User:Eugene M. Izhikevich/Proposed/Cortical column
Dr. Nicholas V. Swindale, University of British Columbia, Vancouver, BC, Canada, was invited on 2 November 2008.
History (by Vernon Mountcastle)
By the year 1948-1949 Adrian’s method of single neuron analysis had become the dominant mode of research in CNS physiology. It is worth noting that virtually no one in the field was entranced by the study of single neurons, per se, but sought to reconstruct population events by studying neurons one by one. This of course lost what may be of critical importance, the time relations between impulse discharges of elements of the population, now under intensive study in the new century. Jerzy Rose and I began a program using this method in study of the somatic afferent system, beginning in the cat ventrobasal complex. We made a quantitative study of the response properties of thalamic neurons, but at this level of the system saw little other than a tenacious replication of the first order input, and no sign of what we hoped to find – some aspect of neuronal processing suggestive of perceptual operations (Rose and Mountcastle, 1954). During those long days and nights I learned a good deal about the history of Poland, and he something of Stonewall Jackson’s genius in the Valley Campaign.
We then took up separate studies of the cerebral cortex of the cat, Rose and his colleagues in the auditory cortex (Erulkar, et al., 1956), and I together with P.W. Davies and A.L. Berman in the somatic sensory cortex. It was necessary first to solve several technical problems. The first was how to achieve a stable relation between electrode and cortical neuron in an exposed cortex moving a mm or more with each beat of the heart! Some investigators did this by applying pressure plates to the cortex, but we found this had a depressing effect upon neurons in the outer cortical layers. Davies solved this by designing and constructing a microelectrode drive mounted in a glass plate. This was mounted as the top of a fluid filled cortical chamber; it could be moved to bring the electrode tip to any desired location (Davies, 1956). The surface of the cortex viewed via a dissecting microscope through the glass plate was stable – one could see the red cells go by! We then saw that even the finest microelectrode depressed the cortex before penetrating. I found that with especially designed tools (and a great deal of practice) I could dissect away the arachnoid from a desired zone of penetration, without damage to the underlying cortex. This allowed penetration of a microelectrode without depressing the cortical surface. We had only low-impedance input amplifiers, left over from Woolsey’s construction of a nine channel recording system for study of slow-wave evokced potentials. Without funds for new amplifiers, we sought a low-impedance microelectrode to match our amplifiers. This was designed by Dowben and Rose (1953): it was filled with indium and plated at the tip first with gold and then with platinum. It worked.
As a microelectrode moves into the field of the action potential discharges of a cortical neuron, it first enters a region of small, initially negative action potentials. When the electrode gets very close to or contacts the membrane of the cell, the action potential inverts to an initially positive and very large action potential – what P.O. Bishop called quasi-intracellular recording. I found it best to study the small negative action potentials, for the initially positive ones always showed signs of cell damage: changes in the pattern of spontaneous activity, decreased response to afferent input, etc.
My own results are given in two papers in 1957, the first with Davies and Berman, the second by me alone, in which I described the columnar organization of the cortex (Mountcastle, et al., 1957; Mountcastle, 1957). Many friends have asked why the second paper containing a description of this general principle is authored by me along. The answer is: by request! My two colleagues were so apprehensive over this new general principle that they requested that their names be left off the second paper, where I had originally placed them! Indeed, one can hardly exaggerate the calumny I was subjected to over this principle, and most vigorously by my colleague, J.E. Rose. The majority of anatomists of the period had been trained in the schools if Nissl cytoarchitecture, Rose by the Vogts themselves, and the concept of layered cytoarchitecture dominated the scene; some even designated different functions for different layers! This was all before the revival of Cajal-type studies of the cerebral cortex.
The idea of columnar organization came as one of those wonderful ‘a-ha’ experiences a research scientist rarely experiences. One day I sat tabulating in vertical lists the neurons observed in the previous day’s experiment. I had identified three classes of neurons in the somatic sensory cortex: those adapting slowly to skin pressure, those adapting rapidly, and those driven by joint rotation. It was immediately obvious that neurons of these three classes were not randomly distributed in my vertical lists. Different classes appeared in vertically arranged groups with sharp changes in cell type from block to block; and, for some penetrations, only a single class throughout the depth of the cortex. Columnar organization can be confirmed in any single experimental day. Microelectrode penetrations made perpendicularly to the cortical surface encounter neurons with similar properties of place and modality through the depth of the cortex. Penetrations made parallel to the cortical surface and crossing the vertical axis of the cortex pass through 200-300 μm blocks of tissue in each of which neurons with similar properties are encountered but which differ from block to block. These observations were confirmed over the next few years in long series of experiments first in anesthetized and later in waking monkeys (e.g., Powell and Mountcastle, 1959; for review, see Mountcastle, 1997).
During the following years the columnar organization was found to be the mode of organization in all heterotypical and homotypical areas of the neocortex, in a wide spectrum of mammals. It was then discovered that the elementary processing unit of the cortex is a narrow vertical array of neurons, an array with a diameter of about 80 microns; the columns described consist of bundles of minicolumns, bound by common afferent input (for reviews, see Casanova, 2005). This narrow vertical array contains all cortical cell types, and pyramidal neurons projecting axons into each of the major cortical efferent pathways. This appears to be a polyclone of the elementary building block of the cortex, the ontogenetic unit in the germinal epithelium described by Rakic (1988). There is considerable evidence that abnormalities in the structure of cortical minicolumns are the pathological base for several major cerebral disorders, including psychoses (Casanova, 2005).
- Casanova, M.F. (ed.) (2005) Neocortical Modularity and the Cell Minicolumn, Nova Biomedical Books, New York.
- Davies, P.W. (1956) Chamber for microelectrode studies in the cerebral cortex. Science 124: 179-180.
- Erulkar, S.D., J.E. Rose, and P.W. Davies (1956) Single unit activity in the auditory cortex of the cat. Johns Hopkins Hospital Bulletin 99:55-86.
- Dowben, R.M. and J.E. Rose (1953) A metal-filled microelectrode. Science 119:22-24.
- Mountcaslte, V.B. (1957) Modality and topographic properties of single neurons of cat’s somatic sensory cortex. J. Neurophysiol. 20:408-434.
- Mountcastle, V.B. (1997) The columnar organization of the cerebral cortex. Brain 120:701-722.
- Mountcastle, V.B., P.W. Davies and A.L. Berman (1957) Response properties of neurons of cat’s somatic sensory cortex to peripheral stimuli. J. Neurophysiol. 20:374-407.
- Powell, T.P.S. and V.B. Mountcastle (1959) Some aspects of the functional organization of the cortex of the postcentral gyrus of the monkey; a correlation of findings obtained in a single unit analysis with cytoarchitecture. Johns Hopkins Hospital Bulletin 105: 133-162.
- Rakic, P. (1990) Principles of cell migration (Review) Experientia 46:882-91.
- Rose, J.E. and V.B. Mountcastle (1954) Activity of single neurons in the tactile thalamic region of the cat in response to a transient peripheral stimulus. Johns Hopkins Hospital Bulletin 94:238-382.