Contains reports on two research projects.Bell Telephone Laboratories, Inc.National Institutes of Health (Grant B-1865-(C3))National Institutes of Health (Grant MH-04737-02)The Teagle Foundation, Inc.U.S. Air Force (Aeronautical Systems Division) under Contract AF33(616)-778

Gesteland, R. C.

Lettvin, Jerome Y.

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XX. NEUROPHYSIOLOGY*W. S. McCulloch J. D. Cowan Diane MajorJ. A. Aldrich Herta von Dechend N. M. OnestoM. A. Arbib Rachel G. Fuchs W. H. PittsF. S. Axelrod R. C. Gesteland J. A. RojasM. Blum M. C. Goodall Paola M. RossoniJ..E. Brown K. Kornacker A. TaubEleanor K. Chance J. Y. Lettvin P. D. WallA. FORM-FUNCTION RELATIONS IN NEURONSNerve membrane communicates with itself by means of electric currents flowingfrom one part to another. The current is generated by a system of charge separationwhereby the two major cations, K + and Na + , can be gated differentially through the mem-brane. Since there is an energy storage across the membrane in the form ofa concentration-difference cell, the differential gating can be used to produce current.The energy storage is achieved by an ion pump, driven by metabolism, which expels Na+from the inside of the cell. The Na+ current generator runs continuously and is balancedby the passive diffusion of Na+ across the membrane. This distributed current genera-tor sets up an IR drop across the membrane through the passive diffusion path, and thepotential thus obtained across the membrane drives the freely diffusible ions, notpumped, such as K and C1-, to that equilibrium at which the potential between theirconcentration within the cell and without balances the potential generated by the pumpsystem. Thus, the energy storage is in part in the Na+ concentration difference, andin part in the concentration of the ions at equilibrium with the membrane potential. Thereare two possible effects from gating ions. If one gates an ion species at equilibrium withmembrane potential, there is no change in potential and no current flow. (Under condi-tions of applied external current, the increase of K+ conductance shows up as a shuntacross the membrane.) If one gates the ion with which the pump sets the membranepotential, then the membrane potential alters violently, for it will tend to come to theconcentration potential of that ion species and there will be a current of that ion. Forexample, Na+ has been pumped out of the cell against a gradient, until its diffusion intothe cell equals the rate at which it is extruded. If the rate at which it can diffuse intothe cell is then increased, the membrane potential changes and also produces an Na+current. Thus, as far as one piece of membrane can affect another electrically, itdoes so either by gating Na + ions and thus serves as a current generator, or by gatingK+ (or Cl-) and thus serves as a shunt (or both and serves as a partially shunted currentsource). Under these conditions, I suggest that subthreshold excitatory events tend toThis work was supported in part by Bell Telephone Laboratories, Inc.; the NationalInstitutes of Health (Grant B-1865-(C3), Grant MH-04737-02); The Teagle Foundation,Inc.; and in part by the U.S. Air Force (Aeronautical Systems Division) under ContractAF33(616)-7783.333(XX. NEUROPHYSIOLOGY)add to each other in a receiving cell, whereas an inhibitory event tends to shunt, ordivide, the excitation rather than subtract from it. This, in fact, seems to occur exper-imentally - in the well-known studies of Kuffler and Eccles on the character of inhibition.If the very cursory discussion given above gives a true picture, then the placementof synapses on a dendrite is not permutable. For, suppose that a single dendrite leadsto a cell body. Let an excitatory synapse occur at the tip. An inhibitory synapse any-where between the tip and the cell body will attenuate the excitatory signal. But if theinhibitory synapse also occurs distally, then excitors closer to the cell body will not beshunted by that inhibition. Rather, the constellation of inhibitors and excitors in thedistal portion of the dendrite, decoupled from the cell body by the resistive path downthe dendrite, will act as a current source of variable strength. The signal from thiscurrent source will be additive with that from the more proximal excitors. We alreadyhave experimental evidence to show additive and divisive inhibitions in the same cell.One should then be able to determine the crude order of connectivity to a cell by excitingits inputs by pairs. With this hypothesis, the effect of the array of endings along anidealized single dendrite is expressible crudely in terms of a set of nested fractions,as in the familiar Euclidean algorithm. But as soon as one considers a dendritic tree,the complexity increases greatly, and it is obvious that the nest of nested functions soexpressed is dictated by both the geometry of the tree and the order of its inputs. Thus,without any special appeal, or without requiring an exact statement of the character ofsynaptic transmission, but simply by virtue of the electrical effects that one piece ofmembrane can have on another, it is possible to show that the anatomy of a dendritic treehas a necessary relation to the function taken by that tree, and also that one can synthe-size such complex functions by the arrangement of current sources and shunts in a resis-tive tree. But the implication is also that any function that can be expressed by afractional expansion can be expressed by a dendritic tree and a particular order ofinputs.If every dendritic tree can be so considered - and this is the fundamental meaningof our work on frog vision - then the whole character of a nervous system becomesexpressible in certain general terms.Let us consider the simplest case - that of a sheet array of neurons, each with anarbor that extends in great overlap with those of its neighbors, and let all arbors be ofthe same sort, i. e., let each perform the same operation on the input. Let the synapticinput be an array of an arbitrary number of types of elements with the only stipulationbeing that each type be uniformly distributed, i. e., a particular kind of input ought tohave the same density everywhere and end in the same relative order with respect toother inputs on the dendritic trees. If the input maps the distribution of qualities in animage of the external world, for example, as rods and cones map the distribution oflight and color, then the output of the neuron sheet expresses two sorts of things. A334(XX. NEUROPHYSIOLOGY)single neuron enciphers in its firing the presence of the sort of arrangement that itsdendritic tree perceives as a positive value of the function which it is built to calculate.This response indicates that in the neighborhood of the center of the dendritic tree aparticular event occurs. Thus the arrangement of exciting events in the image of theworld is mapped into a distribution of excitements which preserves the order and dis-tances of those events. But the meaning of a point in the space given by excitementsis not simple. For the nervous array, any point in the image has two meanings. First,that it is or is not in the neighborhood of an exciting event and second, that it has aparticular position in space. The first meaning is embodied in the firing of neuronsthat see this point in common. The second is embodied in the center of a single dendritictree. Thus, the local properties of a representation taken by a neuron are not to beextended. No continuum need exist, and in general does not exist, between the localfunction given by one dendritic tree and the distribution in space given by the order ofexcited neurons.This variety of what is called, I believe, the discrete manifold has spatial propertiesthat are different from those that can be obtained from a continuous manifold. Notably,regions and operations can be connected arbitrarily without having to worry aboutwhat to do with the in-between, which is a bother with a continuum. Thus one constructshierarchical layers of neurons.This report is very short, but represents much of the substance of a longer paperthat is in preparation.J. Y. LettvinB. OLFACTIONAfter R. C. Gesteland completed his thesis, we decided to plan the work on smellfor effortless recording over a long term, since with this sensory modality, more thanwith any other, secular variations of the response to stimulus, early fatigue, and enduringblock from overstimulation cause difficulties in recording which, however convincingthe pictures may be to an experimenter, obscure the lucid and compelling details fromthe casual observer. That problem, far from being confined to our work alone, is nativeto the whole field of nervous physiology, and plagues alike those who penetrate the brainand those who specialize in the peripheral nervous system. All find it troubling to sepa-rate the signals from different nervous fibers that are seen commonly through the sameelectrode, and some have even resorted to computer analysis. It is not unusual to findthat what might evade the eye is discovered readily by digital manipulation, given enoughwords and time. But there is a simple pleasure in coupling immediately and discrimi-natingly to raw events. It is also cheaper.If several axons are being recorded at the same time through one electrode, their335(XX. NEUROPHYSIOLOGY)impulses may be distinguished not only by height but by shape. In unmyelinated fibersthe impulse may be as long as 5-7 msec, may be monophasic, diphasic or triphasic(determined by the degree of blocking of the fibers by the electrode), and may be of eitherpolarity or sequence of polarities (determined by the local boundary conditions). It isnever hard to separate one fiber from another if the time base is fast enough to allowresolution of shape. But the rate of firing of the several units rarely exceeds 10 persecond, and then only with a strong stimulus. Recording events so widely spaced onfast-moving paper or film is not only wasteful but also fatiguing to read later. Becauseall of the impulses lie within essentially the same frequency band, filtering to improvethe signal-to-noise ratio leads to making the transients look more alike and washes outsmall differences that may be useful in separation. The best strategy that we have foundis to record from the nerve broad bandwidth, and to trigger an electronic switch fromsignals of a particular polarity which exceed the peak-to-peak noise. The electronicswitch couples the signal into the recording system for a prechosen interval, say,3 msec, and then decouples the signal from the record. At the same time as this"window" filter is set off, the same trigger starts a ramp function of the same lengthas the window. The ramp is added to the time base, so that the record, going on asslow a time base as one wishes, exhibits transient dilatations of the time base to resolvethe shape, as well as the height, of the transient. The results are very elegant. Thecircuit is a simple modification of a commercial instrument. This circuit makespossible meaningful recording from a mixed group of neurons.J. Y. Lettvin, R. C. Gesteland336

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