In vivo control of olfactory receptor neuron input to the olfactory bulb by presynaptic inhibition.

摘要

Presynaptic inhibition modulates signal transmission at the first synapse in the olfactory pathway by several mechanisms, a major one being mediated by GABAB receptors, which suppress presynaptic calcium influx and subsequent transmitter release from the receptor neuron terminal. Presynaptic inhibition could function to limit the strength of olfactory input to the central nervous system, as well as provide a substrate for centrifugal control of odorant representations early in the olfactory system.;To address these questions I imaged stimulus-evoked calcium influx into the receptor neuron terminal in anesthetized mice, as well as neurotransmitter release in anesthetized and awake behaving mice. Odorant and electrical stimulation combined with in vivo pharmacology were used to characterize the functional determinants of GABAB-mediated presynaptic inhibition and to test hypotheses on the role of this inhibition in olfactory processing, and to study the temporal dynamics of olfactory receptor neuron input. Blocking presynaptic GABAB receptors in vivo increased the amplitude of odorant-evoked input to glomeruli, confirming that GABA B-mediated inhibition modulates the strength of receptor inputs. The strength of this inhibition was affected little by the nature of the input, being independent of the sniff frequency used to sample the odorant, and similar for weak and strong odorant-evoked inputs. Tonic inhibition was a major determinant of receptor input strength; and was dependent on glutamatergic transmission from second-order neurons in the glomerular layer.;Odorant-evoked responses in awake behaving mice were smaller in amplitude and more variable than in anesthetized preparations. When the behavioral state of the awake animal was altered by presenting novel stimuli or changing the valence of the stimulus, odorant-evoked responses were affected. Responses were also affected in the awake animal by systemic GABAB receptor blockade. Taken together these results suggest that tonic inhibition via top-down, centrifugal control plays a major role in modulating the magnitude of sensory input to the brain as a function of behavioral state.