Krieger Mind-Brain Institute, Department of Neuroscience, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA
Address correspondence to V.B. Mountcastle, Krieger Mind-Brain Institute, Department of Neuroscience, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA. Email: mountcastle{at}mbi.mb.jhu.edu.
Every neuroscientist has a list of those he considers the most important unsolved problems in brain science. Surely high on the list of many will be that considered in this issue of Cerebral Cortex. Namely, what are the transforming operations imposed in a local region of neocortex, a cortical column, upon its input to produce its several outputs? The essays included here provide a cross-section of this large field, written by investigators using methods that include Golgi studies, slice recording with multiple intracellular microelectrodes and multiple microelectrode recording in intact cortex; several include theoretical modeling. While no one of these authors would venture that the problem is solved, their contributions and those of others in the field indicate that significant progress has been made in constructing an intra-columnar flow diagram, and in understanding the dynamic neuronal operations within it.
When in 19551959 I described the columnar organization of the somatic sensory cortex on the basis of observations made in single neuron recording experiments in cats and monkeys (Mountcastle et al., 1955; Mountcastle, 1957
; Powell and Mountcastle, 1959
), the report was met with disbelief by many neuroanatomists. This was so because the histological methods available at the time revealed no structural counterpart to match the physiological observations. Lorente de No had described, in 1949, synaptically linked, trans-laminar, chains of neurons in the rodent cortex, which he postulated to be an elementary unit of the neocortex. Several anatomists had described cords of cells oriented normally to the pial surface, like those in the human auditory cortex described by von Economo, who first used the word column to describe them (von Economo and Koskinas, 1925
). The Golgi method Lorente de No used revealed no sign of the horizontal disjunctions in functional properties we now know to characterize columnar organization, and to group sets of minicolumns into columns. I quote him directly, for Fultons textbook of Neurophysiology is not now widely available.
If use is made of the elementary unit introduced previously, it may be said that the cortex is composed of an enormous number of elementary units, not simply juxtaposed but overlapping [my emphasis]. Each elementary unit has a series of axonal and dendritic plexuses, where the synapses between intracortical elements and afferent fibres with cortical cells are established. The bodies of the cells which form similar links in the intracortical chains are grouped in horizontal layers. Therefore any change in the constitution of the intracortical chains must produce a variation in the density of the plexuses, i.e., in the Nissl pattern, in the size of the empty [sic] intracellular spaces, and likewise in the number of cells in each layer. (Lorente de No, 1949)
It is clear from these perceptive generalizations, and the more detailed descriptions given in Lorente de Nos essay, that he recognized what we now term the cortical minicolumn, and he envisaged how variations of cell number and type at different depths in different areas could account for the cytoarchitectural differences then well known for many decades. However, Lorente de No could not recognize the abrupt transitions in functional properties which separate one column from the next.
Perhaps disbelief should have been expected, for the proposals were foreign to prevailing views of cortex. They were, firstly, that a vertical organization exists at cross-axis to and indeed accounts for the laminar organization of the cortex, and, secondly, that the cortex consists of a large number of units much smaller than cytoarchitectural areas. The concepts of laminar organization and the division of the cortex into cortical organs defined by cytoarchitectural differences were dominant. The idea was then widely held, and still is by some, that different laminae might be specialized for different functions. The physiological observations made in the somatic sensory cortex in cats and monkeys, and in the visual cortex of both species by Hubel and Wiesel (Hubel and Wiesel, 1959, 1968
, 1977
) suggested two facts then unknown. Firstly, that the terminations of afferent systems to the cortex, whether from the thalamus or from other cortical areas, are arranged in clusters of sub-millimeter dimensions. Secondly, it was postulated on the basis of the latency measurements that the imposed cortical input is relayed rapidly in the vertical dimension, but restricted in the horizontal (i.e. parallel to the pial surface) dimension, and that it engages both pyramidal cells and interneurons after no more than one or two intracortical synapses. Evidence was presented that a pericolumnar inhibition might lend a dynamic tone to columnar isolation, although the cortical inhibitory interneurons were then unknown.
In the years since 19551959 the columnar or modular organization of the neocortex has been documented in studies of sensory, motor and homotypical areas under many experimental conditions and in many species, including the waking, behaving monkey. The requirements given above have been met in many anatomical and physiological experiments. The generally agreed state of knowledge can be summarized in a series of brief statements, as follows. The basic unit of cortical operation is the minicolumn, Lorente de Nos elementary unit. It contains of the order of 80100 neurons, except in the primate striate cortex, where the number is more than doubled. The mini-column measures of the order of 4050 µm in transverse diameter, separated from adjacent minicolumns by vertical, cell-sparse zones which vary in size in different cortical areas. Each minicolumn has all cortical phenotypes, and each has several output channels. The minicolumn is produced by the iterative division of a small set of progenitor cells in the neuro-epithelium, probably via the interim ontogenetic unit described by Rakic (Rakic, 1972, 1988
, 1995
). By the 26th gestational week the human neocortex is composed of a large number of minicolumns in parallel vertical arrays. This remarkable regularity is revealed in histological sections closely aligned with the vertical axes of minicolumns; see Figure 3 in (Buxhoevedan and Casanova, 2002). Moreover, optical density measurements reveal the oscillating changes in cell density in the horizontal dimension, with periods at the minicolumn diameter of 4050 µm (Schlaug et al., 1995
).
Cortical columns are formed by the binding together of many minicolumns by common input and short range horizontal connections. The number of minicolumns per column varies, probably because of variation in size of the cell sparse inter-minicolumnar zones; the number varies between 50 and 80. Long-range, intracortical projections link columns with similar functional properties. Columns vary between 300 and 500 µm in transverse diameter, and do not differ significantly in size between brains that vary in size over three orders of magnitude (Bugbee and Goldman-Rakic, 1983). Cortical expansion in evolution is marked by increases in surface area with little change in thickness; how columns are recruited to form new areas is a matter of much study and speculation, but is still uncertain. Columnar organization allows for intermittently recursive mapping, so that two or more variables can be mapped to the single xy dimension of the cortical surface (Mountcastle, 1997
, 1998
; Buxhoeveden and Casanova, 2002
).
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Are Properties Identical For All Neurons in a Minicolumn? |
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Are Minicolumns in Different Cortical Areas All the Same? |
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How Can the Intrinsic Function of the Cortex Be Studied? |
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A second problem is the choice of experimental preparation. Most of the essays in this issue describe studies of the rodent barrel cortex, or the striate cortex of cats or monkeys, which are among the most highly specialized cortical formations in all of cortex. Moreover, some of the experiments described were made in slice preparations, and bear the further shadow that most were done in immature cortex. Yet we know that intra-cortical connectivity changes in major ways between birth and maturity. The answer to many problems may come from studies of the primate homotypical cortex, now under way in many laboratories.
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What Generalizations Can Be Made? |
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References |
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