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1 Research in Vestibular Science Vol. 8, No. 2, December 2009 Review ISSN 전정구심성및원심성신경의전기생리학적반응 성균관대학교의과대학강북삼성병원이비인후과 반재호 Electrophysiologic Response of the Vestibular Afferents and Efferents Jae Ho Ban, MD, PhD Department of Otorhinolaryngology-Head and Neck Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea 서 론 이루어져있다. 인체의전정계는평형을유지하는역할을담당하며말초전정계와중추전정계로구성된다. 말초전정계는머리의움직임을감지하여전정신경을통해전정핵과소뇌로전달하며중추전정계는말초전정계에서들어온정보를시각, 체성감각, 자율신경계의정보와통합하여머리의위치와움직임, 중력의방향을인식하여시선을고정하고안정된머리와몸의자세를유지하는역할을한다. 이때말초전정기관과중추전정계사이에서정보를교류할수있도록연결해주는역할을하는것이전정신경이다. 전정신경은말초전정의감각상피세포에서감지된신호를뇌간의전정신경핵으로전달하는구심성전정신경이주가되고, 외측전정신경핵의전방내측과외향신경핵의외측, 내측전정핵의아래에서기시하여구심성전정신경을따라말초전정기관의각부분에분포하는원심성전정신경으로 Received Oct 29, 2009 Accepted Nov 18, 2009 Corresponding Author: Jae-Ho Ban, MD, PhD Department of Otorhinolaryngology-Head and Neck Surgery, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, 108 Pyung-dong, Jongro-gu, Seoul , Korea Tel: Fax: Copyrightc 2009 by The Korean Balance Society. All rights reserved. 구심성전정신경의해부구심성전정신경의해부및생리는비교적잘알려져있다. 포유류에서보이는전정신경섬유의직경은대략 10~1 µm 사이에분포하고, 중간굵기의섬유가가장많다. 고양이에서는약 12,000, 원숭이에서는약 18,000, 사람에서는약 20,000여개의구심성신경섬유가존재한다. 1-3 이들은세개의반고리관에는비슷한비율로분포하며, 난형낭에구형낭보다다소많이분포한다. 말초전정의감각세포에분포하는구심성전정신경말단의유형은형태에따라술잔형 (calyx unit), 단추형 (bouton unit), 복합형 (dimorphic) 단위의세가지로분류된다 (Figure 1). Horseradish peroxidase를 intracellular injection하여개개의뉴론과신경섬유를 labelling한연구에서, 굵은신경섬유 (2.81±0.58 µm) 는팽대부릉과 macula의중심부에분포하며, 얇은신경섬유 (1.40±0.37 µm) 는보다더주변부에분포하는경향을보였다. 또한굵은신경섬유는 calyceal 신경말단을가지고 1~5개의 type I 유모세모에분포하며, 얇은신경섬유는 bouton 신경말단으로여러개의 type II 유모세포에분포하였다. 중간굵기의신경섬유 (2.26±0.57 µm) 들은팽대부릉전반에걸쳐고르게분포하였으며복합형신경말단 (dimorphic) 을가지고있었다 (Figure 2). 각신경말단의비율은술잔형 10%, 단추형 20%, 복합형이 70% 정도되었다. 4 상반고리관과측반고리관, 난형난반과구형낭전상부에분 117

2 Res Vestibul Sci Vol. 8, No. 2, Dec a c b d Figure 1. Different types of primary afferent nerve. (a) simple calyx and (b) complex calyxunit, (c) dimorphic unit, and (d) bouton unit. Bar, 10 µm. Vestibular nerve of chinchilla (From Fernandez C et al. J Neurophysiol 1988). Figure 2. Distribution of primary afferent fibers of different diameters (including myelin) within the cristae of humans, monkeys, and chinchillas. The smallest fibers (<2.5 µm) are more numerous at the periphery while the largest fibers (>4.5 µm) are concentrated at the center of the cristae. Intermediate size fibers tend to be equally distributed throughout the cristae. 포된상전정신경 (superior vestibular nerve) 은구형낭과후반고리관에분포한하전정신경과전정신경절에서만나하나의전정신경을이루며뇌간으로주행하여뇌간내에서는상행분지와하행분지로나뉘어주행한다. 구심성전정신경의전기생리구심성전정신경의가장큰특징은평균 50~100 spike/sec 의자발전위를가지고있다는것이다. 이는머리가움직이지않은상태에서도유모세포- 신경접합부로일정량의신경전달물질이지속적으로유리되는것으로생각된다. 전정신경의활동성은머리의회전각속도에따른팽대부릉정의편위정도에비례한다. 전정신경은흥분성자극에의해서는 300~400 spike/sec까지발화할수있지만억제성자극에의해서는 0 spike/sec까지만억제되므로 (inhibitory cutoff), 강한자극에대해서는흥분성반응이억제성반응보다강하다 (Ewald s 2 nd law). 전정구심성신경은극파간간격 (interspike interval) 의분산계수 (coefficient of variation; cv) 에따라규칙적방전섬유 (regular discharging afferents) 와불규칙적방전섬유 (irregular discharging afferents) 로구분된다 (Figure 3). 5 분산계수는극파간격의표준편차를극파간격의평균값으로나누어표시한값으로, 분산계수가작은신경섬유는규칙적으로방전하고, 큰신경섬유는불규칙적으로방전한다는것을의미한다. 그러나전정신경은안정, 억제, 흥분에따라발화율이크게차이가나므로극파간격역시큰차이를보여일정한값을구하기가어렵다. 따라서이러한차이에영향을받지않고발화의규칙성을표시하기위하여 15 ms의극파간격에서평균값으로표준화분산계수 (cv*) 를구하였다. 포유류에서 0.1 이하의 cv* 값을보이면규칙적방전섬유, 0.2 이상이면불규칙적섬유로분류한다 (Figure 4). 5 불규칙적신경섬유는굵은신경섬유에해당하며주로팽대부릉과평형반의중심부에분포하고 type I유모세포와접합한다. 이들은전도속도가빠르고직류전기자극에민감하게반응하며지속적가속도에적응한다. 규칙적신경섬유 118

3 반재호. 전정구심성및원심성신경의전기생리학적반응 A B T, Threshold Figure 3. Stochastic afterhypopolarization model. (A) regular discharging afferents (B) irregular discharging afferents. Figure 5. Origin and course of vestibular efferent pathway, traced with horseradish peroxydase. MVN, medial vestibular nuclei; LVN, lateral vestibular nuclei; V, descending trigeminal root; VI, abducens nucleus; ASO, accessory superior olivary nucleus; DCN, dorsal cochlear nucleus. Figure 4. Afferent response properties according to the coefficient of variation in semicircular canals. 2-Hz, 20- deg/s sinusoidal rotations. 는얇은신경섬유로주로팽대부릉의주변부에분포하며 type I 또는 I, II형유모세포에복합적으로접합한다. 전도속도가느리며회전및직류전기자극에민감도가낮고진자양회전에서주파수에따라일정한이득을보이고고주파수로갈수록위상이변위되어 (phase lead) 예측가능한반응을보인다. 전정신경자발전위발생빈도의규칙성은활동전위발생부위가과분극된후회복되는과정 (afterhyperpolarization) 에의하여결정된다. 6 즉, 활동전위발생후구심성신경섬유세포막의칼륨전도성이점차저하되고막전위가다시역치에도달하면다시발화가일어나는데, 이때신경전달물질의비연속적, 랜덤분비에의하여발생되는흥분성연접 후전위 (excitatory post-synaptic potential, EPSP) 가이러한막전위의회복과겹쳐서일어난다. 규칙적방전섬유는칼륨전도성의저하가느리며일정하게일어나재분극이일정하게발생하며, 전경전달물질의비연속적랜덤분비가상대적으로작아재분극의간격에적은영향을미치며결과적으로일정한시간간격의발화가일어난다. 반면, 불규칙적방전섬유는칼륨전도성이초기에는높다가점차저하되어자발적으로재분극이일어날수있는막전위에도달하지못하고, 이때전경전달물질의비연속적, 랜덤분비에의한 EPSP 에의하여재분극이발생한다. 따라서활동전위의발생은이러한비연속, 랜덤의성향에의하여결정되므로불규칙한시간간격의발화가일어난다. 또한, 불규칙적신경섬유는팽대부릉및평형반의중심부에위치하는데, 팽대부릉의중심부는횡경막모양을하고있고말초부위보다 cupula가얇으므로자극에대하여큰변형이일어난다. 이러한이유로위상성이고높은이득을가지게된다. 반대로, 규칙적신경섬유는주변부에위치하기때문에낮은이득을가진다. 이러한신경말단의위치도규칙성의차이에영향을줄것으로생각된다. 7 전정구심성신경섬유는신경말단접합부의형태에따라서도자발전위발생의규칙성이달라진다. 술잔형단위는중앙부에분포하고불규칙적자발전위를보이고, 단추형단위는주변부에분포하며규칙적자발전위를보인다. 복합형단위는전체적으로고르게분포하나분포부위에따라불규칙과규칙적자발전위모두를발생시킨다. 전정구심성신경섬유는회전자극에대한반응에따라, 119

Res Vestibul Sci Vol. 8, No. 2, Dec. 2009 원심성전정신경의전기생리적반응 Figure 6. Synaptic innervations of afferent and efferent type I and type II vestibular hair cell.

4 Res Vestibul Sci Vol. 8, No. 2, Dec 원심성전정신경의전기생리적반응 Figure 6. Synaptic innervations of afferent and efferent type I and type II vestibular hair cell. C calyx ending; VB, vestibular efferent nerve; SB, synaptic bar. 낮은이득의불규칙적방전섬유 (low gain, irregular afferents; calyceal type), 높은이득의불규칙적방전섬유 (high gain, irregular afferents; dimorphic type), 낮은이득의규칙적방전섬유 (low gain, regular afferents; bouton type) 로구분된다. 일반적으로, 회전각가속도에대한구심성신경의민감도는규칙성정도와역비례하고, 팽대부릉중심에위치한신경은보다더위상적 (phasic) 이며, 이득이높고, 비선형적반응을보이는특징이있다. 8 원심성전정신경의해부 고양이와원숭이를대상으로한연구에서말초전정원심성섬유는약 300개의신경원에서기시되며, 이들 neuron들은양측외측전정신경핵의전방내측과내측전정신경핵의하부, 외향신경핵의외측에존재하는것으로알려졌다 (Figure 5). 9 여기에서기시된전정원심성섬유는전정신경에서상올리브복합체에서기시하는와우원심성신경섬유와함께주행하다가구형낭신경절에서분리된다. 전정원심성신경섬유는전정신경의각분지를따라다섯개의말초전정기관에분포한다. 유모세포와의접합부에서수많은소포를포함하고있는단추형신경말단을형성하며, 한개의원심성신경섬유는여러개의단추형말단을형성하여직접유모세포와연접하거나구심성신경섬유의말단에연접한다 (Figure 6). 따라서신경섬유의수는구심성에비해 1/3 정도로매우적으나신경세포와의접합은구심성신경만큼풍부할수있다. 전정계에서원심성전정신경의역할은알려진바가거의없다고할수있다. 내이의원심성신경에대한연구는와우신경에서먼저이루어졌다. 청각이나진동수용체에대한연구에서, 원심성섬유의주된역할은구심성신경활동을억제하는작용을한다. 어류, 고양이, 개구리등많은종류의동물실험에서와우원심성신경섬유를전기자극했을때반대측와우신경의구심성활동이억제되는현상을보고하였다 그러나거북이나개구리의전정기관에서는구심성활동이증가와감소의두가지반응을보였다고보고하였고, 15,16 toadfish에서는구심성활동의증가가주된반응이었다는보고도있다. 17 한편원숭이와고양이등의포유류에서는전정원심성신경의주된역할이흥분성이라는것이증명되었다. 18,19 하등척추동물에서전정원심성신경원은양측의말초전정수용기로부터자극을받고, yaw축에서양쪽모두의회전자극에의해흥분된다. 20,21 이러한반응을 type III 반응이라고명하게되었다. 이것은 type I 반응이양쪽의회전에각각반대의반응을보이는것과는대조적이다. 원심성반응은어류나개구리에서는동측의뇌간에만원심성신경원이존재하는반면, 포유류에서는외간의양측에서모두원심성신경원이발견된다는중추원심성경로의차이로다르게나타날수있다고생각된다. 신경반응은구심성섬유의방전규칙성 (discharge regularity) 에따라다르게나타난다. 불규칙적구심성섬유는크게반응할수있어서자발전위 (background discharge) 를 100 spike/s까지증가시킨다. 이러한자발전위의증가는 10~100 ms의시간상수를갖는 fast excitation과동역학적으로수초로측정되는 slow excitation으로구성된다. 규칙적구심성섬유에서는원심성신경자극에대한반응이작고 (<10 spikes/s), slow excitation이주반응이다. 또한이러한반응은마취상태보다 decerebration 상태와같이마취되지않은상태에서더크게나타나는것을확인할수있었다. 22 현재까지의연구결과로 slow response는 tonic activity에영향을주는이론에합당하고, fast response는빠른머리움직임시에발생하는 phasic response를조절하는데기여한다고할수있다. Afferent neurons이높은 rate를유지하며지속적인형태로방전하는경우가없다는점을기초로유추해보면, large efferent mediated fast response는원심성신경원의 high-frequency bursts에의존한다고추정할수있으며, 120

5 반재호. 전정구심성및원심성신경의전기생리학적반응 slow response는원심성신경계에의하여구심성반응의자발전위를변경할수있게하는기전을제공하는것으로생각할수있다. 23 REFERENCES 1. Gacek RR. The course and central termination of first order neurons supplying vestibular endorgans in the cat. Acta Otolaryngol Suppl 1969;254: Rasmussen AT. Studies of the eighth cranial nerve of man. Laryngoscope. 1940;50: Gacek RR, Rasmussen GL. Fiber analysis of the statoacoustic nerve of guinea pig, cat, and monkey. Anat Rec 1961;139: Baloh RW, Honrubia V. The peripheral vestibular system. Clinical neurophysiology of the vestibular system, 2nd ed. Philadelphia: FA Davis Company, Baird RA, Desmadryl G, Fernandez C, Goldberg JM. The vestibular nerve of the chinchilla. II. Relation between afferent response properties and peripheral innervation patterns in the semicircular canals. J Neurophysiol 1988;60: Smith CE, Goldberg JM. A stochastic afterhyperpolarization model of repetitive activity in vestibular afferents. Biol Cybern 1986;54: Goldberg JM. Afferent diversity and the organization of central vestibular pathways. Exp Brain Res 2000;130: Goldberg JM, Fernandez C. Responses of peripheral vestibular neurons to angular and linear accelerations in the squirrel monkey. Acta Otolaryngol 1975;80: Gacek RR, Lyon M. The localization of vestibular efferent neurons in the kitten with horseradish peroxidase. Acta Otolaryngol 1974;77: Wiederhold ML, Kiang NY. Effects of electric stimulation of the crossed olivocochlear bundle on single auditorynerve fibers in the cat. J Acoust Soc Am 1970;48: Flock A, Russell IJ. The post-synaptic action of efferent fibres in the lateral line organ of the burbot Lota lota. J Physiol 1973;235: Furukawa T. Effects of efferent stimulation on the saccule of goldfish. J Physiol 1981;315: Ashmore JF, Russell IJ. Effects of efferent nerve stimulation on hair cells of the frog sacculus. J Physiol. 1982; 329: Art JJ, Fettiplace R, Fuchs PA. Synaptic hyperpolarization and inhibition of turtle cochlear hair cells. J Physiol 1984; 356: Rossi ML, Prigioni I, Valli P, Casella C. Activation of the efferent system in the isolated frog labyrinth: effects on the afferent EPSPs and spike discharge recorded from single fibres of the posterior nerve. Brain Res 1980;185: Brichta AM, Goldberg JM. Responses to efferent activation and excitatory response-intensity relations of turtle posterior-crista afferents. J Neurophysiol 2000;83: Boyle R, Carey JP, Highstein SM. Morphological correlates of response dynamics and efferent stimulation in horizontal semicircular canal afferents of the toadfish, Opsanus tau. J Neurophysiol 1991;66: Goldberg JM, Fernandez C. Efferent vestibular system in the squirrel monkey: anatomical location and influence on afferent activity. J Neurophysiol 1980;43: McCue MP, Guinan JJ Jr. Influence of efferent stimulation on acoustically responsive vestibular afferents in the cat. J Neurosci 1994;14: Blanks RH, Precht W. Functional characterization of primary vestibular afferents in the frog. Exp Brain Res 1976; 25: Hartmann R, Klinke R. Efferent activity in the goldfish vestibular nerve and its influence on afferent activity. Pflugers Arch 1980;388: Plotnik M, Marlinski V, Goldberg JM. Reflections of efferent activity in rotational responses of chinchilla vestibular afferents. J Neurophysiol 2002;88: Marlinski V, Plotnik M, Goldberg JM. Efferent actions in the chinchilla vestibular labyrinth. J Assoc Res Otolaryngol 2004;5:

대한안신경의학회지 : 제 5 권제 1 호 Clin Neuroophthalmol 5(1):15-19, June 2015 ISSN: REVIEW 전정안반사 최정윤 고려대학교안산병원신경과 Vestibulo-ocular Reflex Jeong-Yoon Cho

대한안신경의학회지 : 제 5 권제 1 호 Clin Neuroophthalmol 5(1):15-19, June 2015 ISSN: REVIEW 전정안반사 최정윤 고려대학교안산병원신경과 Vestibulo-ocular Reflex Jeong-Yoon Cho 대한안신경의학회지 : 제 5 권제 1 호 ISSN: 2234-0971 REVIEW 전정안반사 최정윤 고려대학교안산병원신경과 Vestibulo-ocular Reflex Jeong-Yoon Choi, MD Department of Neurology, Korea University Ansan Hospital, Ansan, Korea In this review, anatomical