Organization and engagement of a prefrontal-olfactory network during olfactory selective attention.

BACKGROUND: Sensory perception is profoundly shaped by attention. Attending to an odor strongly regulates if and how it is perceived - yet the brain systems involved in this process are unknown. Here we report integration of the medial prefrontal cortex (mPFC), a collection of brain regions integral to attention, with the olfactory system in the context of selective attention to odors. METHODS: First, we used tracing methods to establish the tubular striatum (TuS, also known as the olfactory tubercle) as the primary olfactory region to receive direct mPFC input in rats. Next, we recorded (i) local field potentials from the olfactory bulb (OB), mPFC, and TuS, or (ii) sniffing, while rats completed an olfactory selective attention task. RESULTS: Gamma power and coupling of gamma oscillations with theta phase were consistently high as rats flexibly switched their attention to odors. Beta and theta synchrony between mPFC and olfactory regions were elevated as rats switched their attention to odors. Finally, we found that sniffing was consistent despite shifting attentional demands, suggesting that the mPFC-OB theta coherence is independent of changes in active sampling. CONCLUSIONS: Together, these findings begin to define an olfactory attention network wherein mPFC activity, as well as that within olfactory regions, are coordinated based upon attentional states.

Selective Attention Controls Olfactory Decisions and the Neural Encoding of Odors.

Critical animal behaviors, especially among rodents, are guided by odors in remarkably well-coordinated manners, yet many extramodal sensory cues compete for cognitive resources in these ecological contexts. That rodents can engage in such odor-guided behaviors suggests that they can selectively attend to odors. Indeed, higher-order cognitive processes-such as learning, memory, decision making, and action selection-rely on the proper filtering of sensory cues based on their relative salience. We developed a behavioral paradigm to reveal that rats are capable of selectively attending to odors in the presence of competing extramodal stimuli. We found that this selective attention facilitates accurate odor-guided decisions, which become further strengthened with experience. Further, we uncovered that selective attention to odors adaptively sharpens their representation among neurons in the olfactory tubercle, an olfactory cortex region of the ventral striatum that is considered integral for evaluating sensory information in the context of motivated behaviors. Odor-directed selective attention exerts influences during moments of heightened odor anticipation and enhances odorant representation by increasing stimulus contrast in a signal-to-noise-type coding scheme. Together, these results reveal that rats engage selective attention to optimize olfactory outcomes. Further, our finding of attention-dependent coding in the olfactory tubercle challenges the notion that a thalamic relay is integral for the attentional control of sensory coding.

Preservation of Essential Odor-Guided Behaviors and Odor-Based Reversal Learning after Targeting Adult Brain Serotonin Synthesis.

The neurotransmitter serotonin (5-HT) is considered a powerful modulator of sensory system organization and function in a wide range of animals. The olfactory system is innervated by midbrain 5-HT neurons into both its primary and secondary odor-processing stages. Facilitated by this circuitry, 5-HT and its receptors modulate olfactory system function, including odor information input to the olfactory bulb. It is unknown, however, whether the olfactory system requires 5-HT for even its most basic behavioral functions. To address this question, we established a conditional genetic approach to specifically target adult brain tryptophan hydroxylase 2 (Tph2), encoding the rate-limiting enzyme in brain 5-HT synthesis, and nearly eliminate 5-HT from the mouse forebrain. Using this novel model, we investigated the behavior of 5-HT-depleted mice during performance in an olfactory go/no-go task. Surprisingly, the near elimination of 5-HT from the forebrain, including the olfactory bulbs, had no detectable effect on the ability of mice to perform the odor-based task. Tph2-targeted mice not only were able to learn the task, but also had levels of odor acuity similar to those of control mice when performing coarse odor discrimination. Both groups of mice spent similar amounts of time sampling odors during decision-making. Furthermore, odor reversal learning was identical between 5-HT-depleted and control mice. These results suggest that 5-HT neurotransmission is not necessary for the most essential aspects of olfaction, including odor learning, discrimination, and certain forms of cognitive flexibility.

Odor- and state-dependent olfactory tubercle local field potential dynamics in awake rats.

The olfactory tubercle (OT), a trilaminar structure located in the basal forebrain of mammals, is thought to play an important role in olfaction. While evidence has accumulated regarding the contributions of the OT to odor information processing, studies exploring the role of the OT in olfaction in awake animals remain unavailable. In the present study, we begin to address this void through multiday recordings of local field potential (LFP) activity within the OT of awake, freely exploring Long-Evans rats. We observed spontaneous OT LFP activity consisting of theta- (2-12 Hz), beta- (15-35 Hz) and gamma- (40-80 Hz) band activity, characteristic of previous reports of LFPs in other principle olfactory structures. Beta- and gamma-band powers were enhanced upon odor presentation. Simultaneous recordings of OT and upstream olfactory bulb (OB) LFPs revealed odor-evoked LFP power at statistically similar levels in both structures. Strong spectral coherence was observed between the OT and OB during both spontaneous and odor-evoked states. Furthermore, the OB theta rhythm more strongly cohered with the respiratory rhythm, and respiratory-coupled theta cycles in the OT occurred following theta cycles in the OB. Finally, we found that the animal's internal state modulated LFP activity in the OT. Together, these data provide initial insights into the network activity of the OT in the awake rat, including spontaneous rhythmicity, odor-evoked modulation, connectivity with upstream sensory input, and state-dependent modulation.

Encoding and representation of intranasal CO2 in the mouse olfactory cortex.

Intranasal trigeminal sensory input, often perceived as a burning, tingling, or stinging sensation, is well known to affect odor perception. While both anatomical and functional imaging data suggest that the influence of trigeminal stimuli on odor information processing may occur within the olfactory cortex, direct electrophysiological evidence for the encoding of trigeminal information at this level of processing is unavailable. Here, in agreement with human functional imaging studies, we found that 26% of neurons in the mouse piriform cortex (PCX) display modulation in firing to carbon dioxide (CO2), an odorless stimulant with known trigeminal capacity. Interestingly, CO2 was represented within the PCX by distinct temporal dynamics, differing from those evoked by odor. Experiments with ascending concentrations of isopentyl acetate, an odorant known to elicit both olfactory and trigeminal sensations, resulted in morphing of the temporal dynamics of stimulus-evoked responses. Whereas low concentrations of odorant evoked responses upon stimulus onset, high concentrations of odorant and/or CO2 often evoked responses structured to stimulus offset. These physiological experiments in mice suggest that PCX neurons possess the capacity to encode for stimulus modality (olfactory vs trigeminal) by differential patterns of firing. These data provide mechanistic insights into the influences of trigeminal information on odor processing and place constraints on models of olfactory-trigeminal sensory integration.