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ScienceWeek
NEUROSCIENCE: ON REVISION OF THE NEURON DOCTRINE
The following points are made by T.H. Bullock et al (Science 2005 310:791):
1) After a century, neuroscientists are rethinking the Neuron Doctrine, the fundamental principle of neuroscience. This proposition, developed primarily by the great Spanish anatomist and Nobel laureate Santiago Ramon y Cajal (1852-1934), holds that a neuron is an anatomically and functionally distinct cellular unit that arises through differentiation of a precursor neuroblast cell. In principle, part of this tenet has held up, but technology and research have extended our knowledge far beyond this simple description. What has evolved is a modern view of the neuron that allows a more broad and intricate perspective of how information is processed in the nervous system. One hundred years since its inception, an examination of the Doctrine indicates that it no longer encompasses important aspects of neuron function. If we are to understand complex, higher level neuronal processes, such as brain function, we need to explore beyond the limits of the Neuron Doctrine.
2) In the early 20th century, the nervous system was thought to function as a web of interconnected nerve fibers. The cytoplasm and nervous impulses were thought to flow freely in any direction through the network of fibers. But it was Cajal who envisioned the neuron as an individual functional unit, polarized such that signals are received through its rootlike dendrites and transmitted through its long axonal process. He posited that although an axon terminates adjacent to a dendrite of the next neuron, the cleft between them would act as a synaptic switch regulating information flow through neural circuits. The synaptic cleft went unseen until a half-century later, when in 1954 the electron microscope provided convincing evidence that essentially refuted the earlier "reticular" view of a nerve fiber web [1].
3) At the same time, physiological studies established that conduction of electrical activity along the neuronal axon involved brief, all-or-nothing, propagated changes in membrane potential called "action potentials". It was thus often assumed that neuronal activity was correspondingly all-or-nothing and that action potentials spread over all parts of a neuron. The neuron was regarded as a single functional unit: It either was active and "firing" or was not.
4) This dogma began to erode with the advent of microelectrodes that could be inserted into neurons to record electrical signals. In 1959, it was realized that much of the information processing by neurons involves electrical events that are graded in amplitude and decay over distance, rather than all-or-nothing electrical spikes that propagate regeneratively [2]. It was also determined that evoked electrical responses often occur on a background of spontaneous changes in membrane potential (i.e., produced without input from other neurons) and that some parts of the neuron are incapable of producing all-or-nothing action potentials [3]. Today, it is apparent that information processing in the nervous system must operate beyond the limits of the Neuron Doctrine as it was conceived. This has evolved from detailed information gained from techniques developed in the past 50 years -- notably single-channel recording, live-cell imaging, and molecular biology.[4,5]
References (abridged):
1. E. D. P. De Robertis, H. S. Bennett, J. Biophys. Biochem. Cytol. 1, 47 (1955)
2. T. H. Bullock, Science 129, 997 (1959)
3. T. H. Bullock, Proc. Natl. Acad. Sci. U.S.A. 94, 1 (1997)
4. S. Ramon y Cajal, Histology of the Nervous System of Man and Vertebrates, N. Swanson, L.W. Swanson, Trans. (Oxford Univ. Press, New York, 1995)
5. M.V. L. Bennett, R. S. Zukin, Neuron 41, 495 (2004)
Science http://www.sciencemag.org
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ON THE DENDRITES OF NERVE CELLS
The following points are made by Y-N. Jan and L.Y. Jan (Genes & Dev. 2001 15:2627):
1) When connections in the central nervous system are effected, the axon of presynaptic neurons need to be properly guided to make synapses with the correct targets, which are usually the dendrites of the postsynaptic neurons. Dendrites are not just passive participants in this process, and most likely, synapse formation involves two-way communications between the presynaptic cell and the postsynaptic cell.
2) It is worth noting that not all dendrites receive synaptic input. For example, the dendrites of many sensory neurons are sensory endings that transduce signals from the external environment, such as mechanical or chemical stimuli. These sensory stimuli induce receptor potentials in the dendrite analogous to the synaptic potentials generated at the synapse. Regardless of whether they receive sensory or synaptic input, the dendrites are effectively the antennae of neurons. The dendritic branching pattern varies to a great extent with the neuronal type, and is an important determinant of the synaptic or sensory input received by a neuron.
3) Dendrites pose some extremely interesting problems from several different perspectives. From the developmental biological point of view, the dendrite branching pattern is a hallmark of neuronal type. Even neighboring neurons may exhibit strikingly different dendritic branching patterns. For example, on the basis of the dendritic branching pattern alone, the amacrine cells (one class of interneurons) in the rabbit retina can be subdivided into at least 20 different subtypes. By extrapolation, using solely dendrite morphology as a criterion, one could easily define hundreds or thousands of different types of neurons in the mammalian central nervous system.
4) From the cell biological point of view, the elaborate and stereotyped dendritic branching of a neuron is a striking example of pattern formation and morphogenesis. For example, a Purkinje cell in the cerebellum can elaborate remarkably complex yet stereotyped dendrites, and the cellular mechanisms controlling the formation of these elaborate cellular structures are likely to have some unique features and differ substantially from those regulating the formation of other highly branched structures such as the trachea or blood vessels, since those tubular structures are formed by the collaboration of multiple cells, each with simpler morphology.
Genes & Development http://www.genesdev.org
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ON THE COMPLEX FUNCTIONALITY OF NERVE CELL DENDRITES
The following points are made by D-S. Wei et al (Science 2001 293:2272):
1) Dendrites are not passive antennae that simply receive synaptic inputs: instead, dendrites actively process and transform inputs as they are received. The apical dendritic arbor can be divided into 3 morphologically distinct regions: the thick main apical trunk, a set of short intermediate branches, and a set of long and thin terminal branches. The apical trunk of pyramidal cell dendrites is relatively thick and contains sufficient densities of sodium channels to mediate forward and backward propagation of action potentials. Terminal branches, in contrast, have diameters one-fourth that of the apical trunk and do not decrease over distance. Terminal dendritic segments constitute 70 to 90 percent of the combined length of the apical dendritic arbor.
2) Despite being the main recipient of excitatory synaptic inputs, little is known about the passive and active transformations an individual terminal segment performs on its inputs. The authors report that the excitability of terminal apical dendrites in pyramidal cells of the rat hippocampus differs from that of the apical trunk. In response to fluorescence-guided focal photolysis of caged glutamate, individual terminal apical dendrites generated cadmium-sensitive all-or-none responses that were subthreshold for somatic action potentials.
3) Calcium transients produced by all-or-none responses were not restricted to the sites of photolysis, but occurred throughout individual distal dendritic compartments, indicating that electrogenesis is mediated primarily by voltage-gated calcium channels. The authors suggest that compartmentalized and binary behavior of parallel-connected terminal dendrites can greatly expand the computational power of a single neuron.
Science http://www.sciencemag.org
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EVIDENCE FOR COMPUTATIONAL FUNCTION OF NEURON DENDRITES
Notes by ScienceWeek:
Compared to the cells of other tissues, nerve cells exhibit extreme variation in shape (morphology), and one of the central problems of neurobiology is to relate the shapes of various types of nerve cells to specific functions (see the background material below). The auditory system of mammals is one of the better characterized neurophysiological systems, investigated for more than a century, and with certain parts of the system exquisitely defined by experimental procedures.
The basic function of the auditory system of mammals is to receive and analyze input sound vibrations, and one cardinal aspect is sound localization. In the auditory regions of the brainstem, there are neurons that act as "coincidence detectors" -- binaural neurons that respond maximally when they receive simultaneous inputs from the two ears, and these neurons are an essential part of the analytical system responsible for sound localization by the brain.
Essentially, coincidence-detector neurons in the auditory brainstem of mammals and birds use interaural time differences to localize sounds, each neuron receiving many narrow-band inputs from both ears and comparing the time of arrival of the inputs with an accuracy of 10 to 100 microseconds. Neurons that receive low-frequency auditory inputs (up to approximately 2 kHz) have bipolar dendrites (see discussion of dendrites in background material below), and each dendrite receives inputs from only one ear.
The following points are made by Agmon-Snir et al (Nature 1998 393:268):
1) The authors present a simple model that mimics the essential features of the known electrophysiology and geometry of these bipolar coincidence detector neurons, and they report that the model supports the idea that dendrites improve the coincidence detection properties of these cells, enriching the "computational power" of these neurons beyond that expected from model neurons lacking dendrites.
2) The significance of this research is that it relates in a highly quantitative manner the relation between the modeled dendritic morphology of a particular type of nerve cell and its function, and the authors suggest their approach might be used as a paradigm for the study of dendritic morphology-function relations in other types of nerve cells.
Nature http://www.nature.com/nature
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