Leslie M. Kay

The hippocampus and neocortex are thought to undergo reorganization to incorporate new information during learning. How can we identify network states that indicate learning is occurring? In the hippocampus, one network signature with these properties is the sharp wave–ripple (SWR), which occurs more frequently during initial learning. However, it remains unclear which neural signatures track changes in neocortical networks during learning. We therefore recorded local field potentials simultaneously from the dorsal hippocampus (CA1) and prefrontal cortex (PFC) as male rats learned spatial navigation tasks. After animals reached goal locations, we found beta frequency (∼20 Hz) oscillations in PFC that increased in power with improvements in performance across days of training. In contrast, the rate and size of hippocampal SWRs decreased over the same period. Furthermore, goal-entry beta in PFC but not in CA1 was correlated with reward likelihood. Our results suggest that neocortical beta oscillations develop gradually as learning occurs, which stands in contrast to the reduction in hippocampal SWRs as the task becomes familiar. We hypothesize that PFC beta oscillations and hippocampal SWRs are complementary markers of experience-dependent change in hippocampal–neocortical networks during learning.

Olfactory perception relies on active sampling, with successive inhalations providing discrete sensory inputs that in humans can be separated by several seconds. Yet odors are perceived as continuous and stable, raising the question of how the brain integrates sensory information across these temporal gaps. Here, we used electrobulbogram (EBG) recordings in 48 participants to demonstrate that successive sniffs are not processed independently but are linked through recurrent oscillatory dynamics between the olfactory bulb (OB) and piriform cortex (PC). Specifically, first-sniff alpha/beta activity in the OB and OB–PC functional connectivity predicted second-sniff gamma power, while transfer entropy indicated a directional temporal dependence from first-sniff alpha/beta to second-sniff gamma dynamics. In parallel, second-sniff gamma activity selectively tracked subjective odor valence prior to inhalation onset. At the network level, the PC exhibited stronger alpha/beta-band connectivity with orbitofrontal, insular, and prefrontal regions during the first sniff than during the second, suggesting that early evaluative processing provides a contextual signal that is carried forward to shape subsequent sensory representations. These results demonstrate that the human OB-PC circuit carries evaluative information across inhalations through directed alpha/beta-to-gamma interactions, providing a mechanism for maintaining perceptual continuity in a sensory system defined by temporally discrete sampling.

When sampling odors, humans typically take a single long sniff, unlike most other mammals who sample odors through bouts of rapid repetitive sniffing. Decades of work has established that rapid sniffing rhythms underlie the organizational principles of odor coding, with sniff speed clocking odor responses in the olfactory bulb. In the absence of rapid sniffing, how are odor responses organized in the human olfactory system? Because most mammals sniff at rates centered around the theta frequency, we hypothesized that the olfactory bulb exploits a theta-range neural oscillation to set the pace of odor coding in the system. Here, we used high-precision neural recordings from the human olfactory bulb to show that initiation of a sniff elicits and temporally aligns theta oscillations in the bulb and that sniff-induced theta oscillations organize the timing and amplitude of odor responses. These findings suggest that, despite the lack of rapid sniffing bouts in humans, the system has preserved a similarly timed unit of olfactory processing.

Olfaction plays a large role in evolutionary processes. However, we know little about sex differences in olfactory bulb neurophysiology, and many scientists believe that females are more variable because of estrus. We show that female rats sniff odors for shorter durations than males and have lower power in neural oscillations related to cognition. Estrus was not related to variance in any measures. Finally, males and females show equal variance on these behavioral and physiological processes.

In many species, olfactory abilities in females are more sensitive than those in males. Studies in humans show that women have lower olfactory thresholds and are better able to discriminate and identify odors than men. In mice, odorants elicit faster activation from a larger number of olfactory sensory neurons in females than males. Our study explores sex differences in olfaction in Long Evans rats from a behavioral and electrophysiological perspective. Local field potentials (LFPs) in the olfactory bulb (OB) represent the coordinated activity of bulbar neurons. Olfactory gamma (65-120 Hz) and beta (15-30 Hz) oscillations have been functionally linked to odor perception. Spontaneous and odor-evoked OB LFPs were recorded from awake rats at the same time for 12 days. Odors used included urine of both sexes and monomolecular odorants characterized previously for correlation of volatility with behavior and OB oscillations. Sampling duration, baseline gamma and beta power, and odor-elicited beta and gamma power were analyzed. We find that females sample odorants for a shorter duration than males (close to 1s difference). While baseline gamma and beta power do not show significant differences between the two sexes, odor-elicited gamma and beta power in females is significantly lower than in males. Neither sampling duration nor beta and gamma power in females varied systematically with day of estrus. We further verify that variance of these behavioral and physiological measures is not different across sexes, adding to growing evidence that researchers need not be concerned about often- claimed additional variance in female subjects. New and Noteworthy: Olfaction plays a large role in evolutionary processes. However, we know little about sex differences in olfactory bulb neurophysiology, and many scientists believe that females are more variable due to estrus. We show that female rats sniff odors for shorter durations than males and have lower power in neural oscillations related to cognition. Estrus was not related to variance in any measures. Finally, males and females show equal variance on these behavioral and physiological processes.

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.

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.

This paper tests the hypothesis that the olfactory bulbectomy (OBx) model of major depressive disorder (MDD) is caused by a lack of OB gamma band oscillatory input to the limbic system. OBx is a catastrophic surgery accompanied by significant blood l...

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 STATEMENTRecent 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.