Dopaminergic modulation of odor responses by local interneurons in the olfactory bulb

The olfactory bulb is one of the few regions in the brain where dopamine is provided locally by an intrinsic population of GABAergic interneurons but their role in processing of sensory information remains ambiguous. I examined the function of dopamine in processing of natural odors within the intact olfactory bulb of zebrafish by a combination of calcium-sensitive dye imaging and electrophysiological recordings in conjunction with traditional pharmacological manipulations and optogenetic stimulation. My results demonstrate that dopamine does not exert a prominent effect on olfactory nerve input. Instead, it directly modulates mitral cell properties by means of D2 receptors. Bath application of dopamine had a direct hyperpolarizing effect on mitral cells, resulting in an increase in neuronal response threshold and a suppression of spontaneous firing. As a direct consequence of the shift in response threshold, weak excitatory and inhibitory odor responses were abolished, whereas strong odor responses were enhanced. Therefore, the contrast within odor responses was enhanced, while the general pattern of activity remained rather stable. To directly analyze endogenous dopamine release I stimulated periglomerular cells using optogenetic tools. Experiments revealed a very slow dopaminergic effect that gradually built up over several seconds. It is therefore unlikely that dopamine directly participates in initial odor processing, but rather provides a mechanism to adapt the system to slow changes in the environment. Potential functions could be a channel-autonomous background subtraction or a global contrast enhancement.