Testing effects of trigeminal stimulation on binary odor mixture quality in rats.

Prior attempts at forming theoretical predictions regarding the quality of binary odor mixtures have failed to find any consistent predictor for overshadowing of one component in a binary mixture by the other. We test here the hypothesis that trigeminality contributes to overshadowing effects in binary mixture perception. Most odorants stimulate the trigeminal nerve in the nasal sensory epithelium. In the current study we test rats' ability to detect component odorants in four binary odor sets chosen for their relative trigeminality. We predicted that the difference in trigeminal intensity would predict the degree of overshadowing by boosting or suppressing perceptual intensity of these odorants during learning or during mixture perception. We used a two-alternative choice (TAC) task in which rats were trained to recognize the two components of each mixture and tested on a range of mixtures of the two without reinforcement. We found that even though odorant concentrations were adjusted to balance volatility, all odor sets produced asymmetric psychometric curves. Odor pairs with the greatest difference in trigeminality showed overshadowing by the odorant with weaker trigeminal properties. Odor sets with more evenly matched trigeminal properties also showed asymmetry that was not predicted by either small differences in volatility or trigeminality. Thus, trigeminal properties may influence overshadowing in odor mixtures, but other factors are also likely involved. These mixed results further support the need to test each odor mixture to determine its odor quality and underscore recent results at the level of olfactory receptor neurons that show massive and unpredictable inhibition among odorants in complex mixtures.

Modified Wavelet Analyses Permit Quantification of Dynamic Interactions Between Ultradian and Circadian Rhythms.

Circadian rhythms provide daily temporal structure to cellular and organismal biological processes, ranging from gene expression to cognition. Higher-frequency (intradaily) ultradian rhythms are similarly ubiquitous but have garnered far less empirical study, in part because of the properties that define them-multimodal periods, non-stationarity, circadian harmonics, and diurnal modulation-pose challenges to their accurate and precise quantification. Wavelet analyses are ideally suited to address these challenges, but wavelet-based measurement of ultradian rhythms has remained largely idiographic. Here, we describe novel analytical approaches, based on discrete and continuous wavelet transforms, which permit quantification of rhythmic power distribution across a broad ultradian spectrum, as well as precise identification of period within empirically determined ultradian bands. Moreover, the aggregation of normalized wavelet matrices allows group-level analyses of experimental treatments, thereby circumventing limitations of idiographic approaches. The accuracy and precision of these wavelet analyses were validated using in silico and in vivo models with known ultradian features. Experiments in male and female mice yielded robust and repeatable measures of ultradian period and power in home cage locomotor activity, confirming and extending reports of ultradian rhythm modulation by sex, gonadal hormones, and circadian entrainment. Seasonal changes in day length modulated ultradian period and power, and exerted opposite effects in the light and dark phases of the 24 h day, underscoring the importance of evaluating ultradian rhythms with attention to circadian phase. Sex differences in ultradian rhythms were more prominent at night and depended on gonadal hormones in male mice. Thus, relatively straightforward modifications to the wavelet procedure allowed quantification of ultradian rhythms with appropriate time-frequency resolution, generating accurate, and repeatable measures of period and power which are suitable for group-level analyses. These analytical tools may afford deeper understanding of how ultradian rhythms are generated and respond to interoceptive and exteroceptive cues.

COVID-19 and olfactory dysfunction: a looming wave of dementia?

Olfactory dysfunction is a hallmark symptom of COVID-19 disease resulting from the SARS-CoV-2 virus. The cause of the sudden and usually temporary anosmia that most people suffer from COVID-19 is likely entirely peripheral-inflammation and other damage caused by the virus in the sensory epithelium inside the upper recesses of the nasal cavity can damage or prevent chemicals from properly activating the olfactory sensory neurons. However, persistent olfactory dysfunction from COVID-19, in the form of hyposmia and parosmia (decreased or altered smell) may affect as many as 15 million people worldwide. This epidemic of olfactory dysfunction is thus a continuing public health concern. Mounting evidence suggests that the SARS-CoV-2 virus itself or inflammation from the immune response in the nasal sensory epithelium may invade the olfactory bulb, likely via non-neuronal transmission. COVID-19-related long-term olfactory dysfunction and early damage to olfactory and limbic brain regions suggest a pattern of degeneration similar to that seen in early stages of Alzheimer's disease, Parkinson's disease, and Lewy body dementia. Thus, long-term olfactory dysfunction coupled with cognitive and emotional disturbance from COVID-19 may be the first signs of delayed onset dementia from neurodegeneration. Few treatments are known to be effective to prevent further degeneration, but the first line of defense against degeneration may be olfactory and environmental enrichment. There is a pressing need for more research on treatments for olfactory dysfunction and longitudinal studies including cognitive and olfactory function from patients who have recovered from even mild COVID-19.NEW & NOTEWORTHY More than 15 million people worldwide experience persistent COVID-19 olfactory dysfunction, possibly caused by olfactory bulb damage. SARS-CoV-2 can cause inflammation and viral invasion of the olfactory bulb, initiating a cascade of degeneration similar to Alzheimer's disease and Lewy body disease. People who have had even mild cases of COVID-19 show signs of degeneration in cortical areas connected with the olfactory system. These data suggest a wave of post-COVID dementia in the coming decades.

Long-Range Respiratory and Theta Oscillation Networks Depend on Spatial Sensory Context.

Neural oscillations can couple networks of brain regions, especially at lower frequencies. The nasal respiratory rhythm, which elicits robust olfactory bulb oscillations, has been linked to episodic memory, locomotion, and exploration, along with widespread oscillatory coherence. The piriform cortex is implicated in propagating the olfactory-bulb-driven respiratory rhythm, but this has not been tested explicitly in the context of both hippocampal theta and nasal respiratory rhythm during exploratory behaviors. We investigated systemwide interactions during foraging behavior, which engages respiratory and theta rhythms. Local field potentials from the olfactory bulb, piriform cortex, dentate gyrus, and CA1 of hippocampus, primary visual cortex, and nasal respiration were recorded simultaneously from male rats. We compared interactions among these areas while rats foraged using either visual or olfactory spatial cues. We found high coherence during foraging compared with home cage activity in two frequency bands that matched slow and fast respiratory rates. Piriform cortex and hippocampus maintained strong coupling at theta frequency during periods of slow respiration, whereas other pairs showed coupling only at the fast respiratory frequency. Directional analysis shows that the modality of spatial cues was matched to larger influences in the network by the respective primary sensory area. Respiratory and theta rhythms also coupled to faster oscillations in primary sensory and hippocampal areas. These data provide the first evidence of widespread interactions among nasal respiration, olfactory bulb, piriform cortex, and hippocampus in awake freely moving rats, and support the piriform cortex as an integrator of respiratory and theta activity.SIGNIFICANCE STATEMENT Recent studies have shown widespread interactions between the nasally driven respiratory rhythm and neural oscillations in hippocampus and neocortex. With this study, we address how the respiratory rhythm interacts with ongoing slow brain rhythms across olfactory, hippocampal, and visual systems in freely moving rats. Patterns of network connectivity change with behavioral state, with stronger interactions at fast and slow respiratory frequencies during foraging as compared with home cage activity. Routing of interactions between sensory cortices depends on the modality of spatial cues present during foraging. Functional connectivity and cross-frequency coupling analyses suggest strong bidirectional interactions between olfactory and hippocampal systems related to respiration and point to the piriform cortex as a key area for mediating respiratory and theta rhythms.

Odor identity can be extracted from the reciprocal connectivity between olfactory bulb and piriform cortex in humans.

Neuronal oscillations route external and internal information across brain regions. In the olfactory system, the two central nodes-the olfactory bulb (OB) and the piriform cortex (PC)-communicate with each other via neural oscillations to shape the olfactory percept. Communication between these nodes have been well characterized in non-human animals but less is known about their role in the human olfactory system. Using a recently developed and validated EEG-based method to extract signals from the OB and PC sources, we show in healthy human participants that there is a bottom-up information flow from the OB to the PC in the beta and gamma frequency bands, while top-down information from the PC to the OB is facilitated by delta and theta oscillations. Importantly, we demonstrate that there was enough information to decipher odor identity above chance from the low gamma in the OB-PC oscillatory circuit as early as 100 ms after odor onset. These data further our understanding of the critical role of bidirectional information flow in human sensory systems to produce perception. However, future studies are needed to determine what specific odor information is extracted and communicated in the information exchange.

Transfer of Odor Perception From the Retronasal to the Orthonasal Pathway.

Although orthonasal odorants are often associated with the external environment, retronasal odorants are accompanied by consummatory behaviors and indicate an internal state of an animal. Our study aimed to examine whether the same odorants may generate a consistent perceptual experience when 2 olfactory routes potentiate variations in concentration in the nasal cavity and orosensory activation. A customized lick spout with vacuum removing odorants around the animal's nares was used to render a pure retronasal exposure experience. We found that pre-exposing rats to odorants retronasally with positive or negative reinforcers (sweet or bitter) lead to a significant learning rate difference between high- and low-vapor-pressure odorants. This effect was not observed for novel odorants, suggesting that odorants may generate similar perceptual quality in a volatility-dependent manner.

The rhythm of memory: how breathing shapes memory function.

The mammalian olfactory bulb displays a prominent respiratory rhythm, which is linked to the sniff cycle and is driven by sensory input from olfactory receptors in the nasal sensory epithelium. In rats and mice, respiratory frequencies occupy the same band as the hippocampal θ-rhythm, which has been shown to be a key player in memory processes. Hippocampal and olfactory bulb rhythms were previously found to be uncorrelated except in specific odor-contingency learning circumstances. However, many recent electrophysiological studies in both rodents and humans reveal a surprising cycle-by-cycle influence of nasal respiration on neuronal activity throughout much of the cerebral cortex beyond the olfactory system, including the prefrontal cortex, hippocampus, and subcortical structures. In addition, respiratory phase has been shown to influence higher-frequency oscillations associated with cognitive functions, including attention and memory, such as the power of γ-rhythms and the timing of hippocampal sharp wave ripples. These new findings support respiration's role in cognitive function, which is supported by studies in human subjects, in which nasal respiration has been linked to memory processes. Here, we review recent reports from human and rodent experiments that link respiration to the modulation of memory function and the neurophysiological processes involved in memory in rodents and humans. We argue that respiratory influence on the neuronal activity of two key memory structures, the hippocampus and prefrontal cortex, provides a potential neuronal mechanism behind respiratory modulation of memory.

Pharmacological manipulation of the olfactory bulb modulates beta oscillations: testing model predictions.

The mammalian olfactory bulb (OB) generates gamma (40-100 Hz) and beta (15-30 Hz) local field potential (LFP) oscillations. Gamma oscillations arise at the peak of inhalation supported by dendrodendritic interactions between glutamatergic mitral cells (MCs) and GABAergic granule cells (GCs). Beta oscillations are induced by odorants in learning or odor sensitization paradigms, but their mechanism and function are still poorly understood. When centrifugal OB inputs are blocked, beta oscillations disappear, but gamma oscillations persist. Centrifugal inputs target primarily GABAergic interneurons in the GC layer (GCL) and regulate GC excitability, suggesting a causal link between beta oscillations and GC excitability. Our previous modeling work predicted that convergence of excitatory/inhibitory inputs onto MCs and centrifugal inputs onto GCs increase GC excitability sufficiently to produce beta oscillations primarily through voltage dependent calcium channel-mediated GABA release, independently of NMDA channels. We test some of the predictions of this model by examining the influence of NMDA and muscarinic acetylcholine (ACh) receptors, which affect GC excitability in different ways, on beta oscillations. A few minutes after intrabulbar infusion, scopolamine (muscarinic antagonist) suppressed odor-evoked beta in response to a strong stimulus but increased beta power in response to a weak stimulus, as predicted by our model. Pyriform cortex (PC) beta power was unchanged. Oxotremorine (muscarinic agonist) suppressed all oscillations, likely from overinhibition. APV, an NMDA receptor antagonist, suppressed gamma oscillations selectively (in OB and PC), lending support to the model's prediction that beta oscillations can be supported independently of NMDA receptors. NEW & NOTEWORTHY Olfactory bulb local field potential beta oscillations appear to be gated by GABAergic granule cell excitability. Reducing excitability with scopolamine reduces beta induced by strong odors but increases beta induced by weak odors. Beta oscillations rely on the same synapse as gamma oscillations but, unlike gamma, can persist in the absence of NMDA receptor activation. Pyriform cortex beta oscillations maintain power when olfactory bulb beta power is low, and the system maintains beta band coherence.

The Physiological Foresight in Freeman's Work: Predictions and Verifications.

Freeman's studies on the physiology of the mammalian olfactory system were based on his characterization of activity of neural masses, based on a sigmoid relationship at the mesoscopic scale between population spiking activity as a result of continuous inputs. His early development of computational models to describe oscillatory responses of neural masses allowed him to predict physiological and anatomical properties, some of which required decades of research to be confirmed. His models of neural masses therefore allow us to link between basic physiology and cognitive processes. Through the study of brain physiology at the mesoscopic level, we can understand how internally generated meaning-based responses to sensory input become action and how action leads to perception.

Task-Dependent Behavioral Dynamics Make the Case for Temporal Integration in Multiple Strategies during Odor Processing.

Differing results in olfactory-based decision-making research regarding the amount of time that rats and mice use to identify odors have led to some disagreements about odor-processing mechanics, including whether or not rodents use temporal integration (i.e., sniffing longer to identify odors better). Reported differences in behavioral strategies may be due to the different types of tasks used in different laboratories. Some researchers have reported that animals performing two-alternative choice (TAC) tasks need only 1-2 sniffs and do not increase performance with longer sampling. Others have reported that animals performing go/no-go (GNG) tasks increase sampling times and performance for difficult discriminations, arguing for temporal integration. We present results from four experiments comparing GNG and TAC tasks over several behavioral variables (e.g., performance, sampling duration). When rats know only one task, they perform better in GNG than in TAC. However, performance was not statistically different when rats learned and were tested in both tasks. Rats sample odors longer in GNG than in TAC, even when they know both tasks and perform them in the same or different sessions. Longer sampling is associated with better performance for both tasks in difficult discriminations, which supports the case for temporal integration over ≥2-6 sniffs in both tasks. These results illustrate that generalizations from a single task about behavioral or cognitive abilities (e.g., processing, perception) do not capture the full range of complexity and can significantly impact inferences about general abilities in sensory perception.SIGNIFICANCE STATEMENT Behavioral tasks and training and testing history affect measured outcomes in cognitive tests. Rats sample odors longer in a go/no-go (GNG) than in a two-alternative choice (TAC) task, performing better in GNG unless they know both tasks. Odor-sampling time is extended in both tasks when the odors to be discriminated are very similar. Rats may extend sampling time to integrate odor information up to ∼0.5 s (2-6 sniffs). Such factors as task, task parameters, and training history affect decision times and performance, making it important to use multiple tasks when making inferences about sensory or cognitive processing.

Gamma and Beta Oscillations Define a Sequence of Neurocognitive Modes Present in Odor Processing.

UNLABELLED: Olfactory system beta (15-35 Hz) and gamma (40-110 Hz) oscillations of the local field potential in mammals have both been linked to odor learning and discrimination. Gamma oscillations represent the activity of a local network within the olfactory bulb, and beta oscillations represent engagement of a systemwide network. Here, we test whether beta and gamma oscillations represent different cognitive modes using the different demands of go/no-go and two-alternative choice tasks that previously were suggested to favor beta or gamma oscillations, respectively. We reconcile previous studies and show that both beta and gamma oscillations occur in both tasks, with gamma dominating the early odor sampling period (2-4 sniffs) and beta dominating later. The relative power and coherence of both oscillations depend separately on multiple factors within both tasks without categorical differences across tasks. While the early/gamma-associated period occurs in all trials, rats can perform above chance without the later/beta-associated period. Longer sampling, which includes beta oscillations, is associated with better performance. Gamma followed by beta oscillations therefore represents a sequence of cognitive and neural states during odor discrimination, which can be separately modified depending on the demands of a task and odor discrimination. Additionally, fast (85 Hz) and slow (70 Hz) olfactory bulb gamma oscillation sub-bands have been hypothesized to represent tufted and mitral cell networks, respectively (Manabe and Mori, 2013). We find that fast gamma favors the early and slow gamma the later (beta-dominated) odor-sampling period and that the relative contributions of these oscillations are consistent across tasks. SIGNIFICANCE STATEMENT: Olfactory system gamma (40-110 Hz) and beta (15-35 Hz) oscillations of the local field potential indicate different neural firing statistics and functional circuits. We show that gamma and beta oscillations occur in stereotyped sequence during odor sampling in associative tasks, with local gamma dominating the first 250 ms of odor sniffing, followed by systemwide beta as behavioral responses are prepared. Oscillations and coupling strength between brain regions are modulated by task, odor, and learning, showing that task features can dramatically adjust the dynamics of a cortical sensory system, which changes state every ∼250 ms. Understanding cortical circuits, even at the biophysical level, depends on careful use of multiple behavioral contexts and stimuli.

Granule cell excitability regulates gamma and beta oscillations in a model of the olfactory bulb dendrodendritic microcircuit.

Odors evoke gamma (40-100 Hz) and beta (20-30 Hz) oscillations in the local field potential (LFP) of the mammalian olfactory bulb (OB). Gamma (and possibly beta) oscillations arise from interactions in the dendrodendritic microcircuit between excitatory mitral cells (MCs) and inhibitory granule cells (GCs). When cortical descending inputs to the OB are blocked, beta oscillations are extinguished whereas gamma oscillations become larger. Much of this centrifugal input targets inhibitory interneurons in the GC layer and regulates the excitability of GCs, which suggests a causal link between the emergence of beta oscillations and GC excitability. We investigate the effect that GC excitability has on network oscillations in a computational model of the MC-GC dendrodendritic network with Ca(2+)-dependent graded inhibition. Results from our model suggest that when GC excitability is low, the graded inhibitory current mediated by NMDA channels and voltage-dependent Ca(2+) channels (VDCCs) is also low, allowing MC populations to fire in the gamma frequency range. When GC excitability is increased, the activation of NMDA receptors and other VDCCs is also increased, allowing the slow decay time constants of these channels to sustain beta-frequency oscillations. Our model argues that Ca(2+) flow through VDCCs alone could sustain beta oscillations and that the switch between gamma and beta oscillations can be triggered by an increase in the excitability state of a subpopulation of GCs.

Analysis of coherent activity between retrosplenial cortex, hippocampus, thalamus, and anterior cingulate cortex during retrieval of recent and remote context fear memory.

Memory for contextual fear conditioning relies upon the retrosplenial cortex (RSC) regardless of how long ago conditioning occurred, whereas areas connected to the RSC, such as the dorsal hippocampus (DH) and anterior cingulate cortex (ACC) appear to play time-limited roles. To better understand whether these brain regions functionally interact during memory processing and how the passage of time affects these interactions, we simultaneously recorded local field potentials (LFPs) from these three regions as well as anterior dorsal thalamus (ADT), which provides one of the strongest inputs to RSC, and measured coherence of oscillatory activity within the theta (4-12Hz) and gamma (30-80Hz) frequency bands. We identified changes of theta coherence related to encoding, retrieval, and extinction of context fear, whereas changes in gamma coherence were restricted to fear extinction. Specifically, exposure to a novel context and retrieval of recently acquired fear conditioning memory were associated with increased theta coherence between RSC and all three other structures. In contrast, RSC-DH and RSC-ADT theta coherence were decreased in mice that successfully retrieved, relative to mice that failed to retrieve, remote memory. Greater RSC-ADT theta and gamma coherence were observed during recent, compared to remote, extinction of freezing responses. Thus, the degree of coherence between RSC and connected brain areas may predict and contribute to context memory retrieval and retrieval-related phenomena such as fear extinction. Importantly, although theta coherence in this circuit increases during memory encoding and retrieval of recent memory, failure to decrease RSC-DH theta coherence might be linked to retrieval deficit in the long term, and possibly contribute to aberrant memory processing characteristic of neuropsychiatric disorders.

Circadian Disruption Alters the Effects of Lipopolysaccharide Treatment on Circadian and Ultradian Locomotor Activity and Body Temperature Rhythms of Female Siberian Hamsters.

The effect of circadian rhythm (CR) disruption on immune function depends on the method by which CRs are disrupted. Behavioral and thermoregulatory responses induced by lipopolysaccharide (LPS) treatment were assessed in female Siberian hamsters in which circadian locomotor activity (LMA) rhythms were eliminated by exposure to a disruptive phase-shifting protocol (DPS) that sustains arrhythmicity even when hamsters are housed in a light-dark cycle. This noninvasive treatment avoids genome manipulations and neurological damage associated with other models of CR disruption. Circadian rhythmic (RHYTH) and arrhythmic (ARR) hamsters housed in a 16L:8D photocycle were injected with bacterial LPS near the onset of the light (zeitgeber time 1; ZT1) or dark (ZT16) phase. LPS injections at ZT16 and ZT1 elicited febrile responses in both RHYTH and ARR hamsters, but the effect was attenuated in the arrhythmic females. In ZT16, LPS inhibited LMA in the dark phase immediately after injection but not on subsequent nights in both chronotypes; in contrast, LPS at ZT1 elicited more enduring (~4 day) locomotor hypoactivity in ARR than in RHYTH hamsters. Power and period of dark-phase ultradian rhythms (URs) in LMA and Tb were markedly altered by LPS treatment, as was the power in the circadian waveform. Disrupted circadian rhythms in this model system attenuated responses to LPS in a trait- and ZT-specific manner; changes in UR period and power are novel components of the acute-phase response to infection that may affect energy conservation.

Olfactory system oscillations across phyla.

Neural oscillations are ubiquitous in olfactory systems of mammals, insects and molluscs. Neurophysiological and computational investigations point to common mechanisms for gamma or odor associated oscillations across phyla (40-100Hz in mammals, 20-30Hz in insects, 0.5-1.5Hz in molluscs), engaging the reciprocal dendrodendritic synapse between excitatory principle neurons and inhibitory interneurons in the olfactory bulb (OB), antennal lobe (AL), or procerebrum (PrC). Recent studies suggest important mechanisms that may modulate gamma oscillations, including neuromodulators and centrifugal input to the OB and AL. Beta (20Hz) and theta (2-12Hz) oscillations coordinate activity within and across brain regions. Olfactory beta oscillations are associated with odor learning and depend on centrifugal OB input, while theta oscillations are strongly associated with respiration.

The olfactory bulb theta rhythm follows all frequencies of diaphragmatic respiration in the freely behaving rat.

Sensory-motor relationships are part of the normal operation of sensory systems. Sensing occurs in the context of active sensor movement, which in turn influences sensory processing. We address such a process in the rat olfactory system. Through recordings of the diaphragm electromyogram (EMG), we monitored the motor output of the respiratory circuit involved in sniffing behavior, simultaneously with the local field potential (LFP) of the olfactory bulb (OB) in rats moving freely in a familiar environment, where they display a wide range of respiratory frequencies. We show that the OB LFP represents the sniff cycle with high reliability at every sniff frequency and can therefore be used to study the neural representation of motor drive in a sensory cortex.

Circuit oscillations in odor perception and memory.

Olfactory system neural oscillations as seen in the local field potential have been studied for many decades. Recent research has shown that there is a functional role for the most studied gamma oscillations (40-100Hz in rats and mice, and 20Hz in insects), without which fine odor discrimination is poor. When these oscillations are increased artificially, fine discrimination is increased, and when rats learn difficult and highly overlapping odor discriminations, gamma is increased in power. Because of the depth of study on this oscillation, it is possible to point to specific changes in neural firing patterns as represented by the increase in gamma oscillation amplitude. However, we know far less about the mechanisms governing beta oscillations (15-30Hz in rats and mice), which are best associated with associative learning of responses to odor stimuli. These oscillations engage every part of the olfactory system that has so far been tested, plus the hippocampus, and the beta oscillation frequency band is the one that is most reliably coherent with other regions during odor processing. Respiratory oscillations overlapping with the theta frequency band (2-12Hz) are associated with odor sniffing and normal breathing in rats. They also show coupling in some circumstances between olfactory areas and rare coupling between the hippocampus and olfactory bulb. The latter occur in specific learning conditions in which coherence strength is negatively or positively correlated with performance, depending on the task. There is still much to learn about the role of neural oscillations in learning and memory, but techniques that have been brought to bear on gamma oscillations (current source density, computational modeling, slice physiology, behavioral studies) should deliver much needed knowledge of these events.

Interplay between sniffing and odorant sorptive properties in the rat.

For decades it has been known that the olfactory sensory epithelium can act like a chromatograph, separating odorants based on their air-mucus sorptive properties (Mozell and Jagodowicz, 1973). It has been hypothesized that animals could take advantage of this property, modulating sniffing behavior to manipulate airflow and thereby directing odorant molecules to the portions of the olfactory epithelium where they are best detected (Schoenfeld and Cleland, 2005). We report here a test of this hypothesis in behaving rats, monitoring respiratory activity through diaphragm electromyogram, which allowed us to estimate nasal airflow. In our test rats had to detect either low-sorption (LS) or high-sorption (HS) monomolecular odorant targets from the same stimulus set of six binary odor mixtures. We found that it is more difficult for rats to detect LS than HS targets. Although sniffing bouts are the same duration for each group (∼500 ms), sniffing longer and using more inhalations results in better performance for rats assigned to detect LS targets. LS-detecting rats also increase the duration of individual inhalations (81 ms for LS- vs 69 ms for HS-detecting rats) and sniff at lower frequencies (7.8 Hz for LS- vs 8.6 Hz for HS-detecting rats) when learning to sense the target. When LS-detecting rats do discriminate well, they do so with lower airflow, more sniffs, and lower frequency of sniffing than HS-detecting counterparts. These data show that rats adjust sniff strategies as a function of odorant sorptiveness and provide support for the chromatographic and zonation hypotheses.