The serotonergic raphe nuclei have been implicated in regulating neural circuits that produce nearly all types of behavior, including cognitive, motor and social, and are strongly linked to slower timescale changes in mood and mental health. However, increasing evidence suggests that the raphe nuclei are capable of broadcasting phasic, temporally precise signals that regulate information processing on fast, subsecond timescales. Projections from the raphe nuclei terminate throughout the brain and influence neural processing even in early sensory areas. On page 271, Kapoor and colleagues demonstrate that phasic raphe nuclei activation leads to rapid changes in odor coding in the olfactory system. As depicted in the image of the tortoise and the hare (right), these data support the emerging notion that the raphe nuclei affect information processing at multiple timescales.

The olfactory bulb processes incoming odor signals, performing operations that include normalization and contrast enhancement, before sending information to downstream regions via mitral and tufted cell axons. Using two-photon imaging of mitral and tufted cells in vivo, the authors show that activation of raphe nuclei triggers distinct changes in these olfactory bulb output channels. Raphe stimulation sensitized tufted cells, generally enhancing odor-driven activity. On the other hand, it led to bidirectional modulation of mitral cell responses, which improved pattern separation of similar odors. The distinct effects on tufted versus mitral cells provide strong clues to functional differences between the two olfactory bulb output channels. Although the authors did not examine behavioral consequences in this study, it is tempting to speculate that these effects would simultaneously improve odor detection and discrimination.

Through an elegant series of in vitro electrophysiology, optogenetics and pharmacology experiments, the authors next dissected the cellular and synaptic mechanisms underlying the rapid changes in odor coding. They found that raphe activation exerted both excitatory and inhibitory influences on mitral and tufted cells through dual release of glutamate and serotonin, respectively. Notably, the inhibitory effects of raphe activation were polysynaptic, suggesting that serotonin may exert its direct influence on GABAergic microcircuits in the bulb.

In summary, the authors demonstrated that raphe nuclei activation regulates early olfactory information processing on a subsecond timescale through dual release of glutamate and serotonin in the olfactory bulb. Beyond the olfactory bulb, the raphe nuclei exert control over widely distributed brain networks. It will be critical for future work to examine how these rapid changes in sensory processing are coordinated with modulation of other brain networks, including regions involved in affect and reward processing.