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. 2001 Aug 31;3(1):89–106. doi: 10.1007/s101620010091

Conductive Hearing Loss Results in Changes in Cytochrome Oxidase Activity in Gerbil Central Auditory System

Debara L Tucci 1,✉, Nell B Cant 2, Dianne Durham 3
PMCID: PMC3202368  PMID: 12083727

Abstract

Conductive hearing loss (CHL) restricts auditory input to an intact peripheral auditory system. Effects of deprivation on the central auditory system (CAS) have been debated, although a number of studies support the hypothesis that CHL can cause modification of CAS structure and function. The present study was designed to test the hypothesis that unilateral CHL results in a decrease in cytochrome oxidase (CO) activity in CAS nuclei that receive major afferent input from the affected ear. Gerbils at postnatal day 12 (P21) or 6–8 weeks underwent left unilateral CHL (malleus removal), cochlear ablation, or a sham surgical procedure. After a survival time of 48 hours or 3 weeks, animals were sacrificed and tissue was processed for cytochrome oxidase histochemistry. Optical density (OD) measurements were made from individual neurons in the anteroventral cochlear nucleus (AVCN) and from medial and lateral dendritic fields in the medial superior olivary nucleus (MSO), the lateral superior olivary nucleus, and the inferior colliculus. The width of the CO-stained neuropil in MSO was also measured as an estimate of dendritic length. OD measures were corrected to neutral areas of the brain. Cochlear ablation caused significant decreases in CO activity in left lower brainstem nuclei, particularly in adult animals. Following CHL, a significant decrease in CO activity was observed in the ipsilateral AVCN and a significant increase was observed in the contralateral AVCN. Cochlear ablation resulted in decreased width of MSO neuropil containing dendrites that receive primary input from the ablated ear. CHL resulted in a significant increase in the width of MSO neuropil on both sides of the brain in the P21 animals that survived 3 weeks but not in P21 animals that survived only 48 hours or in the adult animals. Unilateral CHL is associated with changes in CO activity in the AVCN and may affect MSO dendritic length in younger animals.

Keywords: deprivation, plasticity, brain metabolism

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Acknowledgements

The authors wish to thank Dr. Deb Park for valuable technical assistance and assistance with statistical analysis, and Sandy Parsons for expert technical assistance. We gratefully acknowledge the helpful comments of two anonymous reviewers. Supported by NIH grants K08DC00125 (DLT), DC01589 (DD), and DC00135 (NBC).

References

  • 1.Blatchley BJ, Williams JE, Coleman JR. Age-dependent effect of acoustic deprivation on spherical cells of the rat anteroventral cochlear nucleus. Exp. Neurol. 1983;80:81–93. doi: 10.1016/0014-4886(83)90008-0. [DOI] [PubMed] [Google Scholar]
  • 2.Born DE, Durham D, Rubel EW. Afferent influences on brainstem auditory nuclei in the chick: Nucleus magnocellularis neuronal activity following cochlea removal. Brain Res. 1991;557:37–47. doi: 10.1016/0006-8993(91)90113-A. [DOI] [PubMed] [Google Scholar]
  • 3.Born DE, Rubel EW. Afferent influences on brain stem auditory nuclei of the chicken: Neuron number and size following cochlea removal. J. Comp. Neurol. 1985;231:435–445. doi: 10.1002/cne.902310403. [DOI] [PubMed] [Google Scholar]
  • 4.Born DE, Rubel EW. Afferent influences on brain stem auditory nuclei of the chicken: presynaptic action potentials regulate protein synthesis in nucleus magnocellularis neurons. J. Neurosci. 1988;8:901–919. doi: 10.1523/JNEUROSCI.08-03-00901.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Brugge JF, Orman SS, Coleman JR, Chan JCK, Phillips DP. Binaural interactions in cortical area AI of cats reared with unilateral atresia of the external ear canal. Hear. Res. 1985;20:275–287. doi: 10.1016/0378-5955(85)90032-2. [DOI] [PubMed] [Google Scholar]
  • 6.Clopton BM, Silverman MS. Plasticity of binaural interaction. II. Critical period and changes in midline response. J. Neurophysiol. 1977;40:1275–1280. doi: 10.1152/jn.1977.40.6.1275. [DOI] [PubMed] [Google Scholar]
  • 7.Clopton BM, Silverman MS. Changes in latency and duration of neural responding following developmental auditory deprivation. Exp. Brain Res. 1978;32:39–47. doi: 10.1007/BF00237388. [DOI] [PubMed] [Google Scholar]
  • 8.Coleman JR, Blatchley BJ, Williams JE. Development of the dorsal and ventral cochlear nuclei in rat and effects of acoustic deprivation. Dev. Brain Res. 1982;4:119–123. doi: 10.1016/0165-3806(82)90104-3. [DOI] [PubMed] [Google Scholar]
  • 9.Coleman JR, O'Connor P. Effects of monaural and binaural sound deprivation on cell development in the anteroventral cochlear nucleus of rats. Exp. Neurol. 1979;64:553–566. doi: 10.1016/0014-4886(79)90231-0. [DOI] [PubMed] [Google Scholar]
  • 10.Conlee JW, Parks TN. Age- and position-dependent effects of monaural acoustic deprivation in nucleus magnocellularis of the chicken. J. Comp. Neurol. 1981;202:373–384. doi: 10.1002/cne.902020307. [DOI] [PubMed] [Google Scholar]
  • 11.Conlee JW, Parks TN. Late appearance and deprivation-sensitive growth of permanent dendrites in the avian cochlear nucleus, n. magnocellularis. J. Comp. Neurol. 1983;217:216–226. doi: 10.1002/cne.902170208. [DOI] [PubMed] [Google Scholar]
  • 12.Darriet D, Der T, Collins RC. Distribution of cytochrome oxidase in rat brain: studies with diaminobenzidine histochemistry in vitro and [14C]cyanide tissue labeling in vivo. J. Cereb. Blood Flow Metab. 1986;6:8–14. doi: 10.1038/jcbfm.1986.2. [DOI] [PubMed] [Google Scholar]
  • 13.Deitch JS, Rubel EW. Afferent influences on brain stem auditory nuclei of the chicken: Time course and specificity of dendritic atrophy following deafferentation. J. Comp. Neurol. 1984;229:66–79. doi: 10.1002/cne.902290106. [DOI] [PubMed] [Google Scholar]
  • 14.Doyle WJ, Webster DB. Neonatal conductive hearing loss does not compromise brainstem auditory function and structure in rhesus monkeys. Hear. Res. 1991;54:145–151. doi: 10.1016/0378-5955(91)90144-X. [DOI] [PubMed] [Google Scholar]
  • 15.Durham D, Matschinsky FMM, Rubel EW. Altered malate dehydrogenase activity in n. magnocellularis of the chicken following cochlea removal. Hear. Res. 1993;70:151–159. doi: 10.1016/0378-5955(93)90153-R. [DOI] [PubMed] [Google Scholar]
  • 16.Durham D, Rubel EW. Afferent influences on brain stem auditory nuclei of the chicken: Changes in succinate dehydrogenase activity following cochlea removal. J. Comp. Neurol. 1985;231:446–456. doi: 10.1002/cne.902310404. [DOI] [PubMed] [Google Scholar]
  • 17.Feng AS, Rogowski BA. Effects of monaural and binaural occlusion on the morphology of neurons in the medial superior olivary nucleus of the rat. Brain Res. 1980;189:530–534. doi: 10.1016/0006-8993(80)90112-2. [DOI] [PubMed] [Google Scholar]
  • 18.Friedlander MJ, Martin KAC, Wassenhove–McCarthy D. Effects of monocular visual deprivation on geniculocortical innervation of area 18 in cat. J. Neurosci. 1991;11:3268–3288. doi: 10.1523/JNEUROSCI.11-10-03268.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Gray L, Smith Z, Rubel EW. Developmental and experimental changes in dendritic symmetry in n. laminaris of the chick. Brain Res. 1982;244:360–364. doi: 10.1016/0006-8993(82)90098-1. [DOI] [PubMed] [Google Scholar]
  • 20.Hall JW, Derlacki EL. Binaural hearing after middle ear surgery: masking-level differences for interaural time and amplitude cues. Audiology. 1988;27:89–98. doi: 10.3109/00206098809081579. [DOI] [PubMed] [Google Scholar]
  • 21.Hall JW, Grose JH, Pillsbury HC. Long-term effects of chronic otitis media on binaural hearing in children. Arch. Otolaryngol. Head Neck Surg. 1995;121:847–852. doi: 10.1001/archotol.1995.01890080017003. [DOI] [PubMed] [Google Scholar]
  • 22.Hashisaki GT, Rubel EW. Effects of unilateral cochlea removal on anteroventral cochlear nucleus neurons in developing gerbils. J. Comp. Neurol. 1989;283:465–473. doi: 10.1002/cne.902830402. [DOI] [PubMed] [Google Scholar]
  • 23.Hyde GE, Durham D. Cytochrome oxidase response to cochlea removal in chicken auditory brainstem neurons. J. Comp. Neurol. 1990;297:329–339. doi: 10.1002/cne.902970302. [DOI] [PubMed] [Google Scholar]
  • 24.Hyde GE, Durham D. Rapid increases in mitochondrial volume in nucleus magnocellularis neurons following cochlea removal. J. Comp. Neurol. 1994a;339:27–48. doi: 10.1002/cne.903390105. [DOI] [PubMed] [Google Scholar]
  • 25.Hyde GE, Durham D. Increased deafferentation-induced cell death in chick brainstem auditory neurons following blockade of mitochondrial protein synthesis with chloramphenicol. J. Neurosci. 1994b;14:291–300. doi: 10.1523/JNEUROSCI.14-01-00291.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Hyson RL, Rubel EW. Transneuronal regulation of protein synthesis in the brain-stem auditory system of the chick requires synaptic activation. J. Neurosci. 1989;9:2835–2845. doi: 10.1523/JNEUROSCI.09-08-02835.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Keilmann A, Herdegen T. The c-Fos transcription factor in the auditory pathway of the juvenile rat: effects of acoustic deprivation and repetitive stimulation. Brain Res. 1997;753:291–298. doi: 10.1016/S0006-8993(97)00034-6. [DOI] [PubMed] [Google Scholar]
  • 28.Knudsen EI. Mechanisms of experienced-dependent plasticity in the auditory localization pathway of the barn owl. J. Comp. Physiol. 1999;185:305–321. doi: 10.1007/s003590050391. [DOI] [PubMed] [Google Scholar]
  • 29.Koerber KC, Pfeiffer RR, Warr WB, Kiang YS. Spontaneous spike discharges from single units in the cochlear nucleus after destruction of the cochlea. Exp. Neurol. 1966;16:119–130. doi: 10.1016/0014-4886(66)90091-4. [DOI] [PubMed] [Google Scholar]
  • 30.Lowry OH. Energy metabolism in brain and its control. In: Ingvar DH, Lassen NA, editors. Brain Work. The Coupling of Function, Metabolism and Blood Flow in the Brain. New York: Academic Press; 1975. pp. 48–63. [Google Scholar]
  • 31.Mawe GM, Gershon MD. Functional heterogeneity in the myenteric plexus: Demonstration using cytochrome oxidase as a verified cytochemical probe of the activity of individual enteric neurons. J. Comp. Neurol. 1986;249:381–391. doi: 10.1002/cne.902490305. [DOI] [PubMed] [Google Scholar]
  • 32.Moore DR. Auditory brainstem of the ferret: Bilateral cochlear lesions in infancy do not affect the number of neurons projecting from the cochlear nucleus to the inferior colliculus. Exp. Brain Res. 1990;54:125–130. doi: 10.1016/0165-3806(90)90072-7. [DOI] [PubMed] [Google Scholar]
  • 33.Moore DR. Development and plasticity of the ferret auditory system. In: Altschuler RA, Bobbin RP, Clopton BM, Hoffman DW, editors. Neurobiology of Hearing: The Central Auditory System. New York: Raven Press; 1991. pp. 461–475. [Google Scholar]
  • 34.Moore DR, Hutchings ME, King AJ, Kowalchuk NE. Auditory brainstem of the ferret: Some effects of rearing with a unilateral ear plug on the cochlea, cochlear nucleus, and projections to the inferior colliculus. J. Neurosci. 1989;9:1213–1222. doi: 10.1523/JNEUROSCI.09-04-01213.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Moore DR, Irvine DRF. Plasticity of binaural interaction in the cat inferior colliculus. Brain Res. 1981;208:198–202. doi: 10.1016/0006-8993(81)90632-6. [DOI] [PubMed] [Google Scholar]
  • 36.Moore DR, Kitzes LM. Projections from the cochlear nucleus to the inferior colliculus in normal and neonatally cochlea-ablated gerbils. J. Comp. Neurol. 1985;240:180–195. doi: 10.1002/cne.902400208. [DOI] [PubMed] [Google Scholar]
  • 37.Nordeen KW, Killackey HP, Kitzes LM. Ascending auditory projections to the inferior colliculus in the adult gerbil, Meriones unguiculatus. J. Comp. Neurol. 1983a;214:131–143. doi: 10.1002/cne.902140203. [DOI] [PubMed] [Google Scholar]
  • 38.Nordeen KW, Killackey HP, Kitzes LM. Ascending projections to the inferior colliculus following unilateral cochlear ablation in the neonatal gerbil, Meriones unguiculatus. J. Comp. Neurol. 1983b;214:144–153. doi: 10.1002/cne.902140204. [DOI] [PubMed] [Google Scholar]
  • 39.Pasic TR, Rubel EW. Rapid changes in cochlear nucleus cell size following blockade of auditory nerve electrical activity in gerbils. J. Comp. Neurol. 1989;283:474–480. doi: 10.1002/cne.902830403. [DOI] [PubMed] [Google Scholar]
  • 40.Pillsbury HC, Grose JH, Hall JW. Otitis media with effusion in children: binaural hearing before and after corrective surgery. Arch. Otolaryngol. Head Neck Surg. 1991;117:718–723. doi: 10.1001/archotol.1991.01870190030008. [DOI] [PubMed] [Google Scholar]
  • 41.Powell TPS, Erulkar SD. Transneuronal cell degeneration in the auditory relay nuclei of the cat. J. Anat. 1962;96:249–268. [PMC free article] [PubMed] [Google Scholar]
  • 42.Rubel EW, Hyson RL, Durham D. Afferent regulation of neurons in the brain stem auditory system. J. Neurobiol. 1990;21:169–196. doi: 10.1002/neu.480210112. [DOI] [PubMed] [Google Scholar]
  • 43.Rubel EW, Smith ZDJ, Steward O. Sprouting in the avian brainstem auditory pathway: Dependence on dendritic integrity. J. Comp. Neurol. 1981;202:397–414. doi: 10.1002/cne.902020309. [DOI] [PubMed] [Google Scholar]
  • 44.Ryan AF. Hearing sensitivity of the mongolian gerbil, Meriones unguiculatus. J. Acoust. Soc. Am. 1976;59:1222–1226. doi: 10.1121/1.380961. [DOI] [PubMed] [Google Scholar]
  • 45.Ryugo DK, Rosenbaum BT, Kim PJ, Niparko JP, Saada AA. Single unit recordings in the auditory nerve of congenitally deaf white cats: morphological correlates in the cochlea and cochlear nucleus. J. Comp. Neurol. 1998;397:532–548. doi: 10.1002/(SICI)1096-9861(19980810)397:4<532::AID-CNE6>3.0.CO;2-2. [DOI] [PubMed] [Google Scholar]
  • 46.Sanes DH, Constantine–Paton M. The sharpening of frequency tuning curves requires patterned activity during development in the mouse, Mus musculus. J. Neurosci. 1985a;5:1152–1166. doi: 10.1523/JNEUROSCI.05-05-01152.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Sanes DH, Constantine–Paton M. The development of stimulus following in the cochlear nerve and inferior colliculus of the mouse. Dev. Brain Res. 1985b;22:255–267. doi: 10.1016/0165-3806(85)90177-4. [DOI] [PubMed] [Google Scholar]
  • 48.Sanes DH, Siverls V. Development and specificity of inhibitory terminal arborization in the central nervous system. J. Neurobiol. 1991;22:837–854. doi: 10.1002/neu.480220805. [DOI] [PubMed] [Google Scholar]
  • 49.Sherman SM, Spear PD. Organization of visual pathways in normal and visually deprived cats. Physiol. Rev. 1982;62:738–855. doi: 10.1152/physrev.1982.62.2.738. [DOI] [PubMed] [Google Scholar]
  • 50.Shore SE, Vass Z, Wys N, Altschuler RA. The trigeminal ganglion innervates the auditory brainstem. J. Comp. Neurol. 2000;419:271–285. doi: 10.1002/(sici)1096-9861(20000410)419:3<271::aid-cne1>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  • 51.Sie KCY, Rubel EW. Rapid changes in protein synthesis and cell size in the cochlear nucleus following eighth nerve activity blockade or cochlea ablation. J. Comp. Neurol. 1992;320:501–508. doi: 10.1002/cne.903200407. [DOI] [PubMed] [Google Scholar]
  • 52.Silverman MS, Clopton BM. Plasticity of binaural interaction. I. Effect of early auditory deprivation. J. Neurophysiol. 1977;40:1266–1274. doi: 10.1152/jn.1977.40.6.1266. [DOI] [PubMed] [Google Scholar]
  • 53.Smith ZDJ, Gray L, Rubel EW. Afferent influences on brainstem auditory nuclei of the chicken: N. laminaris dendritic length following monaural conductive hearing loss. J. Comp. Neurol. 1983;220:199–205. doi: 10.1002/cne.902200207. [DOI] [PubMed] [Google Scholar]
  • 54.Tierney TS, Russell FA, Moore DR. Susceptibility of developing cochlear nucleus neurons to deafferentation-induced death abruptly ends just before the onset of hearing. J. Comp. Neurol. 1997;378:295–306. doi: 10.1002/(SICI)1096-9861(19970210)378:2&#x0003c;295::AID-CNE11&#x0003e;3.0.CO;2-R. [DOI] [PubMed] [Google Scholar]
  • 55.Trune DR. Influence of neonatal cochlear removal on the development of mouse cochlear nucleus: I. Number, size, and density of its neurons. J. Comp. Neurol. 1982a;209:409–424. doi: 10.1002/cne.902090410. [DOI] [PubMed] [Google Scholar]
  • 56.Trune DR. Influence of neonatal cochlear removal on the development of mouse cochlear nucleus: II. Dendritic morphometry of its neurons. J. Comp. Neurol. 1982b;209:425–434. doi: 10.1002/cne.902090411. [DOI] [PubMed] [Google Scholar]
  • 57.Trune DR, Kiessling AA. Decreased protein synthesis in cochlear nucleus following developmental auditory deprivation. Hear. Res. 1988;35:259–264. doi: 10.1016/0378-5955(88)90122-0. [DOI] [PubMed] [Google Scholar]
  • 58.Trune DR, Morgan CR. Stimulation-dependent development of neuronal cytoplasm in mouse cochlear nucleus. Hear. Res. 1988a;33:141–150. doi: 10.1016/0378-5955(88)90027-5. [DOI] [PubMed] [Google Scholar]
  • 59.Trune DR, Morgan CR. Influences of developmental auditory deprivation on neuronal ultrastructure in the mouse anteroventral cochlear nucleus. Dev. Brain Res. 1988b;42:304–308. doi: 10.1016/0165-3806(88)90249-0. [DOI] [PubMed] [Google Scholar]
  • 60.Tucci DL, Born DE, Rubel EW. Changes in spontaneous activity and CNS morphology associated with conductive and sensorineural hearing loss in chickens. Ann. Otol. Rhinol. Laryngol. 1987;96:343–350. doi: 10.1177/000348948709600321. [DOI] [PubMed] [Google Scholar]
  • 61.Tucci DL, Cant NB, Durham D. Conductive hearing loss results in a decrease in central auditory system activity in the young gerbil. Laryngoscope. 1999;109:1359–1371. doi: 10.1097/00005537-199909000-00001. [DOI] [PubMed] [Google Scholar]
  • 62.Tucci DL, Rubel EW. Afferent influences on brain stem auditory nuclei of the chicken: Effects of conductive and sensorineural hearing loss on n. magnocellularis. J. Comp. Neurol. 1985;238:371–381. doi: 10.1002/cne.902380402. [DOI] [PubMed] [Google Scholar]
  • 63.Webster DB. Auditory neuronal sizes after a unilateral conductive hearing loss. Exp. Neurol. 1983a;79:130–140. doi: 10.1016/0014-4886(83)90384-9. [DOI] [PubMed] [Google Scholar]
  • 64.Webster DB. A critical period during postnatal auditory development of mice. Int. J. Pediatr. Otorhinolaryngol. 1983b;6:107–118. doi: 10.1016/s0165-5876(83)80111-6. [DOI] [PubMed] [Google Scholar]
  • 65.Webster DB. Late onset of auditory deprivation does not affect brainstem auditory neuron soma size. Hear. Res. 1983c;12:145–147. doi: 10.1016/0378-5955(83)90123-5. [DOI] [PubMed] [Google Scholar]
  • 66.Webster DB. Conductive hearing loss affects the growth of cochlear nuclei over an extended period of time. Hear. Res. 1988;32:185–192. doi: 10.1016/0378-5955(88)90090-1. [DOI] [PubMed] [Google Scholar]
  • 67.Webster DB, Webster M. Neonatal sound deprivation affects brain stem auditory nuclei. Arch. Otolaryngol. Head Neck Surg. 1977;103:392–396. doi: 10.1001/archotol.1977.00780240050006. [DOI] [PubMed] [Google Scholar]
  • 68.Webster DB, Webster M. Effects of neonatal conductive hearing loss on brain stem auditory nuclei. Ann. Otol. 1979;88:684–688. doi: 10.1177/000348947908800515. [DOI] [PubMed] [Google Scholar]
  • 69.Wilmington D, Gray L, Jahrsdoerfer R. Binaural processing after corrected congenital unilateral conductive hearing loss. Hear. Res. 1994;74:99–114. doi: 10.1016/0378-5955(94)90179-1. [DOI] [PubMed] [Google Scholar]
  • 70.Wong–Riley MTT. Cytochrome axidase: An endogenous metabolic marker for neuronal activity. Trends Neurosci. 1989;12:94–101. doi: 10.1016/0166-2236(89)90165-3. [DOI] [PubMed] [Google Scholar]
  • 71.Wong–Riley MTT, Merzenich MM, Leake PA. Changes in endogenous enzymatic reactivity of DAB induced by neuronal inactivity. Brain Res. 1978;141:185–192. doi: 10.1016/0006-8993(78)90629-7. [DOI] [PubMed] [Google Scholar]
  • 72.Wong–Riley MTT, Walsh SM, Leake–Jones PA, Merzenich MM. Maintenance of neuronal activity by electrical stimulation of unilaterally deafened cats demonstrable with cytochrome oxidase technique. Ann. Otol. 1981;90(suppl 82):30–32. doi: 10.1177/00034894810902s211. [DOI] [PubMed] [Google Scholar]
  • 73.Woolf NK, Ryan AF. The development of auditory function in the cochlea of the mongolian gerbil. Hear. Res. 1984;13:277–283. doi: 10.1016/0378-5955(84)90081-9. [DOI] [PubMed] [Google Scholar]
  • 74.Woolf NK, Ryan AF. Ontogeny of neural discharge patterns in the ventral cochlear nucleus of the mongolian gerbil. Brain Res. 1985;17:131–147. doi: 10.1016/0165-3806(85)90138-5. [DOI] [PubMed] [Google Scholar]

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