In Vivo Modulation of Sensory Input to the Olfactory Bulb by Tonic and Activity-Dependent Presynaptic Inhibition of Receptor Neurons

Abstract

The first reorganization of odor representations in the nervous system occurs at the synapse between olfactory receptor neurons and second-order neurons in olfactory bulb glomeruli. Signal transmission at this synapse is modulated presynaptically by several mechanisms, a major one being mediated by GABA B receptors, which suppress presynaptic calcium influx and subsequent transmitter release from the receptor neuron terminal. Here, we imaged stimulus-evoked calcium influx into the receptor neuron terminal in anesthetized mice and used odorant and electrical stimulation combined with in vivo pharmacology to characterize the functional determinants of GABA B -mediated presynaptic inhibition and to test hypotheses on the role of this inhibition in olfactory processing. As expected from previous studies, blocking presynaptic GABA B receptors in vivo increased odorant-evoked presynaptic calcium signals, confirming that GABA B -mediated inhibition modulates the strength of receptor inputs. Surprisingly, we found that the strength of this inhibition was affected little by the nature of the input, being independent of the spatial distribution of activated glomeruli, independent of the sniff frequency used to sample the odorant, and similar for weak and strong odorant-evoked inputs. Instead, we found that tonic inhibition was a major determinant of receptor input strength; this tonic inhibition in turn was dependent on glutamatergic transmission from second-order neurons in the glomerular layer. Thus, rather than adaptively shaping odor representations in an activity-dependent manner, a primary role of presynaptic inhibition in vivo may be to modulate the magnitude of sensory input to the brain as a function of behavioral state.

Peripheral Adaptation Codes for High Odor Concentration in Glomeruli

“…Such tour de force is not necessary because reported ORN properties fully account for glomerular adaptation. In addition, our pharmacological experiments confirm the existence of a tonic presynaptic inhibition of ORN terminals (Petzold et al, 2008;Pírez and Wachowiak, 2008). They also show that at high odorant concentration, peripheral adaptation widely dominates evokedpresynaptic inhibition.…”

“…3C) also increased the overall signal [Ca 2ϩ area (a.u. )]: control, 22.86 Ϯ 2.15; CGP35348, 27.97 Ϯ 2.20; n ϭ 8; p ϭ 0.01), indicating that presynaptic tonic inhibition involved GABA B receptors (Pírez and Wachowiak, 2008). In contrast to presynaptic Ca 2ϩ signals, LFP responses were either maintained or slightly decreased (data not shown) on CGP35348, suggesting that GABA B receptors are involved at both presynaptic and postsynaptic sites, and their activation induces a complex modulation of the glomerular network activity.…”

“…It involves either a presynaptic inhibition of ORN terminals or an ORN adaptation at the nasal epithelium level. Presynaptic inhibition regulates glutamate release at ORN terminals (Hsia et al, 1999;Wachowiak and Cohen, 1999;Aroniadou-Anderjaska et al, 2000;Ennis et al, 2001;Olsen and Wilson, 2008) by decreasing Ca 2ϩ influx in the terminals (Wachowiak and Cohen, 1999;McGann et al, 2005;Vucinić et al, 2006;Pírez and Wachowiak, 2008). To investigate the role of presynaptic inhibition in glomerular adaptation, we tested the effects of local application of antagonists of ionotropic glutamate receptors and GABA B receptors on ORN terminals Ca 2ϩ responses.…”

“…In contrast, NBQX/D-APV reversibly enhanced presynaptic Ca 2ϩ responses evoked by both low and high odorant concentrations. Glutamate (Pírez and Wachowiak, 2008), that tonic presynaptic inhibition modulates odorant-evoked Ca 2ϩ signals in ORN terminals and as a consequence the glomerular output. Note that the increase of presynaptic Ca 2ϩ (area) by NBQX/D-APV was similar for odorant stimulations at low and high concentration (117 Ϯ 7% and 125 Ϯ 9%, respectively; p ϭ 0.54).…”

What Does Local Functional Hyperemia Tell about Local Neuronal Activation?

“…This phenomenon did not involve postsynaptic processing but resulted from a decrease of presynaptic Ca 2ϩ signals in ORN terminals and thus a decrease of the amount of glutamate released by these terminals. Because presynaptic GABA B receptors (Aroniadou-Anderjaska et al, 2000;Murphy and Isaacson, 2003;Vucinic et al, 2006;Pírez and Wachowiak, 2008), dopamine receptors (Hsia et al, 1999), or purinergic receptors (our unpublished observations) were not involved in the phenomenon (Lecoq et al, 2009), we could conclude that presynaptic Ca 2ϩ signal adaptation indirectly reflected peripheral adaptation. Figure 1, C and D, illustrates that, during such peripheral adaptation, the overall presynaptic Ca 2ϩ signal from ORNs and the vascular response uncoupled; during strong odor stimulation (Fig.…”