Deafness-related decreases in glycine-immunoreactive labeling in the rat cochlear nucleus

Abstract

There is increasing evidence of activity-related plasticity in auditory pathways. The present study examined the effects of decreased activity on immunolocalization of the inhibitory neurotransmitter glycine in the cochlear nucleus of the rat after bilateral cochlear ablation. Specifically, glycine-immunoreactive puncta adjacent to somatic profiles were compared in normal hearing animals and animals deafened for 14 days. The number of glycine-immunoreactive puncta surrounding somatic profiles of spherical and globular bushy cells, glycineimmunoreactive type I stellate multipolar cells, radiate neurons (type II stellate multipolar cells), and fusiform cells decreased significantly. In addition, the number of glycine immunopositive tuberculoventral (vertical or corn) cells in the deep layer of the dorsal cochlear nucleus also decreased significantly. These results suggest that decreased inhibition reported in cochlear nucleus after deafness may be due to decreases in glycine. Keywords hearing; auditory; ablation; neurotransmitterThere is increasing evidence of plasticity in the mature auditory system, with decreased activity from deafness or increased activity from noise overstimulation capable of inducing marked changes (recently reviewed by Syka, 2002). Activity-induced changes in the auditory brain stem range from changes in gene expression (e.g., Holt et al., 2005) to changes in neuronal response profiles (Francis and Manis, 2000). One of the most striking deafness-related changes in the auditory brain stem is a decrease in inhibition and an increase in spontaneous or evoked excitation, found in both the inferior colliculus (IC) and the cochlear nucleus (CN; Gerken, 1979;Willott and Lu, 1982;Bledsoe et al., 1995;Kaltenbach, 2000;Mossop et al., 2000;Salvi et al., 2000;Willott and Turner, 2000;© 2005 Wiley-Liss, Inc. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptShaddock Palombi et al., 2001), often leading to a change in the tonotopic map Nagase et al., 2000;Snyder et al., 2000). In the IC, the decreased inhibition seems associated with decreases in the inhibitory amino acid neurotransmitter γ-aminobutyric acid (GABA), with studies showing decreased GABA release (Bledsoe et al., 1995) and decreases in the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD) as well as GABA binding (Bauer et al., 2000;Milbrandt et al., 2000;Mossop et al., 2000;Caspary et al., 2002). In the CN, however, many studies suggest that glycine is the major inhibitory transmitter (Altschuler et al., 1986;Wu and Oertel, 1986;Caspary et al., 1987Caspary et al., , 1994Wenthold et al., 1987;Adams and Mugnaini, 1990;Bledsoe et al., 1990;Wickesberg and Oertel, 1990;Helfert et al., 1992;Kolston et al., 1992; Zook, 1992, 1999;Grothe and Sanes, 1993;Wickesberg et al., 1994;Wu and Kelly, 1994;Sato et al., 1995;Golding and Oertel, 1996;Juiz et al., 1996;Harty and Manis, 1998;Doucet et al., 1999;Godfrey et al., 2000;Zheng et al., 2000). Decreases in glycine-immunoreactive neurons and puncta (...

Age-Related Changes in the Inhibitory Response Properties of Dorsal Cochlear Nucleus Output Neurons: Role of Inhibitory Inputs

“…Age-related hearing loss can be thought of as a slow peripheral deafferentation, and the present findings are consistent with a number of partial deafferentation models using acoustic trauma, disarticulation, and, to a lesser extent, cochlear destruction (Suneja et al, 1998a,b;Milbrandt et al, 2000;Potashner et al, 2000;Brozoski et al, 2002;Asako et al, 2005). Aged rodents exhibit a number of age-related peripheral auditory changes, including a sloping lowfrequency loss of outer-hair cells and a small loss of apical and basal inner-hair cells (for review, see Willott, 1991;Saitoh et al, 1994;Gratton et al, 1996Gratton et al, , 1997Spongr et al, 1997;Ingham et al, 1999; and auditory nerve fiber loss (Keithley et al, 1989(Keithley et al, , 1992Dazert et al, 1996;Schmiedt et al, 1996).…”

Mechanisms contributing to central excitability changes during hearing loss

“…The reduced synaptic excitability in DCN FCs observed in the present study could therefore represent a first step in triggering homeostatic plastic adjustments that lead to hyperactivity and tinnitus (14,(64)(65)(66)(67). Hyperactivity related to tinnitus could result from a simultaneous reduction of AN-mediated transmission and an enhanced MS-mediated transmission (68) and/or a reduction in inhibitory synaptic transmission (58)(59)(60)67). Furthermore, the MS input excitability increase observed weeks after AOE (68) could represent a compensatory mechanism to counteract the initial MS-reduced excitability described in this paper.…”

“…After AOE, inhibition-mediated gain increases were absent following MS and AN stimulations, and this could be explained by the down-regulation of IPSPs recorded in FCs observed in both AN and MS synaptic pathways. A loss of inhibition was also observed following unilateral cochlear ablation (58,59), and a decrease in glycine receptor expression in the DCN after AOE has been previously reported (60). In vivo studies have shown reduced spontaneous activity in the DCN a few days after acoustic overexposure (61).…”

Noise-induced hearing loss: Neuropathic pain via Ntrk1 signaling

“…This suggests that the function of Vglut3 positive neurons in VCN might be strongly modulated by Gabrg3 or vice versa. However, the increase in Gabrg3 inhibitory receptor immunolabeling on putative glutamatergic-excitatory neurons expressing Slc17a6/ Slc17a8 could be interpreted as an effort to compensate for the loss of inhibitory glycinergic activity following deafening (Asako et al, 2005) and/or an attempt to suppress spontaneous or sound-evoked hyperactivity in the CN following acoustic trauma (Kaltenbach and McCaslin, 1996; Kaltenbach et al, 2000; Zhang and Kaltenbach, 1998). …”