Expression of AMPA-selective glutamate receptor subunits in morphologically defined neurons of the mammalian cochlear nucleus

Abstract

Glutamate and related amino acids mediate fast excitatory neurotransmission in the vertebrate CNS via ligand-gated cationic channels in the neuronal membrane. These channels are composed of different subunits that assemble into a functional receptor/channel complex. Although studies have shown that these subunits are differentially expressed in neurons, few studies have quantitatively addressed the cell-specific expression of glutamate subunits in relation to known glutamatergic pathways. In the vertebrate auditory system, glutamate is the proposed neurotransmitter of the auditory nerve and parallel fiber pathways. In situ hybridization histochemistry was used to localize AMPA-selective glutamate receptor subunit mRNAs in seven cell types of the rat cochlear nucleus. GluR1-GluR4 AMPA-selective subunits were all expressed in cochlear nucleus neurons; however, the subunits expressed in identified cells varied with the cell type. Granule cells, previously not known to receive glutamatergic input, expressed GluR2 and GluR4 subunits. Cartwheel and stellate interneurons in the dorsal cochlear nucleus, which receive parallel fiber input, expressed all four subunits. Neurons receiving synaptic input from the auditory nerve, including globular, round, spherical, and fusiform cells, expressed GluR2, GluR3, and GluR4 subunits. Furthermore, a subpopulation of round cells in the ventral cochlear nucleus, and fusiform cells in the dorsal cochlear nucleus, expressed the GluR3 subunit at greatly reduced levels compared to neighboring cells. The results confirm the auditory nerve and parallel fiber pathways as glutamatergic and identify a third synaptic population, projecting to granule cells, which is likely glutamatergic. The data suggest that the composition of GluR1-GluR4 subunits on neurons in the cochlear nucleus may be related to presynaptic input; moreover, heterogeneous patterns of expression of the GluR3 subunit, in addition, suggest that variability in mRNA levels within one population of morphologically defined cells is present.

Glutamate receptor subunit 2-selective antibody shows a differential distribution of calcium-impermeable AMPA receptors among populations of neurons

“…However, many brainstem neurons express mostly GluR3 and GluR4, e.g., in the thalamus (Sato et al, 1993b; this study). An example of preferential expression of GluR3 and GluR4 is in the anteroventral cochlear nucleus, where these subunits may be the major subunits in auditory synapses (Hunter et al, 1993;Wang et al, 1997;this study). In support of this, calcium-permeable AMPA receptors, presumably lacking GluR2, have been described in the avian cochlear nucleus (Otis et al, 1995).…”

Stoichiometries of AMPA receptor subunit mRNAs in rat brain fall into discrete categories

“…Although the present study did not map fractional concentrations in sensory areas projecting to these thalamic relays, there are reasons to expect that these also have AMPA receptors of the AR-2,3 type (i.e., enriched in GluR -3 and -4 relative to GluR1). In the auditory system, the spiral ganglion (Ryan et al, 1991;Safieddine and Eybalin, 1992;Niedzielski and Wenthold, 1995), cochlear nuclei (Hunter et al, 1993), and other auditory brainstem nuclei (Sato et al, 1993) are enriched in the GluR2, GluR3, and/or GluR4 subunits. The retina also has GluR2, GluR3, and GluR4 mRNA levels that are high relative to concentrations of GluR1 mRNA (Hamassaki-Britto et al, 1993).…”

Pathway-specific variants of AMPA receptors and their contribution to neuronal signaling

“…The particular subunits that compose this "fast" receptor are unknown. However, studies using in situ hybridization to identify the mRNA of various AMPA-receptor subunits in the cochlear nucleus of rats indicated that neurons innervated by the auditory nerve expressed GluR2, GIuR3, and GluR4, but not GluRl (Hunter et al, 1993;Sato et al, 1993). It will be interesting to determine whether this pattern of expression has any bearing on the rapidity of the response of AMPA receptors to glutamate.…”