Faculty Bibliography

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.

We rapidly classify odors as pleasant or aversive, but the brain circuits underlying how odors motivate approach and avoidance responses are largely unknown. New research describes a direct path from the olfactory bulb to ventral striatum driving odor-mediated reward.

Developmental exposure to ethanol has a wide range of anatomical, cellular, physiological and behavioral impacts that can last throughout life. In humans, this cluster of effects is termed fetal alcohol spectrum disorder and is highly prevalent in western cultures. The ultimate expression of the effects of developmental ethanol exposure however can be influenced by post-exposure experience. Here we examined the effects of developmental binge exposure to ethanol (postnatal day 7) in C57BL/6By mice on a specific cohort of inter-related long-term outcomes including contextual memory, hippocampal parvalbumin-expressing neuron density, frontal cortex oscillations related to sleep-wake cycling including delta oscillation amplitude and sleep spindle density, and home-cage behavioral activity. When assessed in adults that were raised in standard housing, all of these factors were altered by early ethanol exposure compared to saline controls except home-cage activity. However, exposure to an enriched environment and exercise from weaning to postnatal day 90 reversed most of these ethanol-induced impairments including memory, CA1 but not dentate gyrus PV+ cell density, delta oscillations and sleep spindles, and enhanced home-cage behavioral activity in Saline- but not EtOH-treated mice. The results are discussed in terms of the inter-dependence of diverse developmental ethanol outcomes and potential mechanisms of post-exposure experiences to regulate those outcomes.

The roots of psychopathology frequently take shape during infancy in the context of parent-infant interactions and adversity. Yet, neurobiological mechanisms linking these processes during infancy remain elusive. Here, using responses to attachment figures among infants who experienced adversity as a benchmark, we assessed rat pup cortical local field potentials (LFPs) and behaviors exposed to adversity in response to maternal rough and nurturing handling by examining its impact on pup separation-reunion with the mother. We show that during adversity, pup cortical LFP dynamic range decreased during nurturing maternal behaviors, but was minimally impacted by rough handling. During reunion, adversity-experiencing pups showed aberrant interactions with mother and blunted cortical LFP. Blocking pup stress hormone during either adversity or reunion restored typical behavior, LFP power, and cross-frequency coupling. This translational approach suggests adversity-rearing produces a stress-induced aberrant neurobehavioral processing of the mother, which can be used as an early biomarker of later-life pathology.

Current non-invasive neuroimaging methods can assess neural activity in all areas of the human brain but the olfactory bulb (OB). The OB has been suggested to fulfill a role comparable to that of V1 and the thalamus in the visual system and have been closely linked to a wide range of olfactory tasks and neuropathologies. Here we present a method for non-invasive recording of signals from the human OB with millisecond precision. We demonstrate that signals obtained via recordings from EEG electrodes at the nasal bridge represent responses from the human olfactory bulb - recordings we term Electrobulbogram (EBG). The EBG will aid future olfactory-related translational work but can also potentially be implemented as an everyday clinical tool to detect pathology-related changes in human central olfactory processing in neurodegenerative diseases. In conclusion, the EBG is localized to the OB, is reliable, and follows response patterns demonstrated in non-human animal models.

Olfactory identification impairment might indicate future cognitive decline in elderly individuals. An unresolved question is to what extent this effect is dependent on the ApoE-ε4, a genotype associated with risk of Alzheimer's Disease (AD). Given the current concern about reproducibility in empirical research, we assessed this issue in a large sample (n = 1637) of older adults (60 - 96 years) from the population-based longitudinal Swedish National Study on Aging and Care in Kungsholmen (SNAC-K). A hierarchical regression analysis was carried out to determine if a low score on an odor identification test, and the presence of ApoE-ε4, would predict the magnitude of a prospective 6-year change in the Mini-Mental State Examination (MMSE) after controlling for demographic, health-related, and cognitive variables. We found that overall, lower odor identification performance was predictive of cognitive decline, and, as hypothesized, we found that the effect was most pronounced among ApoE-ε4 carriers. Our results from this high-powered sample suggest that in elderly carriers of the ApoE-ε4 allele, odor identification impairment provides an indication of future cognitive decline, which has relevance for the prognosis of AD.

The affective state is the combination of emotion and mood, with mood reflecting a running average of sequential emotional events together with an underlying internal affective state. There is now extensive evidence that odors can overtly or subliminally modulate mood and emotion. Relying primarily on neurobiological literature, here we review what is known about how odors can affect emotions/moods and how emotions/moods may affect odor perception. We take the approach that form can provide insight into function by reviewing major brain regions and neural circuits underlying emotion and mood, and then reviewing the olfactory pathway in the context of that emotion/mood network. We highlight the extensive neuroanatomical opportunities for odor-emotion/mood convergence, as well as functional data demonstrating reciprocal interactions between these processes. Finally, we explore how the odor- emotion/mood interplay is, or could be, used in medical and/or commercial applications.

Most odors are not composed of a single volatile chemical species, but rather are mixtures of many different volatile molecules, the perception of which is dependent on the identity and relative concentrations of the components. Changing either the identity or ratio of components can lead to shifts between configural and elemental perception of the mixture. For example, a 30/70 ratio of ethyl isobutyrate (odorant A, a strawberry scent) and ethyl maltol (odorant B, a caramel scent) is perceived as pineapple by humans - a configural percept distinct from the components. In contrast, a 68/32 ratio of the same odorants is perceived elementally, and is identified as the component odors. Here, we examined single-unit responses in the anterior and posterior piriform cortex (aPCX and pPCX) of mice to these A and B mixtures. We first demonstrate that mouse behavior is consistent with a configural/elemental perceptual shift as concentration ratio varies. We then compared responses to the configural mixture to those evoked by the elemental mixture, as well as to the individual components. Hierarchical cluster analyses suggest that in the mouse aPCX, the configural mixture was coded as distinct from both components, while the elemental mixture was coded as similar to the components. In contrast, mixture perception did not predict pPCX ensemble coding. Similar electrophysiological results were also observed in rats. The results suggest similar perceptual characteristics of the AB mixture across species, and a division in the roles of aPCX and pPCX in the coding of configural and elemental odor mixtures.

Sleep quality varies widely across individuals, especially during normal aging, with impaired sleep contributing to deficits in cognition and emotional regulation. Sleep can also be impacted by a variety of adverse events, including childhood adversity. Here we examined how early life adverse events impacted later life sleep structure and physiology using an animal model to test the relationship between early life adversity and sleep quality across the life span. Rat pups were exposed to an Adversity-Scarcity model from postnatal day 8-12, where insufficient bedding for nest building induces maternal maltreatment of pups. Polysomnography and sleep physiology were assessed in weaning, early adult and older adults. Early life adversity induced age-dependent disruptions in sleep and behavior, including lifelong spindle decreases and later life NREM sleep fragmentation. Given the importance of sleep in cognitive and emotional functions, these results highlight an important factor driving variation in sleep, cognition and emotion throughout the lifespan that suggest age-appropriate and trauma informed treatment of sleep problems.

Infant maltreatment increases vulnerability to physical and mental disorders, yet specific mechanisms embedded within this complex infant experience that induce this vulnerability remain elusive. To define critical features of maltreatment-induced vulnerability, rat pups were reared from postnatal day 8 (PN8) with a maltreating mother, which produced amygdala and hippocampal deficits and decreased social behavior at PN13. Next, we deconstructed the maltreatment experience to reveal sufficient and necessary conditions to induce this phenotype. Social behavior and amygdala deficits (volume, neurogenesis, c-Fos, local field potential) required combined chronic high corticosterone and maternal presence (not maternal behavior). Hippocampal deficits were induced by chronic high corticosterone regardless of social context. Causation was shown by blocking corticosterone during maltreatment and suppressing amygdala activity during social behavior testing. These results highlight (1) that early life maltreatment initiates multiple pathways to pathology, each with distinct causal mechanisms and outcomes, and (2) the importance of social presence on brain development.