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Nature Neuroscience Nov 2021The basolateral amygdala (BLA) plays essential roles in behaviors motivated by stimuli with either positive or negative valence, but how it processes motivationally...
The basolateral amygdala (BLA) plays essential roles in behaviors motivated by stimuli with either positive or negative valence, but how it processes motivationally opposing information and participates in establishing valence-specific behaviors remains unclear. Here, by targeting Fezf2-expressing neurons in the BLA, we identify and characterize two functionally distinct classes in behaving mice, the negative-valence neurons and positive-valence neurons, which innately represent aversive and rewarding stimuli, respectively, and through learning acquire predictive responses that are essential for punishment avoidance or reward seeking. Notably, these two classes of neurons receive inputs from separate sets of sensory and limbic areas, and convey punishment and reward information through projections to the nucleus accumbens and olfactory tubercle, respectively, to drive negative and positive reinforcement. Thus, valence-specific BLA neurons are wired with distinctive input-output structures, forming a circuit framework that supports the roles of the BLA in encoding, learning and executing valence-specific motivated behaviors.
Topics: Amygdala; Animals; Attention; Avoidance Learning; Corpus Striatum; DNA-Binding Proteins; Female; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Motivation; Nerve Net; Nerve Tissue Proteins
PubMed: 34663958
DOI: 10.1038/s41593-021-00927-0 -
The Journal of Neuroscience : the... Sep 2020In the mid-19th century, a misconception was born, which understandably persists in the minds of many neuroscientists today. The eminent scientist Albert von Kölliker... (Review)
Review
In the mid-19th century, a misconception was born, which understandably persists in the minds of many neuroscientists today. The eminent scientist Albert von Kölliker named a tubular-shaped piece of tissue found in the brains of all mammals studied to date, the tuberculum olfactorium - or what is commonly known as the olfactory tubercle (OT). In doing this, Kölliker ascribed "olfactory" functions and an "olfactory" purpose to the OT. The OT has since been classified as one of several olfactory cortices. However, further investigations of OT functions, especially over the last decade, have provided evidence for roles of the OT beyond olfaction, including in learning, motivated behaviors, and even seeking of psychoactive drugs. Indeed, research to date suggests caution in assigning the OT with a purely olfactory role. Here, I build on previous research to synthesize a model wherein the OT, which may be more appropriately termed the "tubular striatum" (TuS), is a neural system in which sensory information derived from an organism's experiences is integrated with information about its motivational states to guide affective and behavioral responses.
Topics: Animals; Corpus Striatum; Humans; Olfactory Perception
PubMed: 32968026
DOI: 10.1523/JNEUROSCI.1109-20.2020 -
Nature Communications Oct 2023The ventral striatum is a reward center implicated in the pathophysiology of depression. It contains islands of Calleja, clusters of dopamine D3 receptor-expressing...
The ventral striatum is a reward center implicated in the pathophysiology of depression. It contains islands of Calleja, clusters of dopamine D3 receptor-expressing granule cells, predominantly in the olfactory tubercle (OT). These OT D3 neurons regulate self-grooming, a repetitive behavior manifested in affective disorders. Here we show that chronic restraint stress (CRS) induces robust depression-like behaviors in mice and decreases excitability of OT D3 neurons. Ablation or inhibition of these neurons leads to depression-like behaviors, whereas their activation ameliorates CRS-induced depression-like behaviors. Moreover, activation of OT D3 neurons has a rewarding effect, which diminishes when grooming is blocked. Finally, we propose a model that explains how OT D3 neurons may influence dopamine release via synaptic connections with OT spiny projection neurons (SPNs) that project to midbrain dopamine neurons. Our study reveals a crucial role of OT D3 neurons in bidirectionally mediating depression-like behaviors, suggesting a potential therapeutic target.
Topics: Mice; Animals; Islands of Calleja; Depression; Ventral Striatum; Olfactory Tubercle; Dopaminergic Neurons
PubMed: 37898623
DOI: 10.1038/s41467-023-42662-z -
Frontiers in Neural Circuits 2024The olfactory tubercle (OT) is a unique part of the olfactory cortex of the mammal brain in that it is also a component of the ventral striatum. It is crucially involved... (Review)
Review
The olfactory tubercle (OT) is a unique part of the olfactory cortex of the mammal brain in that it is also a component of the ventral striatum. It is crucially involved in motivational behaviors, particularly in adaptive olfactory learning. This review introduces the basic properties of the OT, its synaptic connectivity with other brain areas, and the plasticity of the connectivity associated with learning behavior. The adaptive properties of olfactory behavior are discussed further based on the characteristics of OT neuronal circuits.
Topics: Animals; Neuronal Plasticity; Humans; Olfactory Tubercle; Learning
PubMed: 38841557
DOI: 10.3389/fncir.2024.1423505 -
Frontiers in Neural Circuits 2024Olfactory dysfunctions decrease daily quality of life (QOL) in part by reducing the pleasure of eating. Olfaction plays an essential role in flavor sensation and... (Review)
Review
Olfactory dysfunctions decrease daily quality of life (QOL) in part by reducing the pleasure of eating. Olfaction plays an essential role in flavor sensation and palatability. The decreased QOL due to olfactory dysfunction is speculated to result from abnormal neural activities in the olfactory and limbic areas of the brain, as well as peripheral odorant receptor dysfunctions. However, the specific underlying neurobiological mechanisms remain unclear. As the olfactory tubercle (OT) is one of the brain's regions with high expression of endogenous opioids, we hypothesize that the mechanism underlying the decrease in QOL due to olfactory dysfunction involves the reduction of neural activity in the OT and subsequent endogenous opioid release in specialized subregions. In this review, we provide an overview and recent updates on the OT, the endogenous opioid system, and the pleasure systems in the brain and then discuss our hypothesis. To facilitate the effective treatment of olfactory dysfunctions and decreased QOL, elucidation of the neurobiological mechanisms underlying the pleasure of eating through flavor sensation is crucial.
Topics: Humans; Quality of Life; Animals; Smell; Opioid Peptides; Olfactory Tubercle; Olfaction Disorders
PubMed: 38872907
DOI: 10.3389/fncir.2024.1408189 -
Neuropeptides Aug 2019Neurotensin (Nts) is a neuropeptide implicated in the regulation of many facets of physiology, including cardiovascular tone, pain processing, ingestive behaviors,...
Neurotensin (Nts) is a neuropeptide implicated in the regulation of many facets of physiology, including cardiovascular tone, pain processing, ingestive behaviors, locomotor drive, sleep, addiction and social behaviors. Yet, there is incomplete understanding about how the various populations of Nts neurons distributed throughout the brain mediate such physiology. This knowledge gap largely stemmed from the inability to simultaneously identify Nts cell bodies and manipulate them . One means of overcoming this obstacle is to study mice crossed onto a Cre-inducible green fluorescent reporter line ( mice), as these mice permit both visualization and modulation of specific populations of Nts neurons (using Cre-inducible viral and genetic tools) to reveal their function. Here we provide a comprehensive characterization of the distribution and relative densities of the Nts-GFP populations observed throughout the male mouse brain, which will pave the way for future work to define their physiologic roles. We also compared the distribution of Nts-GFP neurons with - Hybridization (-ISH) data from the adult mouse brain. By comparing these data sets we can distinguish Nts-GFP populations that may only transiently express Nts during development but not in the mature brain, and hence which populations may not be amenable to Cre-mediated manipulation in adult mice. This atlas of Nts-GFP neurons will facilitate future studies using the line to describe the physiological functions of individual Nts populations and how modulating them may be useful to treat disease.
Topics: Animals; Atlases as Topic; Brain; Male; Mice, Inbred C57BL; Mice, Transgenic; Neurons; Neurotensin
PubMed: 31079844
DOI: 10.1016/j.npep.2019.05.001 -
Nature Neuroscience Dec 2021The striatum comprises multiple subdivisions and neural circuits that differentially control motor output. The islands of Calleja (IC) contain clusters of densely packed...
The striatum comprises multiple subdivisions and neural circuits that differentially control motor output. The islands of Calleja (IC) contain clusters of densely packed granule cells situated in the ventral striatum, predominantly in the olfactory tubercle (OT). Characterized by expression of the D3 dopamine receptor, the IC are evolutionally conserved, but have undefined functions. Here, we show that optogenetic activation of OT D3 neurons robustly initiates self-grooming in mice while suppressing other ongoing behaviors. Conversely, optogenetic inhibition of these neurons halts ongoing grooming, and genetic ablation reduces spontaneous grooming. Furthermore, OT D3 neurons show increased activity before and during grooming and influence local striatal output via synaptic connections with neighboring OT neurons (primarily spiny projection neurons), whose firing rates display grooming-related modulation. Our study uncovers a new role of the ventral striatum's IC in regulating motor output and has important implications for the neural control of grooming.
Topics: Animals; Corpus Striatum; Grooming; Islands of Calleja; Mice; Neurons; Olfactory Tubercle; Ventral Striatum
PubMed: 34795450
DOI: 10.1038/s41593-021-00952-z -
Neuroscience Research May 2023The olfactory centres are the evolutionary oldest and most conservative area of the telencephalon. Olfactory deficiencies are involved in a large spectrum of neurologic... (Review)
Review
The olfactory centres are the evolutionary oldest and most conservative area of the telencephalon. Olfactory deficiencies are involved in a large spectrum of neurologic disorders and neurodegenerative diseases. The growing interest in human olfaction has been also been driven by COVID-19-induced transitional anosmia. Nevertheless, recent data on the human olfactory centres concerning normal histology and morphogenesis are rare. Published data in the field are mainly restricted to classic studies with non-uniform nomenclature and varied definitions of certain olfactory areas. While the olfactory system in model animals (rats, mice, and more rarely non-human primates) has been extensively investigated, the developmental timetable of olfactory centres in both human prenatal and postnatal ontogeny are poorly understood and unsystemised, which complicates the process of analysing human material, including medical researches. The main purpose of this review is to provide and discuss relevant morphological data on the normal ontogeny of the human olfactory centres, with a focus on the timetable of maturation and developmental cytoarchitecture, and with special reference to the definitions and terminology of certain olfactory areas.
Topics: Pregnancy; Female; Humans; Rats; Animals; Mice; Smell; COVID-19; Primates; Olfactory Bulb; Olfactory Pathways
PubMed: 36521642
DOI: 10.1016/j.neures.2022.12.005 -
The Journal of Neuroscience : the... Jun 2024The olfactory tubercle (TUB), also called the tubular striatum, receives direct input from the olfactory bulb and, along with the nucleus accumbens, is one of the two...
The olfactory tubercle (TUB), also called the tubular striatum, receives direct input from the olfactory bulb and, along with the nucleus accumbens, is one of the two principal components of the ventral striatum. As a key component of the reward system, the ventral striatum is involved in feeding behavior, but the vast majority of research on this structure has focused on the nucleus accumbens, leaving the TUB's role in feeding behavior understudied. Given the importance of olfaction in food seeking and consumption, olfactory input to the striatum should be an important contributor to motivated feeding behavior. Yet the TUB is vastly understudied in humans, with very little understanding of its structural organization and connectivity. In this study, we analyzed macrostructural variations between the TUB and the whole brain and explored the relationship between TUB structural pathways and feeding behavior, using body mass index (BMI) as a proxy in females and males. We identified a unique structural covariance between the TUB and the periaqueductal gray (PAG), which has recently been implicated in the suppression of feeding. We further show that the integrity of the white matter tract between the two regions is negatively correlated with BMI. Our findings highlight a potential role for the TUB-PAG pathway in the regulation of feeding behavior in humans.
Topics: Humans; Male; Female; Feeding Behavior; Adult; Periaqueductal Gray; Olfactory Tubercle; Magnetic Resonance Imaging; Young Adult; Neural Pathways
PubMed: 38755004
DOI: 10.1523/JNEUROSCI.2342-23.2024 -
Cerebral Cortex (New York, N.Y. : 1991) Feb 2023Sensory 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...
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.
Topics: Rats; Animals; Smell; Olfactory Bulb; Odorants; Brain; Prefrontal Cortex
PubMed: 35511680
DOI: 10.1093/cercor/bhac153