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Comments on Structure-Function Relationships in the Peripheral Vestibular System
COMMENTS ON STRUCTURE-FUNCTION RELATIONSHIPS IN THE PERIPHERAL VESTIBULAR SYSTEM
R. Llinas and D. E. Hillman Division of Neurobiology Dep artment of Physiology & Biophysics Department University of Iowa Iowa City 52242
It is a pleasure to chair this session on Auditory leasure is greater and Vestibular Response. The ppleasure art with the since the session deals at least in ppart roperties of the vestibular system, one functional pproperties of the most rewarding subjects of study in neurors pprerebiology today. As is evident from the pape papers sented at this meeting, the vestibular system, as indee d more than an viewed by modern research, is indeed apparatus to keep one's head straight with respect to one's shoulders!
serves as the transducing mechanism. The second hypothesis views the transduction system as another we ll known mechanoreceptor pproperties roperties form of the well riphe ral recentor r ecentor cells. of other pe peripheral
s tron g l y supported the latte Our own research has strongly latterr se ries of transmission ultrastruchypothesis. A series studies (5) , as well we ll as scanning s canning electron e lectron tural studies(5), microscopy(7) , has demonstrated rather revealing revea ling morp hology of the rece~tor rece ~ tor cell: features of the morphology The basic findings regarding orientation of the re spect to the stereocilia in the t he kinocilium with respect rece p tor cell were we re found to be the same top of the receptor lished by Flock & Wersall(4). We r sall(4). f ew as that pub published In a few words, wo rds, in utricular and saccular sacc ular receptors receptor s the l ocated in true cilium, called the kinocilium, is located such a strategic position posit ion (the pe ri p hery of the periphery ciliary tuft) that movements movement s of the ciliary system IVould result in a maximum bending be nding of this particu,.,ould tion. lar cilium in a given direc direction. This hypothesis Flock(3) , who also proposed p roposed was first proposed bv Flock(3), s liding relationship with that stereocilia had a sliding each other and that their kinocilium was always Mo re reoriented in the same direction (Fig. 1). More Hil lman & Lewis(7) have cently, Hillman(5) and Hillman sacculu s the kinocilium has a shown that in the sacculus filament s to matchhead-like ending bound by small filaments adjacent stereocilia (in conflict with the sliding pproperty roperty proposed p roposed by Flock). Since S ince it has been \·..hich shOlm that the kinocilium is the only cilium \·.'hich is not resting over the cuticular pplate late (Fig. 2) b ut rather that it has a soft s oft base provided p rovid ed by the but pplasma la sma membrane exclusively, exc lu s ive l y , the follo wing h:'potheh :'pothefollowing p ro posed. As shown in Fig. 2, during sis has been pro~osed. t he kinocilium behaves movement of the ciliary tuft the force·-transmi tting column c o lumn which wh ich tends to de·· de ·· as a force·-transmitting form the plasma p lasma membrane at its base. This deforma tion of the membrane is then assumed to produce p roduc e mation an ionic conductance change in a manner similar rec eptor systems such as the Pacinian Pac inian to other receptor corpuscle (8) or st r etch receptor(14). recep tor(14). On the other o th er corpuscle(8) stretch hand , movements of the tuft in the opposite hand, o~posite direct e nd to tion (i.e. away from the kinocilium) would tend r e lease this ppressure res su re and allow the t he plasma p la sma membrane release t o a more relaxed state where whe re the pphysical hysical to come to deformation would wou ld be least l east and thus the resting re st in g decreased (5 ,7) . A membrane conductance would be decreased{5,7). schematic representation of this hypothesis is \-Ihi le the pictures pict ures shown here he re shown in Fig. 2a, c. \"Ihile are representative rep resentative only on ly of the utricular and saccu·· saccu-· recep tor areas, similar simi lar studies done in the lar receptor sys t em strongly s trongly suggest that the semicircular canal system
The morphological complexity of the peripheral wea lth in the vesvestibular system and the fiber wealth po rtion of the VIIIth nerve may be taken tibular portion s ystem competes comp etes in complexity as evidence that this system co unterpa rts. In comcomwith its visual or auditory counterparts. paring these three sensory modalities (i.e. visual, auditory and vestibular), it is interesting to note that while in the visual and auditory systems such pproperties rope rties as stimulus directionality are construed inte g ration, in the vestibular by central neuronal integration, rop erty of the system directionality is an actual p property receptor itself.
riphe ral vestibular Anatomical features of the pe peripheral wh ich relate to directionality system which That the vestibular system (both utricular-saccular comp lexes and semicircular canals) responds respond s to discomplexes p lacement in space in a specified spec ified direction has placement recentl y , been known for a long time (10) . More recently, & wersall(ll) \~ersall (11) and Flock(3) Flock (3) demonstrated Lowenstein & that the directionality of the t he responses res ponses seen in \vas pprobably robab ly related to the the vestibular nerve was location of the kinocilium on the surface of the receptor cells (see Fig. 2e). on of the disThe actual mechanism of transducti transduction p lacement or bending of cilia into transmitter rer eplacement recepto r neuron has been a subject of of lease by the receptor year s. Although Altho ugh a final condiscussion in recent years. reach ed , it is worthwhile to clusion has not been reached, t wo possibilities. Via the hair cells, the mention two vestibular system transduces displacement (or e lectrostat ic charges which shearing forces) into electrostatic polarize the cilia in a longitudinal sense; this effect is thought to generate a current flow across rece p tor cell as the path current moves from the receptor sys t em to the other. This one end of the dipole system hypothesis regards the system as roughly analogous y stem ,,,here ,,,he re a piezo to a carbon microphonic ss~'stem piezo-t ype of pro~erty p ro ~ erty of o f the receptor recep tor cell electric type
-...,---;----;------,;-----,-- - -----_. -.. ----- .. -=----;------;------,;----,-------.-,,---,,S uperio r numbers refer to similarly similarl y numbered references at the end of this th is Superior
180
~ ape r . ~aper.
same type of mechanism is operant in those receptors. The semicircular canal receptor system To our surprise it has been found that, opposed to the views of Steinhausen(15) and Dohlman(1,2) , the cupular system in the semicircular canals behaves more like a diaphragm which is peripherally attached to the inner surface of the canal (6) rather than the 'sliding door' hypothesis put forth by Dohlman(2). Furthermore, study of displacement of the cupular diaphragm following rotation of frog isolated head indicates that the actual physical displacement of this membrane is not uniform throughout its area. In fact, at very low angular accelerations the central most part of the diaphragm (which is thinner) is the first to show displacement. As higher accelerations are applied, the deformation invades the more peripheral part of the diaphragm which is thicker and has a slower visco-elastic time constant and probabl y responds in thus is activated later and probably a slower fashion as well(6). This type of cupular arrangement in the semicircular canals suggests, from a purely morphological standpoint, that the receptors which are located near the peripheral ends of the crista would tend to be activated more slowly and the activity to last for a longer period than those in the center. Thus a distribution of the sensitivity of the receptor system would be rather broad and, given almost any form of angular acceleration, the information regarding cupular displacement could be, for most accelerations, within the linear portion of a particular group of receptor cells. This mechanism may, in fact, go a long way in explaining the rather enormous range of accelerations that the vestibular system appears able to handle. Thus, as calculated by Oman & Young (13) , the minimal displacement which the cupular system and the semicircular canals would be able to detect would be in the vicinity of 10 millimicrons for an acceleration level of 0.lo/sec 2 (assuming Dohlman's p robably be 3 hypothesis) while the maximum would probably microns for a 30 o/sec 2 acceleration (high accelerations are probably present, especially followrap id energy exchange; e.g. a blow to a boxer's ing rapid jaw or an abrupt stop). These estimates are based on the calculation of the moment of inertia of the endolymph in the canal which yields a pressure drop of 10- 2 dyne/cm 2 across the cupula for an acceleration of 0.lo/sec 2 . The calculations assume, however, that the cupula is an homogeneous barrier, rather than capable of the differential deformation hypothesized by Hillman(6).
O'Leary and Honrubia have in fact demonstrated by recording from single fibers in the semicircular canal system of elasmobranchs that fibers coming from different parts of the ampullar region have different functional properties. Thus, as expected from anatomical findings,the fibers which innervate receptors near the center of the diaphragm have rather low threshold, short time course of discharge, and accommodate rather quickly fol-lowing an impulse stimulus. On the other hand, those fibers innervating receptors in the more peripheral part of the cupular region have a higher threshold, a longer time course of response, and a slightly more sustained firing which outlasts the impulse stimulus (Fig. 3). The point of bringing this factual information to this particular meeting relates to the general topic of relevant parameters of study when considering systems as complex as the vestibular organ. Apparent from the above results is the fact that the vestibular system, even at its peripheral level, is much more complex than previously thought. More to the point, the level of sophistication implied by the basic morphological and functional properties of the system suggests a unsusp ecrichness of sensory encoding previously unsuspected. From a purely teleological point of view, it appears that the sense of position of one's body with respect to universals is central to the generation of an 'internal image of reality' (9). Since one of the most important systems in such internalization is the vestibular system, the role of this system in the normal development of the 'image of the perceived world' must be kept in mind when considering vestibular physiology in a more holistic sense. The spatial disorientation of individuals subject to complex rotations or to incongruous vestibular and visual stimuli (Coriolis effect) is a good example of the rather central role of the vestibular system in the general organerception. ization of pperception. Similarly, we have heard from other authors today that the efferent auditory system (and perhaps the efferent vestibular system) may be extremely important in regulating gain in these receptors. Probably of even higher importance may be the fact that through the use of these pathwa ~' s the nervous system may be able to efferent pathwa~'s differentiate active stimulation (arising from muscular movements) from passive stimulation (arising from stimuli generated in the surrounding world). In any event, we must agree that the more interesting questions in our field are those which relate to global understanding, even if the level of explanation at this time provides only for general direction or working hypotheses. Acknowledgement
Although it is correct that Hillman's hypothesis is based primarily on anatomical data, a similar conclusion has been independently reached by O'Leary & Honrubia(12) in a recent set of electrophysiological studies in the isolated vestibular system. The experiments demonstrate the differences in sensitivity in the central and peripheral cup ular system and receptors of the semicircular cupular are in total agreement with the idea that this receptor system is organized as hypothesized above.
This research was supported in part by USPHS grant NS09916 from NINDS. The authors would like to thank Drs. O'Leary and Honrubia for allowing us to use their results to illustrate some of the points of vestibular physiology.
181
REFERENCES (1)
Dohlman, G.F., "Some aspects of the mechanism of vestibular hair cell stimulation," CONFIN. NEUROL., NEURaL., Vol 20 (1960), 169-180.
(2) Dohlman, G.F., "The shape and function of the cupula,1I J. LARYNG. OTOL., Vol 83 (1969), cupula," 43-53. (3) Flock, A., "Structure " St ructure of the macula utriculi with special reference to directional interplay p lay of sensory responses as revealed reveal e d by morpho logical polarization," J. CELL BIOL. , morphological Vol 22 (1964), 413-431.
\'ie rsall, "A study of the (4) Flock, A. and J. \i]ersiHl, orientation o ri e ntation of o f the sensory hairs of the receptor cells in the lateral line organ of e r ence to t o the function fish, with special ref reference recep tors," J. CELL BIOL., Vol 15 of the receptors," 1 9 -27. (1962), 19-27.
(13) Oman, C.M. and L.R. Young, "Physiological range of pressure difference and cupula deflections in the human semicircular canal: Theoretical considerations," PROGRESS IN BRAIN RESEARCH, Vol 37 (1972), 529-539. (14) Ottoson, D. and G.M. Shepherd, "Receptor potentials and impulse generation in the isolated spindle during controlled extension," SYMP . QUANT. BIOL., Vol 30 COLD SPRING HARE. SYMP. (1965), 105-114. (15) Steinhausen, W., "Ueber die direkte beobachtung der sinnesendstellen des inneren ohres," VERHANDL. DEUTSCHE ZOOL. GES., Vol vol 36, Suppl 8 5-91. 7 (1934), 85-91.
ultra st ructural findings (5) Hillman, D.E., "New ultrastructural ciliary apparatus and regarding a vestibular ciliarv ible functional significance," BRAIN its poss possible RES., Vol 13 (1969), (1 969) , 407-412. 40 7-412. "Obse rvati ons on morphological (6) Hillman, D.E., "Observations mechani ca l pproperties rope rties of the features and mechanical pe ri phera l vestibular receptor re cepto r system sys t em in the peripheral Vol. 37 frog," PROGRESS IN BRAIN RESEARCH, Vo1. (1 972) , 69-75. 69 -75. (1972), Hi llman, D.E. and E.R. Lewis, "Morphological "Morpho l ogical (7) Hillman, linkag e in otolithic basis for a mechanical linkage recep t o r transduction in the frog," SCIENCE, SC IENCE, receptor Vol 174 (1971), 416-419. (8)
"P roc esses of o f excitation and ILYINSKI, O.B., "Processes inhibition in single mechanoreceptors (Pacin ian corpuscles) ," NATURE, Vol 208 (Pacinian (1 965) , 351-353. (1965),
(9) Llinas, R., "The significance of form in r ess) . neuronal function," LA RECHERCHE (in ppress).
O. and A. Sand, "The mechanism (1 0) Lowenstein, o. (10) semicircular canal. can al. A study of o f the of the semicircular responses of single-fibre prepa preparations rations to accele rations and to rotation r otation at conangular accelerations SOC . B, Vol 129 12 9 stant speed," PROC. ROYAL SOC. 256 - 275. ( 1 940) , 256-275. (1940), (11 ) Lowenstein, Lowenste in, o. (11) O. and J. vlersal1, \·iersall, "A functional interp r eta ti on of the electron microscopic microscop ic interpretation structure of the sensory hairs in the cristae c lavata in terms of of the elasmobranch Raja clavata directional sensitivity," NATURE, Vol 184 1807-1808 . (1959), 1807-1808. 0 ' Leary, D.P. D. P. and V. Honrubia, Hon rubia, "Linear systems (12) O'Leary, anal ys is of semicircular canal c anal afferent reanalysis o f the ray. sponses in the isolated labyrinth of PROC. IV INTERNAT. BIOPHYS. CONGR., Moscow (1972), E-XVIa5/7.
182
i g . 1. Scanning electron micrographs of receptor recep tor cell ciliary c iliary comnlexes comn lexes of o f the three major vestibular ig. Kinoc iliurn, k; stereocilia, s: s; receptor recep tor cell, rc: rc; suoporting cells, sc. eceptor organs. Kinociliurn,k: A: Long tereoc ilia and kinocilia project from receptor re cept o r cells of the crista ampullaris. amp ullaris. No t e that besides bes ides a tereocilia Note kinoci l ia as seen in the ciliary tuft (*). (*) . umber of short stereocilia, other very long ones accompany the kinocilia l o ng, single kinociliurn pprojects rojects from a ciliary tuft without long lon g stereocilia. This n the foreground a long, ri phe r y of the receptor r ecept o r surface. s urface. B: B : Ciliary tuft extending from a saccular receprece p ype occurs at the pe periphery ce ll. Not kinoci li urn with its match-like match- l ike head. C: C : Ciliary tuft fro m a utricular receptor r ecep tor cell. or cell. Notee the kinociliurn from he stereocilia s t e re oc ilia are usually usua ll y much shorter than the saccular sa ccular type and reach r e ach the apical a pical end of o f the kinocilia nly in a specific s pec ific zone.
183
5s
I
I
(/ y.
e - like action of ciliary apparatus. cutic l e. Fig. 2. Demonstration of plunger plunger-like C, cuticle; N, notch in cuticle. a and b: A force toward the kinocilium (K) causes kinociliar base to indent into receptor cell (RC) and o roduces a deformation of the plasma p l asma membrane at base of kinocilium. c and d: Horizontal motion in opnooroduces ~ite direction raises kinocilium and results in release re l ease of tension on the plasma membrane at base of kinocilium . ci l iary anparatus ",ith attachment of the kinocilium to adjacent stereocilia kinocilium. e: Diagram shows ciliary (S). The stereocilia stand over the cuticle and the kinocilium over the cuticular notch.
-
.. "-. ~"""'-"""'.,"""",",.:...,-."":~':~:;;::'~'::~. ~ """'--"''"'''''" ,.:...,-."'':~':~:;;::'~'::~. ~.', ~", .- '.'
~
Fig. 3. Variations in linear system impulse response characteristics from the semicircular canal. Impulse res ponse estimates are shown from 8 different horizontal semicircular canal afferents from the isolated response roductus). res p onses , obtained obtalned by cross-correlating cross - correlatlng left labyrinth of the guitar fish (Rhinobatos pproductus). The responses, inters p ike intervals with pseudo p seudo random binary (whi te ~ise) inputs of amplitude amp litude = .::':1000/sec clock interspike (white~ise) ~100o/sec2L and clockp u l se = 92.0 msec, msec , are ordered in the figure to illustrate variations varia t ions in response decay times. times . pulse In general, responses with slower decay times (upper in the figure) were observed from sub-bundles sub - bundles located on the rostral side of the horizontal canal nerve and resoonses res oonses with faster decay times (lower in the figure) were observed from sub-bundles sub - bundles located centrally in the nerve. (From O'Leary O 'Leary and Honrubia)
184
R. Llinas and D. E. Hillman Division of Neurobiology Dep artment of Physiology & Biophysics Department University of Iowa Iowa City 52242
It is a pleasure to chair this session on Auditory leasure is greater and Vestibular Response. The ppleasure art with the since the session deals at least in ppart roperties of the vestibular system, one functional pproperties of the most rewarding subjects of study in neurors pprerebiology today. As is evident from the pape papers sented at this meeting, the vestibular system, as indee d more than an viewed by modern research, is indeed apparatus to keep one's head straight with respect to one's shoulders!
serves as the transducing mechanism. The second hypothesis views the transduction system as another we ll known mechanoreceptor pproperties roperties form of the well riphe ral recentor r ecentor cells. of other pe peripheral
s tron g l y supported the latte Our own research has strongly latterr se ries of transmission ultrastruchypothesis. A series studies (5) , as well we ll as scanning s canning electron e lectron tural studies(5), microscopy(7) , has demonstrated rather revealing revea ling morp hology of the rece~tor rece ~ tor cell: features of the morphology The basic findings regarding orientation of the re spect to the stereocilia in the t he kinocilium with respect rece p tor cell were we re found to be the same top of the receptor lished by Flock & Wersall(4). We r sall(4). f ew as that pub published In a few words, wo rds, in utricular and saccular sacc ular receptors receptor s the l ocated in true cilium, called the kinocilium, is located such a strategic position posit ion (the pe ri p hery of the periphery ciliary tuft) that movements movement s of the ciliary system IVould result in a maximum bending be nding of this particu,.,ould tion. lar cilium in a given direc direction. This hypothesis Flock(3) , who also proposed p roposed was first proposed bv Flock(3), s liding relationship with that stereocilia had a sliding each other and that their kinocilium was always Mo re reoriented in the same direction (Fig. 1). More Hil lman & Lewis(7) have cently, Hillman(5) and Hillman sacculu s the kinocilium has a shown that in the sacculus filament s to matchhead-like ending bound by small filaments adjacent stereocilia (in conflict with the sliding pproperty roperty proposed p roposed by Flock). Since S ince it has been \·..hich shOlm that the kinocilium is the only cilium \·.'hich is not resting over the cuticular pplate late (Fig. 2) b ut rather that it has a soft s oft base provided p rovid ed by the but pplasma la sma membrane exclusively, exc lu s ive l y , the follo wing h:'potheh :'pothefollowing p ro posed. As shown in Fig. 2, during sis has been pro~osed. t he kinocilium behaves movement of the ciliary tuft the force·-transmi tting column c o lumn which wh ich tends to de·· de ·· as a force·-transmitting form the plasma p lasma membrane at its base. This deforma tion of the membrane is then assumed to produce p roduc e mation an ionic conductance change in a manner similar rec eptor systems such as the Pacinian Pac inian to other receptor corpuscle (8) or st r etch receptor(14). recep tor(14). On the other o th er corpuscle(8) stretch hand , movements of the tuft in the opposite hand, o~posite direct e nd to tion (i.e. away from the kinocilium) would tend r e lease this ppressure res su re and allow the t he plasma p la sma membrane release t o a more relaxed state where whe re the pphysical hysical to come to deformation would wou ld be least l east and thus the resting re st in g decreased (5 ,7) . A membrane conductance would be decreased{5,7). schematic representation of this hypothesis is \-Ihi le the pictures pict ures shown here he re shown in Fig. 2a, c. \"Ihile are representative rep resentative only on ly of the utricular and saccu·· saccu-· recep tor areas, similar simi lar studies done in the lar receptor sys t em strongly s trongly suggest that the semicircular canal system
The morphological complexity of the peripheral wea lth in the vesvestibular system and the fiber wealth po rtion of the VIIIth nerve may be taken tibular portion s ystem competes comp etes in complexity as evidence that this system co unterpa rts. In comcomwith its visual or auditory counterparts. paring these three sensory modalities (i.e. visual, auditory and vestibular), it is interesting to note that while in the visual and auditory systems such pproperties rope rties as stimulus directionality are construed inte g ration, in the vestibular by central neuronal integration, rop erty of the system directionality is an actual p property receptor itself.
riphe ral vestibular Anatomical features of the pe peripheral wh ich relate to directionality system which That the vestibular system (both utricular-saccular comp lexes and semicircular canals) responds respond s to discomplexes p lacement in space in a specified spec ified direction has placement recentl y , been known for a long time (10) . More recently, & wersall(ll) \~ersall (11) and Flock(3) Flock (3) demonstrated Lowenstein & that the directionality of the t he responses res ponses seen in \vas pprobably robab ly related to the the vestibular nerve was location of the kinocilium on the surface of the receptor cells (see Fig. 2e). on of the disThe actual mechanism of transducti transduction p lacement or bending of cilia into transmitter rer eplacement recepto r neuron has been a subject of of lease by the receptor year s. Although Altho ugh a final condiscussion in recent years. reach ed , it is worthwhile to clusion has not been reached, t wo possibilities. Via the hair cells, the mention two vestibular system transduces displacement (or e lectrostat ic charges which shearing forces) into electrostatic polarize the cilia in a longitudinal sense; this effect is thought to generate a current flow across rece p tor cell as the path current moves from the receptor sys t em to the other. This one end of the dipole system hypothesis regards the system as roughly analogous y stem ,,,here ,,,he re a piezo to a carbon microphonic ss~'stem piezo-t ype of pro~erty p ro ~ erty of o f the receptor recep tor cell electric type
-...,---;----;------,;-----,-- - -----_. -.. ----- .. -=----;------;------,;----,-------.-,,---,,S uperio r numbers refer to similarly similarl y numbered references at the end of this th is Superior
180
~ ape r . ~aper.
same type of mechanism is operant in those receptors. The semicircular canal receptor system To our surprise it has been found that, opposed to the views of Steinhausen(15) and Dohlman(1,2) , the cupular system in the semicircular canals behaves more like a diaphragm which is peripherally attached to the inner surface of the canal (6) rather than the 'sliding door' hypothesis put forth by Dohlman(2). Furthermore, study of displacement of the cupular diaphragm following rotation of frog isolated head indicates that the actual physical displacement of this membrane is not uniform throughout its area. In fact, at very low angular accelerations the central most part of the diaphragm (which is thinner) is the first to show displacement. As higher accelerations are applied, the deformation invades the more peripheral part of the diaphragm which is thicker and has a slower visco-elastic time constant and probabl y responds in thus is activated later and probably a slower fashion as well(6). This type of cupular arrangement in the semicircular canals suggests, from a purely morphological standpoint, that the receptors which are located near the peripheral ends of the crista would tend to be activated more slowly and the activity to last for a longer period than those in the center. Thus a distribution of the sensitivity of the receptor system would be rather broad and, given almost any form of angular acceleration, the information regarding cupular displacement could be, for most accelerations, within the linear portion of a particular group of receptor cells. This mechanism may, in fact, go a long way in explaining the rather enormous range of accelerations that the vestibular system appears able to handle. Thus, as calculated by Oman & Young (13) , the minimal displacement which the cupular system and the semicircular canals would be able to detect would be in the vicinity of 10 millimicrons for an acceleration level of 0.lo/sec 2 (assuming Dohlman's p robably be 3 hypothesis) while the maximum would probably microns for a 30 o/sec 2 acceleration (high accelerations are probably present, especially followrap id energy exchange; e.g. a blow to a boxer's ing rapid jaw or an abrupt stop). These estimates are based on the calculation of the moment of inertia of the endolymph in the canal which yields a pressure drop of 10- 2 dyne/cm 2 across the cupula for an acceleration of 0.lo/sec 2 . The calculations assume, however, that the cupula is an homogeneous barrier, rather than capable of the differential deformation hypothesized by Hillman(6).
O'Leary and Honrubia have in fact demonstrated by recording from single fibers in the semicircular canal system of elasmobranchs that fibers coming from different parts of the ampullar region have different functional properties. Thus, as expected from anatomical findings,the fibers which innervate receptors near the center of the diaphragm have rather low threshold, short time course of discharge, and accommodate rather quickly fol-lowing an impulse stimulus. On the other hand, those fibers innervating receptors in the more peripheral part of the cupular region have a higher threshold, a longer time course of response, and a slightly more sustained firing which outlasts the impulse stimulus (Fig. 3). The point of bringing this factual information to this particular meeting relates to the general topic of relevant parameters of study when considering systems as complex as the vestibular organ. Apparent from the above results is the fact that the vestibular system, even at its peripheral level, is much more complex than previously thought. More to the point, the level of sophistication implied by the basic morphological and functional properties of the system suggests a unsusp ecrichness of sensory encoding previously unsuspected. From a purely teleological point of view, it appears that the sense of position of one's body with respect to universals is central to the generation of an 'internal image of reality' (9). Since one of the most important systems in such internalization is the vestibular system, the role of this system in the normal development of the 'image of the perceived world' must be kept in mind when considering vestibular physiology in a more holistic sense. The spatial disorientation of individuals subject to complex rotations or to incongruous vestibular and visual stimuli (Coriolis effect) is a good example of the rather central role of the vestibular system in the general organerception. ization of pperception. Similarly, we have heard from other authors today that the efferent auditory system (and perhaps the efferent vestibular system) may be extremely important in regulating gain in these receptors. Probably of even higher importance may be the fact that through the use of these pathwa ~' s the nervous system may be able to efferent pathwa~'s differentiate active stimulation (arising from muscular movements) from passive stimulation (arising from stimuli generated in the surrounding world). In any event, we must agree that the more interesting questions in our field are those which relate to global understanding, even if the level of explanation at this time provides only for general direction or working hypotheses. Acknowledgement
Although it is correct that Hillman's hypothesis is based primarily on anatomical data, a similar conclusion has been independently reached by O'Leary & Honrubia(12) in a recent set of electrophysiological studies in the isolated vestibular system. The experiments demonstrate the differences in sensitivity in the central and peripheral cup ular system and receptors of the semicircular cupular are in total agreement with the idea that this receptor system is organized as hypothesized above.
This research was supported in part by USPHS grant NS09916 from NINDS. The authors would like to thank Drs. O'Leary and Honrubia for allowing us to use their results to illustrate some of the points of vestibular physiology.
181
REFERENCES (1)
Dohlman, G.F., "Some aspects of the mechanism of vestibular hair cell stimulation," CONFIN. NEUROL., NEURaL., Vol 20 (1960), 169-180.
(2) Dohlman, G.F., "The shape and function of the cupula,1I J. LARYNG. OTOL., Vol 83 (1969), cupula," 43-53. (3) Flock, A., "Structure " St ructure of the macula utriculi with special reference to directional interplay p lay of sensory responses as revealed reveal e d by morpho logical polarization," J. CELL BIOL. , morphological Vol 22 (1964), 413-431.
\'ie rsall, "A study of the (4) Flock, A. and J. \i]ersiHl, orientation o ri e ntation of o f the sensory hairs of the receptor cells in the lateral line organ of e r ence to t o the function fish, with special ref reference recep tors," J. CELL BIOL., Vol 15 of the receptors," 1 9 -27. (1962), 19-27.
(13) Oman, C.M. and L.R. Young, "Physiological range of pressure difference and cupula deflections in the human semicircular canal: Theoretical considerations," PROGRESS IN BRAIN RESEARCH, Vol 37 (1972), 529-539. (14) Ottoson, D. and G.M. Shepherd, "Receptor potentials and impulse generation in the isolated spindle during controlled extension," SYMP . QUANT. BIOL., Vol 30 COLD SPRING HARE. SYMP. (1965), 105-114. (15) Steinhausen, W., "Ueber die direkte beobachtung der sinnesendstellen des inneren ohres," VERHANDL. DEUTSCHE ZOOL. GES., Vol vol 36, Suppl 8 5-91. 7 (1934), 85-91.
ultra st ructural findings (5) Hillman, D.E., "New ultrastructural ciliary apparatus and regarding a vestibular ciliarv ible functional significance," BRAIN its poss possible RES., Vol 13 (1969), (1 969) , 407-412. 40 7-412. "Obse rvati ons on morphological (6) Hillman, D.E., "Observations mechani ca l pproperties rope rties of the features and mechanical pe ri phera l vestibular receptor re cepto r system sys t em in the peripheral Vol. 37 frog," PROGRESS IN BRAIN RESEARCH, Vo1. (1 972) , 69-75. 69 -75. (1972), Hi llman, D.E. and E.R. Lewis, "Morphological "Morpho l ogical (7) Hillman, linkag e in otolithic basis for a mechanical linkage recep t o r transduction in the frog," SCIENCE, SC IENCE, receptor Vol 174 (1971), 416-419. (8)
"P roc esses of o f excitation and ILYINSKI, O.B., "Processes inhibition in single mechanoreceptors (Pacin ian corpuscles) ," NATURE, Vol 208 (Pacinian (1 965) , 351-353. (1965),
(9) Llinas, R., "The significance of form in r ess) . neuronal function," LA RECHERCHE (in ppress).
O. and A. Sand, "The mechanism (1 0) Lowenstein, o. (10) semicircular canal. can al. A study of o f the of the semicircular responses of single-fibre prepa preparations rations to accele rations and to rotation r otation at conangular accelerations SOC . B, Vol 129 12 9 stant speed," PROC. ROYAL SOC. 256 - 275. ( 1 940) , 256-275. (1940), (11 ) Lowenstein, Lowenste in, o. (11) O. and J. vlersal1, \·iersall, "A functional interp r eta ti on of the electron microscopic microscop ic interpretation structure of the sensory hairs in the cristae c lavata in terms of of the elasmobranch Raja clavata directional sensitivity," NATURE, Vol 184 1807-1808 . (1959), 1807-1808. 0 ' Leary, D.P. D. P. and V. Honrubia, Hon rubia, "Linear systems (12) O'Leary, anal ys is of semicircular canal c anal afferent reanalysis o f the ray. sponses in the isolated labyrinth of PROC. IV INTERNAT. BIOPHYS. CONGR., Moscow (1972), E-XVIa5/7.
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i g . 1. Scanning electron micrographs of receptor recep tor cell ciliary c iliary comnlexes comn lexes of o f the three major vestibular ig. Kinoc iliurn, k; stereocilia, s: s; receptor recep tor cell, rc: rc; suoporting cells, sc. eceptor organs. Kinociliurn,k: A: Long tereoc ilia and kinocilia project from receptor re cept o r cells of the crista ampullaris. amp ullaris. No t e that besides bes ides a tereocilia Note kinoci l ia as seen in the ciliary tuft (*). (*) . umber of short stereocilia, other very long ones accompany the kinocilia l o ng, single kinociliurn pprojects rojects from a ciliary tuft without long lon g stereocilia. This n the foreground a long, ri phe r y of the receptor r ecept o r surface. s urface. B: B : Ciliary tuft extending from a saccular receprece p ype occurs at the pe periphery ce ll. Not kinoci li urn with its match-like match- l ike head. C: C : Ciliary tuft fro m a utricular receptor r ecep tor cell. or cell. Notee the kinociliurn from he stereocilia s t e re oc ilia are usually usua ll y much shorter than the saccular sa ccular type and reach r e ach the apical a pical end of o f the kinocilia nly in a specific s pec ific zone.
183
5s
I
I
(/ y.
e - like action of ciliary apparatus. cutic l e. Fig. 2. Demonstration of plunger plunger-like C, cuticle; N, notch in cuticle. a and b: A force toward the kinocilium (K) causes kinociliar base to indent into receptor cell (RC) and o roduces a deformation of the plasma p l asma membrane at base of kinocilium. c and d: Horizontal motion in opnooroduces ~ite direction raises kinocilium and results in release re l ease of tension on the plasma membrane at base of kinocilium . ci l iary anparatus ",ith attachment of the kinocilium to adjacent stereocilia kinocilium. e: Diagram shows ciliary (S). The stereocilia stand over the cuticle and the kinocilium over the cuticular notch.
-
.. "-. ~"""'-"""'.,"""",",.:...,-."":~':~:;;::'~'::~. ~ """'--"''"'''''" ,.:...,-."'':~':~:;;::'~'::~. ~.', ~", .- '.'
~
Fig. 3. Variations in linear system impulse response characteristics from the semicircular canal. Impulse res ponse estimates are shown from 8 different horizontal semicircular canal afferents from the isolated response roductus). res p onses , obtained obtalned by cross-correlating cross - correlatlng left labyrinth of the guitar fish (Rhinobatos pproductus). The responses, inters p ike intervals with pseudo p seudo random binary (whi te ~ise) inputs of amplitude amp litude = .::':1000/sec clock interspike (white~ise) ~100o/sec2L and clockp u l se = 92.0 msec, msec , are ordered in the figure to illustrate variations varia t ions in response decay times. times . pulse In general, responses with slower decay times (upper in the figure) were observed from sub-bundles sub - bundles located on the rostral side of the horizontal canal nerve and resoonses res oonses with faster decay times (lower in the figure) were observed from sub-bundles sub - bundles located centrally in the nerve. (From O'Leary O 'Leary and Honrubia)
184