex, then what about the column, originally proposed as the elementary physiological unit? If two different structures are defined as the fundamental unit of the cortex, then there is potential for confusion. Mountcastle (1997, p. 701)
solved this dilemma by subsequently linking the two structures, declaring that a column is ‘formed by many minicolumns bound together by short-range horizontal connections’. The larger structure, the ‘column’, has been redefined by others as a ‘macrocolumn’ (Buxhoeveden & Casanova 2002
). Whichever label one prefers, the concept that minicolumns are bound together like sticks in a fascicle to form larger functional units has several problems. First, nobody seems willing to venture how many minicolumns constitute a column; the number is arbitrary. Second, there is no evidence that short-range connections bind minicolumns into discrete, larger structural entities. In the visual cortex, for example, injection of a tracer at any site labels a diffuse cloud of local connections of about 500
μm in diameter (Callaway 1998
; Lund et al. 2003
). These short-range connections do not end abruptly along fixed borders in the cortex, as they should if they actually defined the edges of a structurally distinct column. It is true that long-range connections in the cortex terminate in clusters. These clusters unite groups of cells sharing the same receptive field properties (Gilbert & Wiesel 1989
; Bosking et al. 1997
; Sincich & Blasdel 2001
). Such regular, patchy intracortical connections constitute a type of columnar structure, as discussed further below. They lend no support, however, to the theory that the cortical column is a distinct unit composed of an aggregate of minicolumns.
Equally dubious is the concept that minicolumns are basic modular units of the adult cortex, rather than simply remnants of foetal development. The concept derives from the observation that minicolumns are isolated by cell-sparse zones of neuropil into semi-distinct compartments. However, one could also assert that minicolumns are united by synapse-rich zones of neuropil, linking them seamlessly in the cortical sheet. The ‘elementary unit’ hypothesized by Lorento de Nó remains an elusive quarry. No one has demonstrated a repeating, canonical cellular circuit within the cerebral cortex that has a one-to-one relationship with the minicolumn. Moreover, there is little reason to believe that individual minicolumns are discrete functional entities like cortical columns are. If they were, cells in the same minicolumn would share receptive field properties, and these properties would differ from those found in adjacent minicolumns. As mentioned above, Hubel & Wiesel (1974a)
made a valiant attempt to correlate orientation columns with minicolumns but found no relationship. Swindale (1990)
has pointed out that no stimulus property has ever been shown to be represented in the cortex in a physiologically discrete manner on a scale compatible with the minicolumn. Buxhoeveden & Casanova (2002)
have taken issue with this assertion, citing evidence for discrete minicolumn function adduced by Favorov et al. (1987)
in cat somatosensory cortex. The latter investigators found occasional abrupt shifts in receptive field location, thought to occur at microelectrode transitions from one ‘segregate’ to another. The ‘segregate’—a new term introduced by Favorov—turns out to be a structure about 350–600
μm wide and resembles precisely a Mountcastle column. Therefore, the study by Favorov and colleagues provides evidence confirming Mountcastle et al.'s (1955)
original observations about columns, but does not address the functional properties of minicolumns. It remains true that nothing is known about the physiological correlates (if, indeed, any exist) of the minicolumn.
Why have there been virtually no studies probing the physiology of the cortical minicolumn? A major impediment is the poor spatial resolution of the extracellular recording method. Often, the same spike can be picked up over a traverse of 100
μm, depending to some extent on the electrode impedance, construction and tip shape (Mountcastle et al. 1957
; Rosenthal et al. 1966
). With such uncertain localization, it would be impossible to show that a receptive field property differs systematically from one minicolumn to the next, even if it did. It is also difficult to orient electrode penetrations in a perfectly radial or tangential trajectory and to reconstruct tracks reliably for post-mortem correlation of physiological properties and histological findings. Such inherent limitations have plagued efforts to show that the minicolumn (or the column for that matter) has distinct properties and borders. Two-photon imaging of calcium fluxes allows one to study intact neuronal circuits in vivo
with the resolution of individual cells (Stosiek et al. 2003
). The advent of this technique may finally allow one to probe the functional properties of the minicolumn.