Contains reports on two research projects.Bell Telephone Laboratories, IncorporatedNational Institutes of HealthTeagle Foundation, IncorporatedUnited States Air Force, Aeronautical Systems Division (Contract AF33(616)-7783

Axelrod, F. S.

Brown, J. E., III

Rojas, J. A.

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XVI. NEUROPHYSIOLOGY*W. S. McCulloch M. C. Goodall L. M. MendellM. A. Arbib W. L. Kilmer N. M. OnestoF. S. Axelrod K. Kornacker W. H. PittsM. Blum J. Y. Lettvin J. A. RojasJ. E. Brown Diane Major A. TaubR. C. Gesteland P. D. WallA. THE EFFECT OF PENTOBARBITAL ON THE VISUAL SYSTEMOF RATSThe optic nerves of albino rats anesthetized with sodium pentobarbital (50 mg/kg)were exposed by removing the cerebrum lying over the nerves by suction. In such apreparation, the circulation in the retina and optic nerve remains intact. The duraand nerve sheath were removed from the nerve between the optic foramen and theoptic chiasm and single units were recorded by means of metal-filled glass micro-pipettes, plated with platinum black. l Single units can be stably recorded for onehour and longer; moreover, units recorded in sequence along the track of the elec-trode can be recovered upon withdrawal of the electrode in the reverse sequence.In such a preparation under pentobarbital the most striking activity recorded is asynchronous, spontaneous bursting of most of the active units at approximately 15 cps(Figs. XVI-1 and XVI-2). Almost all such units respond with a burst of spikes to the"off" of the general illumination, and are desynchronized when the general illuminationis turned on (Fig. XVI-2). This bursting "off" unit activity is quite well synchronizedthrough the nerve; a 5-micron KCI pipette, placed on the surface of the nerve, recordsa periodic potential of approximately 15-cps frequency (Fig. XVI-3).The bursting "off" unit activity is not present in the optic nerve axons of an animalprepared without any barbiturate; these animals were prepared under ether anesthesia.A midcollicular section was performed, followed by removal by suction of the cerebrumoverlying the optic nerve. If the optic nerve in such an unanesthetized animal is crushedclose to the optic chiasm and records taken distal to the crush, no such bursting activityis seen. This suggests that the bursting activity is not due to suppression of some effer-ent activity by the barbiturate. Furthermore, an electrode records many more units inthe unanesthetized animal, many of which are "on" units. If the sequence and number ofunits along an electrode track is noted and Nembutal administered, as the level of anes-thesia deepens and the electrode is withdrawn, the nerve is found to be relatively muchmore quiet, with groups of bursting "off" units not before observed now being recorded,which have quiet regions between them. Conversely, as the level of anesthesia lightens,*This work was supported in part by Bell Telephone Laboratories, Inc.; TheTeagle Foundation, Inc.; the National Institutes of Health (Grant NB-01865-05 andGrant MH-04737-02); and in part by the U. S. Air Force (Aeronautical Systems Division)under Contract AF33(616)-7783.QPR No. 69 239Fig. XVI- 1.Fig. XVI-2.A single unit of the "bursting off unit" varietyrecorded in the optic nerve of an albino ratunder pentobarbital. Time marker: 50 persecond.Several bursting units recorded in the opticnerve of an albino rat under pentobarbital.The background illumination was turned onin the middle of the sweep and off at the end.Time marker: 2 per second.Fig. XVI-3. Slow potentials recorded with a gross electrodefrom the surface of the optic nerve of an albinorat under pentobarbital. Time marker: 4 persecond.QPR No. 69 240(XVI. NEUROPHYSIOLOGY)the bursting activity diminishes and types of units other than the bursting "off" unitsare recorded.This bursting "off" unit activity was also seen in albino rats under allobarbitone(Dial, Ciba), and in both albino and Long-Evans hooded rats under pentobarbital withthe recordings taken stereotaxically with the same type of low-impedance electrodes.J. E. Brown, J. A. RojasReferences1. R. C. Gesteland, B. Howland, J. Y. Lettvin, and W. H. Pitts, Comments onmicroelectrodes, Proc. IRE 47, 1856 (1959).B. SINGLE-UNIT RESPONSES IN THE CEREBELLUM OF THE FROGThe cerebellum of the frog is a bean-shaped organ lying on the dorsal side of thebrain between the medulla and the tectal lobes. The largest nerve-fiber bundles enteringthe cerebellum are the (dorsal) spinal tract and the vestibular tract. Small tractscourse in from nerves IV and V, from the tectum, and from sundry nuclei in the medulla.The histological structure of the organ upon which these fiber tracts of different sensorymodalities converge is similar to, but less complex than, that of the mammal. That is,according to the scanty and sketchy anatomy that we find (in the frog) there are the threedistinct layers - the molecular, the granular, and the Purkinje cell layers - but theirarrangement and interconnection is less elaborate than in the mammal.1,2The present study attempts to reveal through microelectrode recording how eachmodality is handled separately and in combination by short-term responses in cells ofthe cerebellum. The recording was done with metal-filled, platinum-plated, glass elec-trodes on curarized (in several cases, uncurarized) frogs (R. pipiens). I distinguishedthe stimuli applied to the frog mainly by general qualitative differences.In harmony with the nature of the stimuli, this report is a qualitative description ofthe behavior of cerebellar cells in the frog. This description is not exhaustive and dealsonly with those cells in which the response was a clear-cut change in activity. It willbe presented as a set of categories representing the nature of the applied stimuli -vestibular, mechanical, visual, and combinations of these three.Some of the vestibular organs are simultaneously stimulated by a rotation of the frogabout an axis inclined to the horizontal. Cells that respond to this mode of stimulationare of the following types:(i) One kind has a periodic resting rate, responds to rotation both clockwise andanticlockwise with a continuous barrage, the frequency of which depends on the velocityof rotation. These resting rates change with changes in the position of the head.(ii) Another kind usually has an aperiodic, bursty, resting rate and responds toQPR No. 69 241(XVI. NEUROPHYSIOLOGY)rotation in one direction with a burst whose frequency depends on the magnitude of theacceleration. It is inhibited by, or responds only weakly to, a rotation in the other direc-tion. Such a cell shows a rapid adaptation to successive rotatory (back and forth) stim-uli. It usually does not show nicely periodic changes in resting rate with changes inposition of the head; although, in several cases, a change in position did produce aquickening of the rate (Fig. XVI-4).(iii) Another kind is (a) silent and responds to a rotation in one direction withan abrupt burst of five or more spikes whose frequency is proportional to the rate ofchange of acceleration, or (b) is silent and responds with a spike or two at the end ofrotation. Both (a) and (b) accommodate to a second stimulus presented with a period of10 seconds.In all of the above-mentioned cells possessing a resting rate, that resting rate isdepressed after a response but slowly returns after a period of at least 10 seconds(often 1 minute). The length of this period depends on the strength and the durationof the stimulus.Mechanical stimulation is performed on the limbs, and to a lesser extent on otherparts of the body - neck, back, snout, eye muscles, cornea. Cells that respond tothis mode of stimulation are of the following types:(i) One has usually an aperiodic resting rate, responds with a burst to changesin limb position, and rapidly and completely adapts to a second stimulus for a periodof at least 10 seconds. These cells are sensitive to at least one and perhaps severalmuscles acting about a particular joint in the limb, and often will respond to the samestimulus in both left and right limbs (Fig. XVI-5).(ii) Another has a periodic resting rate and responds with a burst to any one ofthe following stimuli, the choice depending on the cell: Pressing on the limb pads (ofsometimes one, two, or all four limbs), pressing on the eye muscles, and blowing andbrushing on the cornea and various parts of the skin. These stimuli depress the peri-odic resting rate after a response.(iii) A third is silent and gives a periodic response whose frequency is pro-portional to the amount of bend of a particular joint in one limb. These responses arenonadaptive and may reach a high firing rate of several hundred spikes per second, andmaintain this rate for as long as the joint is bent (Fig. XVI-6).The only other sensory modality seen thus far to affect some cells of the frog cere-bellum is vision. These cells have an aperiodic resting rate and respond with an abruptburst to the movement of an object (for example, a hand) within the visual field of aneye. They adapt after a single stimulus, and will not respond again to this stimulusfor at least 15 seconds. They thus have the same properties as the 'newness' neuronsseen by Lettvin and others in the optic tectum. 3Interactions between the various modalities occur in the cells described above.QPR No. 69 242,1ti iiFig. XVI-4. Vestibular type ii cell. Onset of stimulus indicated byan arrow beneath the trace. Spike height ~1.5 mv.a. resting rate (head in normal position).b. rotation 900 counterclockwise.c. resting rate in new position.d. rotation 900 clockwise.e. initial resting rate.f. time base, 10/sec.II i hI I I I-4--+Fig. XVI-5. Mechanical type i cell. Spike height -2 my.a. resting rate.b. right leg picked up and put down (up anddown indicated by arrows).c. resting rate.d. left leg picked up and put down.e. time base, 10/sec.QPR No. 69 243~rrllilrlrll'llllrrllllr1llrlr~lrIe I;rllllilliillliilliIlllillili~iiilliu~lrmrrmmrmrrI LL"Ie I1 lI IIIIIIUI FII]LLIIUIIl LII j I Illii ild lll. I1111 1 ] ][I _,, l jjl ] ] I]lIllllll kUlb~*~L~......lRpml Z-' IiJ~ AJ1I.LIJ IL,1~ItI J 4S 4 P 'j T 4aIIAg.ftI-Joe"---- -LL J A 1- . 'Fig. XVI-6. Mechanical type iii cell.- jSpike height -1 my. Fig. XVI-7.Part I. Extension about ankle joint with knee joint in thenormal position.a. resting rate.b.-d. increasing extension about joint.e. maximal extension.f. resting rate.g. time base, 10/sec.Part II. Extension about ankle joint with a fixed flexionabout knee joint.a. resting rate.b. increasing extension about ankle joint (increasein the same steps as in Part I. b-d).e. maximal extension.f. resting rate.g. time base, 10/sec.Interaction type a cell.Spike height -1 my.a. resting rate (head innormal position).b. resting rate (headrotated 90* clockwise).c. left toe pad pressedon four successivetimes.d. left toe pad pressedon twice (note depres-sion of the restingrate).e. resting rate (headposition as in b).f. time base, 10/sec......... .1I*(I*-~I*~r~~?; ~IPLCItllpll~~ 11**::.1-JI".I I.! L- - 1 -- -L. I J- L!(XVI. NEUROPHYSIOLOGY)These cells behave as mixtures of the following kinds:(a) Vestibular 1 and Mechanical 2. These cells have a periodic resting rate andwill respond to rotation and change their resting rate with changes in the position ofthe head, will respond, for example, with a burst to pressing on left or right toe pad,and will have their resting rate depressed immediately thereafter (Fig. XVI-7). Similarresponses are elicited in other cells with other mechanical stimuli.(b) Vestibular 2 and Mechanical 1. These cells have an aperiodic resting rate andwill respond with a burst to either rotation or movement of one or several limbs,and will have their resting rate depressed immediately thereafter.(c) Vestibular 2 and Visual. These behave as those in (b), except that vision ratherthan mechanical stimulation causes response. Visual responses have been seen in onlythis type of cell.No attempt has yet been made at strict anatomical localization of the above-mentionedgroups of cells with respect to the layers of the cerebellum. Physiologically, inpenetrating the dorsal surface of the cerebellum, the electrode, inclined caudally at avery slight angle to the vertical, encounters three distinct layers consisting of the fol-lowing groups of cells:(i) vestibular 2, vestibular 3, mechanical 1, visual(ii) vestibular 1, mechanical 2(iii) mechanical 3.The time constants of the cells in these three layers are also appreciably different.The height of the potentials recorded in the first layer is invariably greater than thatof those in the other two, and the cells in this layer are electrically closely packed.These cells are probably the Purkinje cells, which are the largest (~10 4 in diameter)and the most closely packed cells in the cerebellum.With the exception of vestibular 3 responses, the short-term response pattern ofthe cerebellar cells is not appreciably different from that found in the fiber tractsentering the cerebellum. In fact, the response in mechanical 3 seems no differentfrom what would be expected in a tendon-stretch receptor itself, unless, indeed, thisresponse is combinatorial with other stretch receptors in the limb (as is perhaps thecase in Fig. XVI-6). The differences are found in the combination of the responses ofvarious modalities and in that of the responses from several limbs within a single cell.The most patent use to the frog of the short-term responses of cerebellar cells isin the rapid control of efferents to muscle. For example, Granit, Holmgren, andMerton 4 have shown that in the cat the cerebellum in some way regulates the proportionof the two routes of muscle excitation, a and y, in use at any time. That there is alarge representation of the y efferents in the cerebellum is seen in the large decreasein cellular activity in layer ii when a frog is curarized. (Curare knocks out musclespindle activity.) The proportion of the two routes in use in a given muscle at any timeQPR No. 69 245(XVI. NEUROPHYSIOLOG Y)is very likely dependent on vestibular, dermal, visual, and other muscular activity.The nature of these short-term responses allows the cerebellum to perform just sucha regulation.The long-term responses of the cerebellar cells consist in the setting and modulationof the complex resting rates (not strictly aperiodic but almost cyclic in the repetitionof a bursting pattern) of those cells by previous vestibular, mechanical, and perhapsvisual stimuli. These kinds of responses are suited to making the cerebellum in partan organ that can 'remember' previous trajectories of a frog in its milieu, and that canplot intended trajectories of the animal. This bit of speculation will be the object offurther study on the cerebellum of the frog.F. S. AxelrodReferences1. O. Larsell, The cerebellum of the frog, J. Comp. Neurol. 36, 89-113 (1923).2. P. Glees, C. Pearson, and A. G. Smith, Synapses on Purkinje cells of the frog,Quart. J. Exptl. Physiol. 43, 52-61 (1958).3. J. Y. Lettvin, H. R. Maturana, W. H. Pitts, and W. S. McCulloch, Two remarkson the visual system of the frog, in Sensory Communication, edited by W. A. Rosenblith(The M. I. T. Press, Cambridge, Mass., and John Wiley and Sons, Inc., New York andLondon, 1961).4. R. Granit, B. Holmgren, and P. A. Merton, The two routes for excitation ofmuscle and their subservience to the cerebellum, J. Physiol. 130, 213-225 (1955).QPR No. 69 246

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