Kainate Receptors Play a Role in Modulating Synaptic Transmission in the Olfactory Bulb

Abstract

Glutamate is the neurotransmitter used at most excitatory synapses in the mammalian brain, including those in the olfactory bulb (OB). There, ionotropic glutamate receptors including N-methyl-d-aspartate receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) play a role in processes such as reciprocal inhibition and glomerular synchronization. Kainate receptors (KARs) represent another type of ionotropic glutamate receptor, which are composed of five (GluK1-GluK5) subunits. Whereas KARs appear to be heterogeneously expressed in the OB, evidence as to whether these KARs are functional, found at synapses, or modify synaptic transmission is limited. In the present study, coapplication of KAR agonists (kainate, SYM 2081) and AMPAR antagonists (GYKI 52466, SYM 2206) demonstrated that functional KARs are expressed by OB neurons, with a subset of receptors located at synapses. Application of kainate and the GluK1-selective agonist ATPA had modulatory effects on excitatory postsynaptic currents (EPSCs) evoked by stimulation of the olfactory nerve layer. Application of kainate and ATPA also had modulatory effects on reciprocal inhibitory postsynaptic currents (IPSCs) evoked using a protocol that evokes dendrodendritic inhibition. The latter finding suggests that KARs, with relatively slow kinetics, may play a role in circuits in which the relatively brief duration of AMPAR-mediated currents limits the role of AMPARs in synaptic transmission (e.g., reciprocal inhibition at dendrodendritic synapses). Collectively, our findings suggest that KARs, including those containing the GluK1 subunit, modulate excitatory and inhibitory transmission in the OB. These data further suggest that KARs participate in the regulation of synaptic circuits that encode odor information.

Mechanisms of zinc modulation of olfactory bulb AMPA receptors

“…The methods for preparing primary cultures of OB neurons have been previously described (Trombley and Blakemore, 1999;Blakemore et al, 2006;Blakemore et al, 2018). Briefly, the OBs were dissected from male and female postnatal days 0-4 (P0 to P4) Sprague-Dawley rat pups (Charles River, Wilmington, MA, USA), stripped of their meninges, cut into small pieces, and incubated for 1 hr at 37° C in a calcium-buffered papain solution (Worthington Biochemical, Lakewood, NJ, USA).…”

“…We used our previous morphological criteria (Trombley and Westbrook, 1990), which correspond well with our prior immunocytochemical/cell marker criteria (i.e., VGLUT1, GAD) (Blakemore et al, 2018), to identify presumptive M/T cells and interneurons in OB cultures. M/T cells were identified based on soma size (20 to 40 μm) and shape (pyramidal, multipolar) and were differentiated from the larger population of small-diameter (5-10 μm) interneurons based on soma size.…”

“…Previously described methods were used to obtain whole-cell patch-clamp recordings in cultured OB neurons Blakemore et al, 2006;Blakemore et al, 2018). Briefly, whole-cell voltage-clamp recordings were obtained from M/T cells at room temperature after cells had been in culture for 2 to 14 days.…”

Zinc Modulates Olfactory Bulb Kainate Receptors

“…We subsequently showed that KAR activation increases the frequency of excitatory spontaneous activity in OB interneurons, possibly by depolarizing mitral/tufted (M/T) cells closer to their threshold for spiking and enhancing glutamate release (Davila et al, 2007). Recently, we used combinations of KAR agonists and AMPAR antagonists to explore the distribution and circuit functions of KARs in the OB (Blakemore et al, 2018). Our findings suggest that a variety of OB neuron subtypes express functional KARs, which modulate excitatory and inhibitory transmission.…”

The Neurotransmitter Receptor Architecture of the Mouse Olfactory System

“…Sensory information is first processed in the main and accessory olfactory bulb via various neurotransmitters, either supplied directly by local interneurons of both, the main and accessory olfactory bulbs (main olfactory bulb: Murphy et al, 2004;Shepherd, 2004;Ennis et al, 2007;Linster and Cleland, 2016;Blakemore et al, 2018;Dong and Ennis, 2018; accessory olfactory bulb: Brennan et al, 1995;Dudley and Moss, 1995;Jia et al, 1999;Mohrhardt et al, 2018), via the horizontal limb of the diagonal band (GABAergic and cholinergic input; Brashear et al, 1986;Zaborszky et al, 1986) and the locus coeruleus (noradrenergic input; McLean et al, 1989). Several studies focused on the role of neurotransmitters in the olfactory system and showed that AMPARs/kainateRs and NMDARs regulate the excitability of mitral and tufted cells (Salin et al, 2001;Urban and Sakmann, 2002;Christie and Westbrook, 2006;Blakemore et al, 2018). Further, glutamatergic receptors play a role in vomeronasal stimulation in the glomeruli of the accessory olfactory bulb, enabling social and reproductive events (Dudley and Moss, 1995;Mohrhardt et al, 2018).…”