Sniffing and presynaptic inhibition of receptor input to the olfactory bulb: tonic versus feedback inhibition

PÍREZ, N.; WACHOWIAK, M.

San Diego, California, Estados Unidos

Conferencia; Reunion Anual de Society for Neuroscience; 2007

Society for Neuroscience

Olfactory receptor neurons (ORNs) converge onto glomeruli in the olfactory bulb (OB). We and others have shown that ORN input to the OB is modulated by presynaptic inhibition at the ORN axon terminal. In mouse OB slice preparations, this inhibition operates primarily in an intraglomerular feedback mode, with a single olfactory nerve (ON) shock evoking GABAB receptor-mediated inhibition of subsequent inputs to the same glomerulus. Here, we ask how sniffing affects presynaptic inhibition of ORN inputs by imaging calcium influx into ORN terminals, using different stimulation paradigms designed to mimic sniffing in the behaving animal. First, we asked whether sniff frequency affects the strength of presynaptic inhibition. In slices, feedback inhibition is strongest ~100 ms after a conditioning shock and decays with a time constant of ~500 ms. Sniff frequency in rodents varies from ~1.5 Hz (750 ms inter-sniff interval) to ~10 Hz (100 ms inter-sniff interval); we thus hypothesized that, in vivo, sniff frequency would affect the strength of presynaptic inhibition. We imaged odorant-evoked input to glomeruli using an artificial sniff paradigm and blocked presynaptic inhibition with the GABAB receptor antagonist CGP35348. Surprisingly, the strength of presynaptic inhibition did not change over sniff frequencies ranging from 1 - 5 Hz. In fact, even the response to the first sniff after odorant onset was subject to significant presynaptic inhibition. One explanation for this result is that presynaptic inhibition occurs tonically in vivo. Indeed, with paired ON shocks delivered in vivo, CGP35348 increased conditioning response amplitude, indicating a tonic inhibition not seen in slices. We next asked how the temporal dynamics of input evoked by a single sniff (consisting of a 150 - 200 ms burst of ORN firing) affects presynaptic inhibition. To separate the contributions of feedback versus tonic inhibition, we used a nerve shock protocol (?electrical sniffing?) designed to generate input dynamics similar to those evoked by an actual sniff. Responses to an electrical sniff in vivo were increased by CGP35348, similar to the effect observed with odorant-evoked responses. In contrast, in OB slices (which lack tonic inhibition), CGP55845 had no effect on the response to a single electrical sniff. Thus, while synchronous activation of ORN inputs evoked by a single ON shock elicits strong feedback inhibition, the slower, asynchronous dynamics of ORN input elicited during sniffing may fail to do so. Instead, tonic inhibition may be the dominant factor regulating the strength of ORN input to the OB in the intact animal.