Presynaptic Muscarinic Receptors Enhance Glutamate Release at the Mitral/Tufted to Granule Cell Dendrodendritic Synapse in the Rat Main Olfactory Bulb

Abstract

The mammalian olfactory bulb receives multiple modulatory inputs, including a cholinergic input from the basal forebrain. Understanding the functional roles played by the cholinergic input requires an understanding of the cellular mechanisms it modulates. In an in vitro olfactory bulb slice preparation we demonstrate cholinergic muscarinic modulation of glutamate release onto granule cells that results in gamma-aminobutyric acid (GABA) release onto mitral/tufted cells. We demonstrate that the broad-spectrum cholinergic agonist carbachol triggers glutamate release from mitral/tufted cells that activates both AMPA and NMDA receptors on granule cells. Activation of the granule cell glutamate receptors leads to calcium influx through voltage-gated calcium channels, resulting in spike-independent, asynchronous GABA release at reciprocal dendrodendritic synapses that granule cells form with mitral/tufted cells. This cholinergic modulation of glutamate release persists through much of postnatal bulbar development, suggesting a functional role for cholinergic inputs from the basal forebrain in bulbar processing of olfactory inputs and possibly in postnatal development of the olfactory bulb.

Somatostatin Contributes toIn VivoGamma Oscillation Modulation and Odor Discrimination in the Olfactory Bulb

“…As sst2 receptors are localized in mitral cell dendrites, sst2 activation could decrease mitral-to-granule cell glutamate release and consequently decrease GABA release from granule cells. Indeed, the increase of the conditioning response observed after blocking sst2 receptors supports an increase excitatory drive on granule cells that, in turn, could activate inhibitory synaptic transmission, as reported for acetylcholine (Ghatpande and Gelperin, 2009). In other brain regions, presynaptic modulation of glutamate release by sst2 receptors results from the inhibition of voltage-gated calcium channels (VGCC) or from the activation of specific potassium channels such as A-type channels (I A ) (Baraban and Tallent, 2004;Viollet et al, 2008).…”

“…In vitro, cholinergic transmission excites mitral cells and inhibits granule cells (Castillo et al, 1999;Ghatpande and Gelperin, 2009). In vivo pharmacological blockade of cholinergic tone is associated with changes in gamma oscillations (Tsuno et al, 2008), odor receptive fields of mitral cells, and olfactory behavior (Chaudhury et al, 2009).…”

Muscarinic receptor type 1 (M1) stimulation, probably through KCNQ/Kv7 channel closure, increases spontaneous GABA release at the dendrodendritic synapse in the mouse accessory olfactory bulb

“…Possibly, as reported in the olfactory bulb (Ghatpande et al, 2009), carbachol acts on mitral cells to stimulate their glutamate release, which then stimulate GABA release by granule cells. A role of periglomerular cells (another GABA neuron in AOB) was not ruled out but is less likely because cholinergic fibres are not seen in the periglomerular layer (Carson and Burd, 1980).…”

The Olfactory System

“…On the one hand, infusion of ACh into MOB reduced paired-pulse depression of LOT-evoked GCL field potentials via muscarinic receptor-mediated inhibition of GC GABA release (Elaagouby et al, 1991). On the other hand, muscarinic receptor activation has been shown to presynaptically enhance GC GABA release (Castillo et al, 1999;Ghatpande and Gelperin, 2009) and, separately, to increase GC excitability in the MOB and AOB by enhancing afterdepolarizations Smith and Araneda, 2010). Enhancement of afterdepolarizations might attenuate GC spike adaptation across repetitive MTC synaptic input and increase inhibition of MTCs to repetitive stimulation as during high frequency sniffing.…”