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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 -
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 -
The International Journal of... Apr 2024The understanding of the pathophysiology of schizophrenia as well as the mechanisms of action of antipsychotic drugs remains a challenge for psychiatry. The... (Review)
Review
The understanding of the pathophysiology of schizophrenia as well as the mechanisms of action of antipsychotic drugs remains a challenge for psychiatry. The demonstration of the therapeutic efficacy of several new atypical drugs targeting multiple different receptors, apart from the classical dopamine D2 receptor as initially postulated unique antipsychotic target, complicated even more conceptualization efforts. Here we discuss results suggesting a main role of the islands of Calleja, still poorly studied GABAergic granule cell clusters in the ventral striatum, as cellular targets of several innovative atypical antipsychotics (clozapine, cariprazine, and xanomeline/emraclidine) effective in treating also negative symptoms of schizophrenia. We will emphasize the potential role of dopamine D3 and M4 muscarinic acetylcholine receptor expressed at the highest level by the islands of Calleja, as well as their involvement in schizophrenia-associated neurocircuitries. Finally, we will discuss the implications of new data showing ongoing adult neurogenesis of the islands of Calleja as a very promising antipsychotic target linking long-life neurodevelopment and dopaminergic dysfunction in the striatum.
Topics: Antipsychotic Agents; Humans; Animals; Schizophrenia; Islands of Calleja; Neurogenesis
PubMed: 38629703
DOI: 10.1093/ijnp/pyae018 -
Scientific Reports Mar 2024The pathophysiology underlying the post-acute sequelae of COVID-19 remains understudied and poorly understood, particularly in healthy adults with a history of mild...
The pathophysiology underlying the post-acute sequelae of COVID-19 remains understudied and poorly understood, particularly in healthy adults with a history of mild infection. Chronic neuroinflammation may underlie these enduring symptoms, but studying neuroinflammatory phenomena in vivo is challenging, especially without a comparable pre-COVID-19 dataset. In this study, we present a unique dataset of 10 otherwise healthy individuals scanned before and after experiencing mild COVID-19. Two emerging MR-based methods were used to map pre- to post-COVID-19 brain temperature and free water changes. Post-COVID-19 brain temperature and free water increases, which are indirect biomarkers of neuroinflammation, were found in structures functionally associated with olfactory, cognitive, and memory processing. The largest pre- to post-COVID brain temperature increase was observed in the left olfactory tubercle (p = 0.007, 95% CI [0.48, 3.01]), with a mean increase of 1.75 °C. Notably, the olfactory tubercle is also the region of the primary olfactory cortex where participants with chronic olfactory dysfunction showed the most pronounced increases as compared to those without lingering olfactory dysfunction (adjusted p = 0.0189, 95% CI [1.42, 5.27]). These preliminary insights suggest a potential link between neuroinflammation and chronic cognitive and olfactory dysfunction following mild COVID-19, although further investigations are needed to improve our understanding of what underlies these phenomena.
Topics: Adult; Humans; Neuroinflammatory Diseases; Temperature; COVID-19; Brain; Olfaction Disorders; Water
PubMed: 38548815
DOI: 10.1038/s41598-024-57561-6 -
Neurobiology of Aging May 2024Hedonic perception deeply changes with aging, significantly impacting health and quality of life in elderly. In young adult mice, an odor hedonic signature is...
Hedonic perception deeply changes with aging, significantly impacting health and quality of life in elderly. In young adult mice, an odor hedonic signature is represented along the antero-posterior axis of olfactory bulb, and transferred to the olfactory tubercle and ventral tegmental area, promoting approach behavior. Here, we show that while the perception of unattractive odorants was unchanged in older mice (22 months), the appreciation of some but not all attractive odorants declined. Neural activity in the olfactory bulb and tubercle of older mice was consistently altered when attraction to pleasant odorants was impaired while maintained when the odorants kept their attractivity. Finally, in a self-stimulation paradigm, optogenetic stimulation of the olfactory bulb remained rewarding in older mice even without ventral tegmental area's response to the stimulation. Aging degrades behavioral and neural responses to some pleasant odorants but rewarding properties of olfactory bulb stimulation persisted, providing new insights into developing novel olfactory training strategies to elicit motivation even when the dopaminergic system is altered as observed in normal and/or neurodegenerative aging.
Topics: Humans; Mice; Animals; Aged; Odorants; Smell; Olfactory Perception; Quality of Life; Olfactory Bulb
PubMed: 38394723
DOI: 10.1016/j.neurobiolaging.2024.02.003 -
Brain and Behavior Dec 2023Since 2002, when we published our article about the anterior perforated substance (APS), the knowledge about the region has grown enormously.
INTRODUCTION
Since 2002, when we published our article about the anterior perforated substance (APS), the knowledge about the region has grown enormously.
OBJECTIVE
To make a better description of the anatomy of the zone with new dissection material added to the previous, to sustain the anatomical analysis of the MRI employing the SPACE sequence, interacting with our imagenology colleagues. Especially, we aim to identify and topographically localize by MRI the principal structures in APS-substantia innominata (SI).
METHOD
The presentation follows various steps: (1) location and boundaries of the zone and its neighboring areas; (2) schematic description of the region with simple outlines; (3) cursory revision of the SI and its three systems; (4) serial images of the dissections of the zone and its vessels, illustrated and completed when possible, by MRI images of a voluntary experimental subject (ES).
RESULTS
With this method, we could expose most of the structures of the region anatomically and imagenologically.
DISCUSSION
The zone can be approached for dissection with magnification and the habitual microsurgical instruments with satisfactory results. We think that fibers in this region should be followed by other anatomical methods in addition to tractography. The principal structures of ventral striopallidum and extended amygdala (EA) can be identified with the SPACE sequence. The amygdala and the basal ganglion of Meynert (BGM) are easily confused because of their similar signal. Anatomical clues can orient the clinician about the different clusters of the BGM in MRI.
CONCLUSIONS
The dissection requires a previous knowledge of the zone and a good amount of patience. The APS is a little space where concentrate essential vessels for the telencephalon, "en passage" or perforating, and neural structures of relevant functional import. From anatomical and MRI points of view, both neural and vascular structures follow a harmonious and topographically describable plan. The SPACE MRI sequence has proved to be a useful tool for identifying different structures in this area as the striatopallidal and EA. Anatomical knowledge of the fibers helps in the search of clusters of the basal ganglion.
Topics: Basal Ganglia; Substantia Innominata; Amygdala; Olfactory Tubercle; Basal Nucleus of Meynert
PubMed: 38010896
DOI: 10.1002/brb3.3029 -
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 Neuroscience 2023The olfactory tubercle (OT), which is a component of the olfactory cortex and ventral striatum, has functional domains that play a role in odor-guided motivated...
The olfactory tubercle (OT), which is a component of the olfactory cortex and ventral striatum, has functional domains that play a role in odor-guided motivated behaviors. Learning odor-guided attractive and aversive behavior activates the anteromedial (am) and lateral (l) domains of the OT, respectively. However, the mechanism driving learning-dependent activation of specific OT domains remains unknown. We hypothesized that the neuronal connectivity of OT domains is plastically altered through olfactory experience. To examine the plastic potential of synaptic connections to OT domains, we optogenetically stimulated intracortical inputs from the piriform cortex or sensory inputs from the olfactory bulb to the OT in mice in association with a food reward for attractive learning and electrical foot shock for aversive learning. For both intracortical and sensory connections, axon boutons that terminated in the OT domains were larger in the amOT than in the lOT for mice exhibiting attractive learning and larger in the lOT than in the amOT for mice exhibiting aversive learning. These results indicate that both intracortical and sensory connections to the OT domains have learning-dependent plastic potential, suggesting that this plasticity underlies learning-dependent activation of specific OT domains and the acquisition of appropriate motivated behaviors.
PubMed: 37680965
DOI: 10.3389/fnins.2023.1247375 -
Addiction Neuroscience Dec 2023Epidermal/brain fatty acid-binding protein 5 (FABP5) plays an integral role in the intracellular trafficking of bioactive lipids/endocannabinoids and the subsequent...
Epidermal/brain fatty acid-binding protein 5 (FABP5) plays an integral role in the intracellular trafficking of bioactive lipids/endocannabinoids and the subsequent initiation of cellular cascades affecting cannabinoid and dopamine (DA) systems. Social isolation (SI) and environmental enrichment (EE) during adolescence have been shown to impact DA signaling, and, specifically, DA transporter (DAT) and receptor levels of DA type 1 (D1) and 2 (D2); however, the relationship between FABP5, environment and DA signaling remains unclear. The present study quantified DAT and DA receptor levels in male/female FABP5-/- and FABP5+/+ mice raised in either SI or EE. Results showed that FABP5-/- mice had 6.09-8.81% greater D1 levels in striatal sub-regions of the caudal brain, independent of sex or environment. D1 levels were 8.03% greater only in the olfactory tubercle of enrichment-reared animals. In summary, these results supported that FABP5 plays an important function in regulating striatal DA signaling, and this may have important implications as a target with therapeutic potential for various psychiatric disorders.
PubMed: 37664218
DOI: 10.1016/j.addicn.2023.100118 -
BioRxiv : the Preprint Server For... Dec 2023The ways in which sensory stimuli acquire motivational valence through association with other stimuli is one of the simplest forms of learning. Though we have identified...
The ways in which sensory stimuli acquire motivational valence through association with other stimuli is one of the simplest forms of learning. Though we have identified many brain nuclei that play various roles in reward processing, a significant gap remains in understanding how valence encoding transforms through the layers of sensory processing. To address this gap, we carried out a comparative investigation of the olfactory tubercle (OT), and the ventral pallidum (VP) - 2 connected nuclei of the basal ganglia which have both been implicated in reward processing. First, using anterograde and retrograde tracing, we show that both D1 and D2 neurons of the OT project primarily to the VP and minimally elsewhere. Using 2-photon calcium imaging, we then investigated how the identity of the odor and reward contingency of the odor are differently encoded by neurons in either structure during a classical conditioning paradigm. We find that VP neurons robustly encode reward contingency, but not identity, in low-dimensional space. In contrast, OT neurons primarily encode odor identity in high-dimensional space. Though D1 OT neurons showed larger response vectors to rewarded odors than other odors, we propose this is better interpreted as identity encoding with enhanced contrast rather than as valence encoding. Finally, using a novel conditioning paradigm that decouples reward contingency and licking vigor, we show that both features are encoded by non-overlapping VP neurons. These results provide a novel framework for the striatopallidal circuit in which a high-dimensional encoding of stimulus identity is collapsed onto a low-dimensional encoding of motivational valence.
PubMed: 37577586
DOI: 10.1101/2023.08.01.551547