Probing Olfaction in Space and Time.

In this issue, Gill et al. apply holographic optogenetic stimulation in the olfactory bulb to control select neuronal ensembles in 3D. This approach allows them to dissociate the contribution of temporal spike features and spike rate to stimulus detection.

Cue-Evoked Dopamine Promotes Conditioned Responding during Learning.

Dopamine neurons mediate the association of conditioned stimuli (CS) with reward (unconditioned stimuli, US) by signaling the discrepancy between predicted and actual reward during the US. Some theoretical models suggest that learning is also influenced by the salience or associability of the CS. A hallmark of CS associability models is that they can explain latent inhibition, i.e., the observation that novel CS are more effectively learned than familiar CS. Novel CS are known to activate dopamine neurons, but whether those responses affect associative learning has not been investigated. Here, we used fiber photometry to characterize dopamine responses to inconsequential familiar and novel stimuli. Using bidirectional optogenetic modulation during conditioning, we then show that CS-evoked dopamine promotes conditioned responses. This suggests that Pavlovian conditioning is influenced by CS dopamine, in addition to US reward prediction errors. Accordingly, the absence of dopamine responses to familiar CS might explain their slower learning in latent inhibition.

Spontaneous Rapid Odor Source Localization Behavior Requires Interhemispheric Communication.

Navigation, finding food sources, and avoiding danger critically depend on the identification and spatial localization of airborne chemicals. When monitoring the olfactory environment, rodents spontaneously engage in active olfactory sampling behavior, also referred to as exploratory sniffing [1]. Exploratory sniffing is characterized by stereotypical high-frequency respiration, which is also reliably evoked by novel odorant stimuli [2, 3]. To study novelty-induced exploratory sniffing, we developed a novel, non-contact method for measuring respiration by infrared (IR) thermography in a behavioral paradigm in which novel and familiar stimuli are presented to head-restrained mice. We validated the method by simultaneously performing nasal pressure measurements, a commonly used invasive approach [2, 4], and confirmed highly reliable detection of inhalation onsets. We further discovered that mice actively orient their nostrils toward novel, previously unexperienced, smells. In line with the remarkable speed of olfactory processing reported previously [3, 5, 6], we find that mice initiate their response already within the first sniff after odor onset. Moreover, transecting the anterior commissure (AC) disrupted orienting, indicating that the orienting response requires interhemispheric transfer of information. This suggests that mice compare odorant information obtained from the two bilaterally symmetric nostrils to locate the source of the novel odorant. We further demonstrate that asymmetric activation of the anterior olfactory nucleus (AON) is both necessary and sufficient for eliciting orienting responses. These findings support the view that the AON plays an important role in the internostril difference comparison underlying rapid odor source localization.

Chronically reinforced, operant olfactory conditioning increases the number of newborn GABAergic olfactory periglomerular neurons in the adult rat.

The mammalian brain preserves the ability to replace olfactory periglomerular cells (PGC) throughout life. Even though we have detailed a great deal the mechanisms underlying stem and amplifying cells maintenance and proliferation, as well as those modulating migration and differentiation, our knowledge on PGC phenotypic plasticity is at best fragmented and controversial. Here we explored whether chronically reinforced olfactory conditioning influences the phenotype of newborn PGC. Accordingly, olfactory conditioned rats showed increased numbers of GAD 65/67 positive PGC. Because such phenotypic change was not accompanied neither by increments in the total number of PGC, or periglomerular cell nuclei labeled with bromodeoxyuridine, nor by reductions in the number of tyrosine hydroxylase (TH), calbindin (CB) or calretinin (CR) immunoreactive PGC, we speculate that increments in the number of GABAergic PGC occur at the expense of other PGC phenotypes. In any event, these results support that adult newborn PGC phenotype may be subjected to phenotypic plasticity influenced by sensory stimulation.