GABAB receptors are G-protein coupled receptors for the inhibitory neurotransmitter GABA. Functional GABAB receptors are formed as heteromers of GABAB1 and GABAB2 subunits, which further associate with various regulatory and signaling proteins to provide receptor complexes with distinct pharmacological and physiological properties. GABAB receptors are widely distributed in nervous tissue, where they are involved in a number of processes and in turn are subject to a number of regulatory mechanisms. In this review, we summarize current knowledge of the cellular distribution and function of the receptors in the inner ear and auditory pathway of the mammalian brainstem and midbrain. The findings suggest that in these regions, GABAB receptors are involved in processes essential for proper auditory function, such as cochlear amplifier modulation, regulation of spontaneous activity, binaural and temporal information processing, and predictive coding. Since impaired GABAergic inhibition has been found to be associated with various forms of hearing loss, GABAB dysfunction could also play a role in some pathologies of the auditory system.

• Keywords
• GABAB receptor, auditory, hearing loss, neuronal excitability, synaptic transmission, tinnitus,
• MeSH
• Cell Membrane MeSH
• gamma-Aminobutyric Acid MeSH
• Deafness * MeSH
• Cognition MeSH
• Receptors, GABA-B * MeSH
• Mammals MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• gamma-Aminobutyric Acid MeSH
• Receptors, GABA-B * MeSH

The physiological functions of glycine receptors (GlyRs) depend on their subcellular locations. In axonal terminals of the central neurons, GlyRs trigger a slow facilitation of presynaptic transmitter release; however, their spatial relationship to the release sites is not known. In this study, we examined the distribution of GlyRs in the rat glutamatergic calyx of Held nerve terminal using high-resolution pre-embedding immunoelectron microscopy. We performed a quantitative analysis of GlyR-associated immunogold (IG) labeling in 3D reconstructed calyceal segments. A variable density of IG particles and their putative accumulations, inferred from the frequency distribution of inter-IG distances, indicated a non-uniform distribution of the receptors in the calyx. Subsequently, increased densities of IG particles were found in calyceal swellings, structures characterized by extensive exocytosis of glutamate. In swellings as well as in larger calyceal stalks, IG particles did not tend to accumulate near the glutamate releasing zones. On the other hand, GlyRs in swellings (but not in stalks) preferentially occupied membrane regions, unconnected to postsynaptic cells and presumably accessible by ambient glycine. Furthermore, the sites with increased GlyR concentrations were found in swellings tightly juxtaposed with GABA/glycinergic nerve endings. Thus, the results support the concept of an indirect mechanism underlying the modulatory effects of calyceal GlyRs, activated by glycine spillover. We also suggest the existence of an activity-dependent mechanism regulating the surface distribution of α homomeric GlyRs in axonal terminals of central neurons.

• Keywords
• MNTB, calyx of Held, glycine receptor, pre-embedding immunoelectron microscopy, presynaptic, spillover,
• MeSH
• gamma-Aminobutyric Acid metabolism   MeSH
• Glycine metabolism   MeSH
• Rats MeSH
• Brain Stem cytology   MeSH
• Statistics, Nonparametric MeSH
• Neurons cytology   MeSH
• Rats, Wistar MeSH
• Presynaptic Terminals metabolism   ultrastructure   MeSH
• Receptors, Glycine metabolism   ultrastructure   MeSH
• Synapses metabolism   ultrastructure   MeSH
• In Vitro Techniques MeSH
• Vesicular Glutamate Transport Protein 1 metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• gamma-Aminobutyric Acid MeSH
• Glycine MeSH
• Receptors, Glycine MeSH
• Vesicular Glutamate Transport Protein 1 MeSH