Modulation of gene expression in guinea pig paraflocculus after induction of hearing loss

Abstract

Hearing loss often results in plastic changes in the central auditory pathways, which may be involved in the generation of tinnitus, a phantom auditory sensation. However, although animal studies have consistently shown increased neural activity in auditory structures after hearing loss, tinnitus does not always develop. It has therefore been suggested that non-auditory structures perform a gating or regulatory role that determines whether the increased activity in auditory structures leads to conscious perception. Recent evidence points to the paraflocculus of the cerebellum as having such a role. Therefore, we investigated the early effects of hearing loss on gene expression in guinea pig paraflocculus. Gene expression was investigated after two weeks recovery from either acoustic or mechanical cochlear trauma. The genes investigated in our study were associated with inhibitory neurotransmission (GABA-A receptor subunit alpha 1; glutamate decarboxylase 1), excitatory neurotransmission (glutamate receptor NMDA subunit 1), and regulation of transmitter release (member of RAB family of small GTPase). Our results show increased mRNA levels of glutamate decarboxylase 1 in ipsilateral paraflocculus with no difference between the different methods of cochlear trauma. Early modulation of gene expression in the paraflocculus suggests that an early effect of hearing loss may affect the influence of this structure on auditory processing.

In vitro gentamicin exposure alters caveolae protein profile in cochlear spiral ligament pericytes

“…The specificity of Rab transport in hearing loss is slowly gaining interest and is still rather scattered. In a study assessing gene expression in guinea pig paraflocculus structure in the cerebellum after acoustic trauma, the protein Rab3A, which is involved in regulation of presynaptic neurotransmitter release, showed no changes [99]. A Mutation in the gene TBC1 Domain Family Member 24 (TBC1D24), encoding for a GTPase activating the proteins Rab5 and Rab35, involved in endosome to lysosome trafficking as a mechanism for degrading synaptic vesicles associated proteins, has been shown to cause severe neurodegeneration and deafness [100].…”

Influence of the paraflocculus on normal and abnormal spontaneous firing rates in the inferior colliculus

“…One of the non-auditory structures that shows hyperactivity after acoustic trauma and after development of tinnitus is the paraflocculus (PF) of the cerebellum (Brozoski et al, 2007). In addition, Mulders et al (2014a) showed altered mRNA levels of inhibitory genes in PF after cochlear trauma. Finally, other studies revealed that PF removal or silencing by glutamatergic antagonists or lidocaine resulted in reduced behaviours associated with tinnitus (Bauer et al, 2013a;Bauer et al, 2013b;Brozoski et al, 2013), whereas application of glutamatergic agonists induced tinnitus-like behaviour, which suggests a role for the PF as a modulator of tinnitus (Bauer et al, 2013b).…”