Elsevier

Neurobiology of Aging

Volume 33, Issue 12, December 2012, Pages 2892-2902
Neurobiology of Aging

Regular article
Efferent synapses return to inner hair cells in the aging cochlea

https://doi.org/10.1016/j.neurobiolaging.2012.02.007Get rights and content

Abstract

Efferent innervation of the cochlea undergoes extensive modification early in development, but it is unclear if efferent synapses are modified by age, hearing loss, or both. Structural alterations in the cochlea affecting information transfer from the auditory periphery to the brain may contribute to age-related hearing deficits. We investigated changes to efferent innervation in the vicinity of inner hair cells (IHCs) in young and old C57BL/6 mice using transmission electron microscopy to reveal increased efferent innervation of IHCs in older animals. Efferent contacts on IHCs contained focal presynaptic accumulations of small vesicles. Synaptic vesicle size and shape were heterogeneous. Postsynaptic cisterns were occasionally observed. Increased IHC efferent innervation was associated with a smaller number of afferent synapses per IHC, increased outer hair cell loss, and elevated auditory brainstem response thresholds. Efferent axons also formed synapses on afferent dendrites but with a reduced prevalence in older animals. Age-related reduction of afferent activity may engage signaling pathways that support the return to an immature state of efferent innervation of the cochlea.

Introduction

It is estimated that 25% of people aged 65–75 years and 70%–80% of people older than age 75 suffer from hearing loss associated with aging (Lin et al., 2011, Sprinzl and Riechelmann, 2010). Cumulative structural alterations in the cochlea affecting information transfer from the auditory periphery to the brain may contribute to age-related hearing deficits. Changes in the proportion of low spontaneous rate auditory nerve fibers observed with age (Schmiedt et al., 1996) may be linked to afferent synapse alterations at the inner hair cell (IHC) including loss of afferent terminals; enlarged synaptic terminals, mitochondria, postsynaptic densities (PSDs), and synaptic bodies; flattened PSDs; increased prevalence of PSDs associated with multiple or missing synaptic bodies; and increased synaptic vesicle density (Stamataki et al., 2006).

Changes in efferent feedback to the cochlea also may occur during age-related hearing deficits. The mammalian olivocochlear efferent system consists of 2 distinct pathways: a medial olivocochlear (MOC) component that projects bilaterally from the superior olivary complex to the outer hair cells (OHCs) and a lateral olivocochlear (LOC) component that projects ipsilaterally from the superior olivary complex to the auditory nerve dendrites contacting IHCs (summarized in Fig. 1; recently reviewed by Brown, 2011). These projection patterns reflect the mature innervation of adult animals. Activation of the MOC component causes hyperpolarization of OHCs by acetylcholine release (Blanchet et al., 1996, Evans, 1996), resulting in modulation of the active mechanical properties of the cochlea (Russell and Murugasu, 1997). The resulting suppression of the cochlear response modulates the auditory nerve's dynamic range (e.g., Dolan and Nuttall, 1988, Galambos, 1956, Kawase and Liberman, 1993, Kawase et al., 1993, Liberman and Brown, 1986, Winslow and Sachs, 1987), enhances the representation of transient signals in noise (Dolan and Nuttall, 1988, Kawase and Liberman, 1993, Winslow and Sachs, 1987), protects the auditory system from acoustic trauma (e.g., Kujawa and Liberman, 1997, Lauer and May, 2011, Maison et al., 2002, Rajan, 2000). Deficient MOC function has been reported in older human listeners and mice (Jacobson et al., 2003; Zettel et al., 2007). The functional role of the LOC system is poorly understood, but it appears to modify afferent activity through various neurotransmitter systems and may protect the ear from acoustic overexposure and/or balance the sensitivity of the 2 ears to sensory stimulation (Darrow et al., 2006, Darrow et al., 2007, Le Prell et al., 2003, Le Prell et al., 2005).

Efferent innervation of the cochlea undergoes extensive modification early in development (Simmons et al., 2011), including the loss of efferent contacts from IHCs near the onset of hearing. It is not known if these changes are permanent, or if they vary with acoustic damage, aging, or both. C57BL/6J mice show age-related loss of MOC terminals contacting OHCs (Fu et al., 2010), but virtually nothing is known about age-related changes to efferent innervation in the IHC area. In the present study, we investigated changes to efferent innervation in the vicinity of IHCs in aged mice.

Section snippets

Subjects

Adult female C57BL/6J (C57) mice were studied at 2–3 months of age (n = 3) and 8–11 months of age (n = 3). The efferent innervation of the 22 kHz region of the cochlea was examined for a total of 10 cells from young animals and 8 cells from old animals using transmission electron microscopy. A total of 3 axosomatic efferent synapses and 348 axodendritic efferent synapses were observed in young animals, and 35 axosomatic efferent synapses and 60 axodendritic synapses were observed in old

Ultrastructure of efferent nerve endings in the IHC area in young and old animals

Axodendritic efferent synapses were common in young animals. While efferent terminals occasionally approached the IHC in young animals, axosomatic synapses were rare. In contrast, both axosomatic and axodendritic efferent synapses were observed in older animals. Fig. 2A shows a section through the basal (synaptic) pole of an IHC of an older animal that is contacted by 4 axosomatic efferent terminals. Sections through the basal pole of IHCs from older animals demonstrated irregular shaped

Discussion

We have shown that efferent innervation of mouse IHCs increases with age-related hearing loss. Transient efferent contacts with IHCs occurring early in development have been known to exist for some time in rodents, but these contacts are lost from the IHC by the time of hearing onset (Katz et al., 2004, Simmons et al., 2011). Here we provide evidence for increased IHC-associated efferents in aging adult animals.

The observed age-related change in efferent innervation of IHCs in hearing-impaired

Disclosure statement

The authors disclose no conflicts of interest.

All procedures were conducted in accordance with protocols approved by the Johns Hopkins University Animal Care and Use Committee.

Acknowledgements

This research was supported by NIH grants DC00143, DC05909, DC005211, DC001508, DC000232, DC000023, DC009353, DC004395, NEI grant EY001765, NHMRC grant 1009482, and grants from the American Hearing Research Foundation, National Organization for Hearing Research, Deafness Research Foundation, and Garnett Passe and Rodney Williams Memorial Foundation. We thank Zayer Minh for data analysis assistance; Sofia Stamataki, Mohamed Lehar, and Ioan Lina for technical assistance; and Heather Graham for

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