Expression of AMPA receptor subunit flip/flop splice variants in the rat auditory brainstem and inferior colliculus

Abstract

The expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunit mRNAs and their flip/flop splice variants was evaluated in the rat auditory brainstem and inferior colliculus employing in situ hybridization with radiolabeled oligonucleotide probes. A differential expression of AMPA receptor subunits in auditory nuclei was observed. In general, neurons in all nuclei of the auditory brainstem express high levels of GluR-C flop and GluR-D flop mRNA, but low to very low levels of GluR-A and GluR-B mRNA. The strongest GluR-C and -D flop expression is found in the ventral and medial part of the anteroventral cochlear nucleus, the posteroventral cochlear nucleus, and the medial and the lateral superior olive. These nuclei are part of the binaural auditory pathway which is important for sound localization in space. In contrast, neurons in the central nucleus of the inferior colliculus express high levels of GluR-B flip but only low levels of the other AMPA receptor subunits. From our data, we conclude that neurons of nuclei involved in binaural processing exhibit a specific "auditory AMPA receptor" which consists primarily of GluR-C flop and -D flop and often lacks GluR-B subunits; this indicates fast kinetics and high Ca(2+) permeability of AMPA receptor currents. In contrast, neurons in the central nucleus of the inferior colliculus contain large amounts of GluR-B flip subunits resulting in Ca(2+) impermeable AMPA receptors with slow kinetics.

Acoustic trauma slows AMPA receptor‐mediated EPSCs in the auditory brainstem, reducing GluA4 subunit expression as a mechanism to rescue binaural function

“…), and these receptor subunits are predominantly flop spiced variants (Schmid et al . ). Although the EPSC decay kinetics in the MNTB (∼0.4 ms) (Taschenberger & von Gersdorff, ; Futai et al .…”

“…AMPAR-mediated EPSCs with fast kinetics are widely expressed in the auditory pathway, driving high-fidelity neurotransmission in birds and mammals (Raman & Trussell, 1992;Barnes-Davies & Forsythe, 1995;Golding et al 1995;Otis et al 1995;Gardner et al 1999Gardner et al , 2001Trussell, 1999;Joshi et al 2004;Koike-Tani et al 2005Steinert et al 2010). Expression studies show that EPSCs exhibiting rapid kinetics are associated with GluA4-containing AMPARs (Mosbacher et al 1994;Geiger et al 1995;Lambolez et al 1996), which are broadly expressed in the auditory brainstem (Rubio & Wenthold, 1999;Yang et al 2011), and these receptor subunits are predominantly flop spiced variants (Schmid et al 2001). Although the EPSC decay kinetics in the MNTB (ß0.4 ms) (Taschenberger & von Gersdorff, 2000;Futai et al 2001;Fernandez-Chacon et al 2004;Postlethwaite et al 2007) are somewhat faster than in the LSO (ß0.7 ms), the prevalence of GluA4 mRNA in the LSO is consistent with the observed fast EPSC decay kinetics.…”

Impaired auditory processing and altered structure of the endbulb of Held synapse in mice lacking the GluA3 subunit of AMPA receptors

“…It has been proposed that the subunit composition of postsynaptic AMPARs determines the functional differences in auditory neurons (Geiger et al, 1995). However this hypothesis seems to be more complex because the CN and the SOC have in common the highest levels of the fast kinetics GluA3- and GluA4 AMPAR subunits, as compared to the levels of GluA1 and GluA2 (Koike-Tani et al, 2005; Petralia et al, 2000; Schmid et al, 2001; Wang et al, 1998). Regardless the similarity of AMPAR subunit composition, it is clear that the CN and the SOC respond differentially to changes in the acoustic environment.…”

Synaptic integration in dendrites: exceptional need for speed

“…mEPSCs are large and fast in octopus and MSO cells (750–900 pS, decay time constants 215–325 μs at 33–36°C)(Gardner et al 1999; Cao et al 2008). AMPA receptors include the rapidly gating flop variants of GluA4 subunits, perhaps with GluA3 (Caicedo & Eybalin, 1999; Gardner et al 1999, 2001; Schmid et al 2001; Yang et al 2011). EPSCs evoked in octopus cells by stimulating the fibre bundle rise over ∼0.5 ms and fall with decay time constants ∼0.7 ms (Cao & Oertel, 2010).…”