Urocortin-Expressing Olivocochlear Neurons Exhibit Tonotopic and Developmental Changes in the Auditory Brainstem and in the Innervation of the Cochlea

Division of Neurobiology, Department of Biology II, Ludwig-Maximilians-Universitaet Muenchen, 82152 Martinsried, Germany.
The Journal of Comparative Neurology (Impact Factor: 3.23). 10/2011; 519(14):2758-78. DOI: 10.1002/cne.22650
Source: PubMed


The mammalian cochlea is under direct control of two groups of cholinergic auditory brainstem neurons, the medial and the lateral olivocochlear neurons. The former modulate the electromechanical amplification in outer hair cells and the latter the transduction of inner hair cells to auditory nerve fibers. The lateral olivocochlear neurons express not only acetylcholine but a variety of co-transmitters including urocortin, which is known to regulate homeostatic responses related to stress; it may also be related to the ontogeny of hearing as well as the generation of hearing disorders. In the present study, we investigated the distribution of urocortin-expressing lateral olivocochlear neurons and their connectivity and distribution of synaptic terminals in the cochlea of juvenile and adult gerbils. In contrast to most other rodents, the gerbil's audiogram covers low frequencies similar to humans, although their communication calls are exclusively in the high-frequency domain. We confirm that in the auditory brainstem urocortin is expressed exclusively in neurons within the lateral superior olive and their synaptic terminals in the cochlea. Moreover, we show that in adult gerbils urocortin expression is restricted to the medial, high-frequency processing, limb of the lateral superior olive and to the mid and basal parts of the cochlea. The same pattern is present in juvenile gerbils shortly before hearing onset (P 9) but transiently disappears after hearing onset, when urocortin is also expressed in low-frequency processing regions. These results suggest a possible role of urocortin in late cochlear development and in the processing of social calls in adult animals.

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    • "The specificity of all primary antibodies used has been previously published and the relevant publications are indicated for the respective antibodies. The primary antibodies used were: chicken anti-Map2 (1∶1000, Neuromics, CH22103 [45], [63]), mouse anti-ATPase (1∶1000, DSHB, a5 [64], [65]), rabbit anti-synapsin (1∶100, SySy, 106 002 [66]), rabbit anti-GLUT3 (1∶100, abcam, ab41525 [62], [67]) and mouse anti-mitochondria (1∶500, abcam, ab3298 [68]). The anti-mitochondria antibody was raised against a non-glycosylated protein component of the mitochondrial membrane obtained from a partially purified mitochondrial preparation. "
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    ABSTRACT: Neuronal activity is energetically costly, but despite its importance, energy production and consumption have been studied in only a few neurone types. Neuroenergetics is of special importance in auditory brainstem nuclei, where neurones exhibit various biophysical adaptations for extraordinary temporal precision and show particularly high firing rates. We have studied the development of energy metabolism in three principal nuclei of the superior olivary complex (SOC) involved in precise binaural processing in the Mongolian gerbil (Meriones unguiculatus). We used immunohistochemistry to quantify metabolic markers for energy consumption (Na(+)/K(+)-ATPase) and production (mitochondria, cytochrome c oxidase activity and glucose transporter 3 (GLUT3)). In addition, we calculated neuronal ATP consumption for different postnatal ages (P0-90) based upon published electrophysiological and morphological data. Our calculations relate neuronal processes to the regeneration of Na(+) gradients perturbed by neuronal firing, and thus to ATP consumption by Na(+)/K(+)-ATPase. The developmental changes of calculated energy consumption closely resemble those of metabolic markers. Both increase before and after hearing onset occurring at P12-13 and reach a plateau thereafter. The increase in Na(+)/K(+)-ATPase and mitochondria precedes the rise in GLUT3 levels and is already substantial before hearing onset, whilst GLUT3 levels are scarcely detectable at this age. Based on these findings we assume that auditory inputs crucially contribute to metabolic maturation. In one nucleus, the medial nucleus of the trapezoid body (MNTB), the initial rise in marker levels and calculated ATP consumption occurs distinctly earlier than in the other nuclei investigated, and is almost completed by hearing onset. Our study shows that the mathematical model used is applicable to brainstem neurones. Energy consumption varies markedly between SOC nuclei with their different neuronal properties. Especially for the medial superior olive (MSO), we propose that temporally precise input integration is energetically more costly than the high firing frequencies typical for all SOC nuclei.
    Full-text · Article · Jun 2013 · PLoS ONE
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    • "Lateral olivocochlear (LOC) neurons, which are intermingled with principal cells in the LSO in gerbils (Kaiser et al. 2011) and mice (Sterenborg et al. 2010), have capacitance of only 50% compared with principal neurons (in our experiments, around 10 pF) and display a depolarized resting membrane potential, a delay-type firing pattern, and specific inward and outward current properties (Sterenborg et al. 2010). These criteria were used to exclude LOC neurons in the current-clamp mode. "
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    ABSTRACT: Interaural intensity differences are analyzed in neurons of the lateral superior olive (LSO) by integration of an inhibitory input from the medial nucleus of the trapezoid body (MNTB), activated by sound from the contralateral ear, with an excitatory input from the ipsilateral cochlear nucleus. The early postnatal refinement of this inhibitory MNTB-LSO projection along the tonotopic axis of the LSO has been extensively studied. However, little is known to what extent physiological changes at these inputs also occur after the onset of sound-evoked activity. Using whole-cell patch-clamp recordings of LSO neurons in acute brain stem slices, we analyzed the developmental changes of inhibitory synaptic currents evoked by MNTB fiber stimulation occurring after hearing onset. We compared these results in gerbils and mice, two species frequently used in auditory research. Our data show that neither the number of presumed input fibers nor the conductance of single fibers significantly changed after hearing onset. Also the amplitude of miniature inhibitory currents remained constant during this developmental period. In contrast, the kinetics of inhibitory synaptic currents greatly accelerated after hearing onset. We conclude that tonotopic refinement of inhibitory projections to the LSO is largely completed before the onset of hearing, whereas acceleration of synaptic kinetics occurs to a large part after hearing onset and might thus be dependent on proper auditory experience. Surprisingly, inhibitory input characteristics, as well as basic membrane properties of LSO neurons, were rather similar in gerbils and mice.
    Full-text · Article · Jun 2011 · Journal of Neurophysiology
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    ABSTRACT: A key requirement for encoding the auditory environment is the ability to dynamically alter cochlear sensitivity. However, merely attaining a steady state of maximal sensitivity is not a viable solution since the sensory cells and ganglion cells of the cochlea are prone to damage following exposure to loud sound. Most often, such damage is via initial metabolic insult that can lead to cellular death. Thus, establishing the highest sensitivity must be balanced with protection against cellular metabolic damage that can lead to loss of hair cells and ganglion cells, resulting in loss of frequency representation. While feedback mechanisms are known to exist in the cochlea that alter sensitivity, they respond only after stimulus encoding, allowing potentially damaging sounds to impact the inner ear at times coincident with increased sensitivity. Thus, questions remain concerning the endogenous signaling systems involved in dynamic modulation of cochlear sensitivity and protection against metabolic stress. Understanding endogenous signaling systems involved in cochlear protection may lead to new strategies and therapies for prevention of cochlear damage and consequent hearing loss. We have recently discovered a novel cochlear signaling system that is molecularly equivalent to the classic hypothalamic-pituitary-adrenal (HPA) axis. This cochlear HPA-equivalent system functions to balance auditory sensitivity and susceptibility to noise-induced hearing loss, and also protects against cellular metabolic insults resulting from exposures to ototoxic drugs. We review the anatomy, physiology, and cellular signaling of this system, and compare it to similar signaling in other organs/tissues of the body.
    Full-text · Article · Sep 2011 · Molecular Neurobiology
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