NMDA Receptor-Dependent Synaptic Activation of TRPC Channels in Olfactory Bulb Granule Cells

Abstract

TRPC channels are widely expressed throughout the nervous system including the olfactory bulb where their function is largely unknown. Here we describe their contribution to central synaptic processing at the reciprocal mitral and tufted cell - granule cell microcircuit, the most abundant synapse of the mammalian olfactory bulb. Suprathreshold activation of the synapse causes sodium action potentials in mouse granule cells and a subsequent long-lasting depolarization (LLD) linked to a global dendritic postsynaptic calcium signal recorded with two-photon laser scanning microscopy. These signals are not observed after action potentials evoked by current injection in the same cells. The LLD persists in the presence of group I metabotropic glutamate receptor antagonists but is entirely absent from granule cells deficient for the NMDA receptor subunit NR1. Moreover, both depolarization and Ca2+ rise are sensitive to the blockade of NMDA receptors. The LLD and the accompanying Ca2+ rise are also absent in granule cells from mice deficient for both TRPC channel subtypes 1 and 4, whereas the deletion of either TRPC1 or TRPC4 results in only a partial reduction of the LLD. Recordings from mitral cells in the absence of both subunits reveal a reduction of asynchronous neurotransmitter release from the granule cells during recurrent inhibition. We conclude that TRPC1 and TRPC4 can be activated downstream of NMDA receptor activation and contribute to slow synaptic transmission in the olfactory bulb, including the calcium dynamics required for asynchronous release from the granule cell spine.

Trpc1

“…In agreement with this idea, compound mice lacking Trpc1 and Trpc4 lacked epileptiform bursting secondary to metabotropic glutamate receptor activation in hippocampal CA1 neurons (Phelan et al 2013) or suppressed by 74 % in lateral septal neurons in single Trpc1 mutant mice (Phelan et al 2012). Similar effects were seen in olfactory granule cells (Stroh et al 2012). Following previous cell culture work (Ma et al 2003), Ong et al showed that TRPC1-enhanced store-operated currents in myeloid precursors and mice lacking Trpc1 showed a modest decrease in osteoclastogenesis and an increase in bone mass (Ong et al 2013).…”

Serotonin increases synaptic activity in olfactory bulb glomeruli

“…In the lateral geniculate nucleus, 5HT activates TRPC4 channels, causing sufficient calcium influx to mediate action potential-independent GABA release (Munsch et al 2003). TRPC channels are also involved in action potential-independent signaling at dendrodendritic synapses between granule and MCs (Stroh et al 2012). Thus TRP-mediated mechanisms may be a common target of neuromodulator transmitter action at dendrodendritic synapses.…”

Transient Receptor Potential Channels and Their Role in Modulating Radial Glial–Neuronal Interaction: A Signaling Pathway Involving mGluR5

“…Our interest in elucidating the function of TRPC channels in neural progenitor migration as well as the current lack of specific channel blockers for the TRPCs led us to use TRPCdeficient C57 mice. TRPC1/TRPC4/TRPC5-deficient mice (1/ 4/5 TKO) [24] and TRPC3/TRPC6-deficient mice (3/6 DKO) have been described [25]. All TRPC-deficient mice were from a mixed C57 genetic background.…”