Evidence for Ca²⁺-permeable AMPA receptors in the olfactory bulb

Abstract

alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs), a subtype of glutamate receptor, contribute to olfactory processing in the olfactory bulb (OB). These ion channels consist of various combinations of the subunits GluR1-GluR4, which bestow certain properties. For example, AMPARs that lack GluR2 are highly permeable to Ca(2+) and generate inwardly rectifying currents. Because increased intracellular Ca(2+) could trigger a host of Ca(2+)-dependent odor-encoding processes, we used whole cell recording as well as histological and immunocytochemical (ICC) techniques to investigate whether AMPARs on rat OB neurons flux Ca(2+). Application of 1-naphthylacetyl spermine (NAS), a selective antagonist of Ca(2+)-permeable AMPARs (CP-AMPARs), inhibited AMPAR-mediated currents in subsets of interneurons and principal cells in cultures and slices. The addition of spermine to the electrode yielded inwardly rectifying current-voltage plots in some cells. In OB slices, olfactory nerve stimulation elicited excitatory responses in juxtaglomerular and mitral cells. Bath application of NAS with d,l-2-amino-5-phosphonovaleric acid (AP5) to isolate AMPARs suppressed the amplitudes of these synaptic responses compared with responses obtained using AP5 alone. Co(2+) staining, which involves the kainate-stimulated influx of Co(2+) through CP-AMPARs, produced diverse patterns of labeling in cultures and slices as did ICC techniques used with a GluR2-selective antibody. These results suggest that subsets of OB neurons express CP-AMPARs, including functional CP-AMPARs at synapses. Ca(2+) entry into cells via these receptors could influence odor encoding by modulating K(+) channels, N-methyl-d-aspartate receptors, and Ca(2+)-binding proteins, or it could facilitate synaptic vesicle fusion.

Calcium permeable AMPA receptors and autoreceptors in external tufted cells of rat olfactory bulb

“…Similar data were obtained from 3 rats, using 2 olfactory bulb slices for each condition (stimulus and two controls). These data confirm results obtained from juxtaglomerular cells in another recent study (Blakemore et al, 2006), and they provide further support for the expression of calcium permeable AMPA receptors in neurons of the glomerular layer. …”

“…A recent study using cultured cells and slices reported direct evidence for the expression of calcium permeable AMPA receptors in olfactory bulb neurons. In the glomerular layer of slices, unidentified neurons (collectively termed juxtaglomerular cells) were found to take up Co 2+ ions (which selectively permeate calcium permeable AMPA receptors) and their postsynaptic responses to olfactory nerve shock were blocked by 1-naphthyl acetyl-spermine (NAS), a selective antagonist of calcium permeable AMPA receptors (Blakemore et al, 2006).…”

“…A recent study using cultured cells and slices reported direct evidence for the expression of calcium permeable AMPA receptors in olfactory bulb neurons. In the glomerular layer of slices, unidentified neurons (collectively termed juxtaglomerular cells) were found to take up Co 2+ ions (which selectively permeate calcium permeable AMPA receptors) and their postsynaptic responses to olfactory nerve shock were blocked by 1-naphthyl acetyl-spermine (NAS), a selective antagonist of calcium permeable AMPA receptors (Blakemore et al, 2006).In our study, we specifically targeted ET cells in slices for electrophysiological and optical recording to determine if they expressed calcium permeable AMPA receptors. We examined the pharmacology and voltage dependence of excitatory postsynaptic currents (EPSCs) activated either by glutamate released from olfactory nerve terminals, or by exogenously applied glutamate.…”

“…However, 300 μM NAS was required to block Co 2+ and Zn 2+ entry into hippocampal neurons in slices and in culture (Yin et al, 2002;Ogoshi and Weiss, 2003), and it was also used to block currents in excised patches (Jia et al, 2002). In the olfactory bulb, Blakemore et al (2006) reported that 10 μM NAS was sufficient to attenuate the olfactory nerve shock-evoked EPSC in a sample of juxtaglomerular cells, which might have included ET cells. In our hands, 100 μM bath perfusion did not appreciably diminish the mean EPSC amplitude of ET cells relative to a group of control cells.…”

Topological Regulation of Synaptic AMPA Receptor Expression by the RNA-Binding Protein CPEB3

“…They also exhibit a characteristic facilitation due to an activity-dependent polyamine unblock that occurs during a train of synaptic activity and which enhances the ability of excitatory postsynaptic potentials to evoke action potentials (APs) (Rozov and Burnashev, 1999; Savtchouk and Liu, 2011). GluA2 expression in neurons varies considerably with low GluA2 levels in a wide variety of neurons that display tonic activity, such as olfactory neurons, glutamatergic neurons in the lateral habenula, neostriatal cholinergic interneurons, auditory neurons in the deep cerebellar nucleus and GABAergic interneurons in several brain regions (Blakemore et al, 2006; Li et al, 2011; Liu and Cull-Candy, 2000; Maroteaux and Mameli, 2012; Samoilova et al, 1999). These Ca-permeable AMPARs play a critical role in the induction of NMDAR-independent synaptic plasticity, modulation of membrane excitability and long-range gamma oscillations (Liu and Zukin, 2007).…”