Using synaptophluorin to illuminate the modulation of sensory input to the mouse olfactory bulb

MCGANN, J.P.; GAINEY, M.A.; PÍREZ, N.; ELIAS, A.S.; MURATORE, C.; WACHOWIAK, M.

Cold Spring Harbor, New York, Estados Unidos.

Conferencia; Imaging neurons and neural activity: new methods, new result.; 2005

Cold Spring Harbor Laboratory

SynaptopHluorin (spH) expressed in mouse olfactory receptor neurons (ORNs) has recently been used to optically monitor odorant-evoked input from ORNs to the olfactory bulb in vivo (Bozza et al, Neuron 42:9-21). In the bulb, many homotypic ORN axons converge into anatomically discrete glomeruli. We exploited this organization to investigate feedback modulation of transmitter release from ORN terminals in olfactory bulb slices and in vivo. In slices, nerve shock-evoked spH signal magnitude was supralinearly related to the extracellular calcium concentration and linearly related to the amplitude of monosynaptic EPSCs. Paired nerve shocks revealed a strong and long-lasting paired-pulse suppression of spH signals that was partly relieved by glutamate receptor blockers and GABAB antagonists, indicating a feedback inhibition of transmitter release from ORNs. Stimulating some ORN axons innervating a glomerulus could suppress subsequente release from different, unstimulated fibers innervating the same glomerulus, thus demonstrating a strong heterosynaptic intraglomerular inhibition. Simultaneous presynaptic calcium imaging revealed that this inhibition is mediated partly by a downregulation of calcium influx through presynaptic N-type calcium channels. Blocking presynaptic inhibition in vivo with GABAB antagonist greatly increased the magnitude of odorant-evoked afferent input to the bulb. In addition to intraglomerular feedback inhibition, we also detected lateral presynaptic inhibition of neurotransmitter release by evoking spH in neighboring glomeruli in slices. This inhibition was much weaker than the feedback inhibition, however, and was limited at physiogical  temperatures. In vivo, activation of neighboring glomeruli with binary odorant mixtures did not suppress transmitter release relative to the corresponding single-odorant presentations. We conclude that intraglomerular feedback inhibition of transmitter release from ORNs can strongly modulate sensory input to the olfactory bulb, but lateral inhibition appears to play a relatively small role.