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Obesity (Silver Spring, Md.) Aug 2020The current study examined whether adolescents with weight status ranging from lean to obesity showed weight-related differences in the default mode network (DMN), the...
OBJECTIVE
The current study examined whether adolescents with weight status ranging from lean to obesity showed weight-related differences in the default mode network (DMN), the executive function network (EFN), and the salience network (SN).
METHODS
One hundred sixty-four adolescents participated in a resting-state functional connectivity scan. A general linear model was used to examine differences in scan patterns among adolescents with lean weight, overweight, and obesity.
RESULTS
Adolescents with obesity compared with those with lean weight showed stronger within-SN connectivity among the medial orbitofrontal cortex, olfactory tubercle, and pallidum; however, they showed lower connectivity between the amygdala and SN regions (nucleus accumbens, thalamus, putamen). Those with obesity also showed lower connectivity between SN (amygdala, caudate) and DMN (parahippocampus, hippocampus, precuneus) regions. Adolescents with obesity compared with those with lean weight showed lower connectivity between SN (medial orbitofrontal cortex) and EFN (ventrolateral prefrontal cortex) regions.
CONCLUSIONS
Obesity appears to be related to stronger connectivity within and between regions implicated in determining the salience of stimuli, which may have implications for reward processing. Lower connectivity between SN and EFN regions may suggest that executive-control efforts are going "off-line" when salience and reward-processing regions are engaged in adolescents who have obesity.
Topics: Adolescent; Adult; Brain; Child, Preschool; Executive Function; Female; Humans; Magnetic Resonance Imaging; Male; Neural Pathways; Young Adult
PubMed: 32633100
DOI: 10.1002/oby.22853 -
Frontiers in Neurology 2020Autoimmune encephalitic syndromes include mutism, somnolence, movement disorder, and behavioral, or psychiatric symptoms. When paired with bilateral basal ganglia...
Autoimmune encephalitic syndromes include mutism, somnolence, movement disorder, and behavioral, or psychiatric symptoms. When paired with bilateral basal ganglia lesions on magnetic resonance imaging, these support the diagnosis of basal ganglia encephalitis (BGE). BGE is a rare but distinct entity of putative autoimmune etiology, with specific basal ganglia inflammation and acute movement disorders. A previous study identified dopamine-2 receptors (D2R) antibody to be positive in most BGE children, indicating that the D2R antibody may trigger the downstream pathological process in BGE patients. The highest levels of D2R are found in the striatum, the nucleus accumbens, and the olfactory tubercle. D2R antibody-positive BGE is widely reported in children. Here we present a 17-year-old girl with a typical clinical feature of basal ganglia encephalitis, who benefited from immune therapy.
PubMed: 32612568
DOI: 10.3389/fneur.2020.00471 -
Frontiers in Neuroanatomy 2020Gestational exposure to valproic acid (VPA) is known to cause behavioral deficits of sociability, matching similar alterations in human autism spectrum disorder (ASD)....
Gestational Exposure to Sodium Valproate Disrupts Fasciculation of the Mesotelencephalic Dopaminergic Tract, With a Selective Reduction of Dopaminergic Output From the Ventral Tegmental Area.
Gestational exposure to valproic acid (VPA) is known to cause behavioral deficits of sociability, matching similar alterations in human autism spectrum disorder (ASD). Available data are scarce on the neuromorphological changes in VPA-exposed animals. Here, we focused on alterations of the dopaminergic system, which is implicated in motivation and reward, with relevance to social cohesion. Whole brains from 7-day-old mice born to mothers given a single injection of VPA (400 mg/kg b.wt.) on E13.5 were immunostained against tyrosine hydroxylase (TH). They were scanned using the iDISCO method with a laser light-sheet microscope, and the reconstructed images were analyzed in 3D for quantitative morphometry. A marked reduction of mesotelencephalic (MT) axonal fascicles together with a widening of the MT tract were observed in VPA treated mice, while other major brain tracts appeared anatomically intact. We also found a reduction in the abundance of dopaminergic ventral tegmental (VTA) neurons, accompanied by diminished tissue level of DA in ventrobasal telencephalic regions (including the nucleus accumbens (NAc), olfactory tubercle, BST, substantia innominata). Such a reduction of DA was not observed in the non-limbic caudate-putamen. Conversely, the abundance of TH+ cells in the substantia nigra (SN) was increased, presumably due to a compensatory mechanism or to an altered distribution of TH+ neurons occupying the SN and the VTA. The findings suggest that defasciculation of the MT tract and neuronal loss in VTA, followed by diminished dopaminergic input to the ventrobasal telencephalon at a critical time point of embryonic development (E13-E14) may hinder the patterning of certain brain centers underlying decision making and sociability.
PubMed: 32581730
DOI: 10.3389/fnana.2020.00029 -
The Journal of Neuroscience : the... May 2020Rodents can successfully learn multiple novel stimulus-response associations after only a few repetitions when the contingencies predict reward. The circuits modified...
Rodents can successfully learn multiple novel stimulus-response associations after only a few repetitions when the contingencies predict reward. The circuits modified during such reinforcement learning to support decision-making are not known, but the olfactory tubercle (OT) and posterior piriform cortex (pPC) are candidates for decoding reward category from olfactory sensory input and relaying this information to cognitive and motor areas. Through single-cell recordings in behaving male and female C57BL/6 mice, we show here that an explicit representation for reward category emerges in the OT within minutes of learning a novel odor-reward association, whereas the pPC lacks an explicit representation even after weeks of overtraining. The explicit reward category representation in OT is visible in the first sniff (50-100 ms) of an odor on each trial, and precedes the motor action. Together, these results suggest that the coding of stimulus information required for reward prediction does not occur within olfactory cortex, but rather in circuits involving the olfactory striatum. Rodents are olfactory specialists and can use odors to learn contingencies quickly and well. We have found that mice can readily learn to place multiple odors into rewarded and unrewarded categories. Once they have learned the rule, they can do such categorization in a matter of minutes (<10 trials). We found that neural activity in olfactory cortex largely reflects sensory coding, with very little explicit information about categories. By contrast, neural activity in a brain region in the ventral striatum is rapidly modified in a matter of minutes to reflect reward category. Our experiments set up a paradigm for studying rapid sensorimotor reinforcement in a circuit that is right at the interface of sensory input and reward areas.
Topics: Animals; Female; Male; Mice; Mice, Inbred C57BL; Neurons; Olfactory Perception; Olfactory Tubercle; Piriform Cortex; Reward
PubMed: 32321744
DOI: 10.1523/JNEUROSCI.2604-19.2020 -
FEBS Open Bio May 2020Odor adaptation allows the olfactory system to regulate sensitivity to different stimulus intensities, which is essential for preventing saturation of the...
Odor adaptation allows the olfactory system to regulate sensitivity to different stimulus intensities, which is essential for preventing saturation of the cell-transducing machinery and maintaining high sensitivity to persistent and repetitive odor stimuli. Although many studies have investigated the structure and mechanisms of the mammalian olfactory system that responds to chemical sensation, few studies have considered differences in neuronal activation that depend on the manner in which the olfactory system is exposed to odorants, or examined activity patterns of olfactory-related regions in the brain under different odor exposure conditions. To address these questions, we designed three different odor exposure conditions that mimicked diverse odor environments and analyzed c-Fos-expressing cells (c-Fos+ cells) in the odor columns of the olfactory bulb (OB). We then measured differences in the proportions of c-Fos-expressing cell types depending on the odor exposure condition. Surprisingly, under the specific odor condition in which the olfactory system was repeatedly exposed to the odorant for 1 min at 5-min intervals, one of the lateral odor columns and the ipsilateral hemisphere of the olfactory tubercle had more c-Fos+ cells than the other three odor columns and the contralateral hemisphere of the olfactory tubercle. However, this interhemispheric asymmetry of c-Fos expression was not observed in the anterior piriform cortex. To confirm whether the anterior olfactory nucleus pars externa (AONpE), which connects the left and right OB, contributes to this asymmetry, AONpE-lesioned mice were analyzed under the specific odor exposure condition. Asymmetric c-Fos expression was not observed in the OB or the olfactory tubercle. These data indicate that the c-Fos expression patterns of the olfactory-related regions in the brain are influenced by the odor exposure condition and that asymmetric c-Fos expression in these regions was observed under a specific odor exposure condition due to synaptic linkage via the AONpE.
Topics: Animals; Brain; Female; Gene Expression; Gene Expression Regulation; Male; Mice; Mice, Inbred C57BL; Neurons; Odorants; Olfactory Bulb; Olfactory Cortex; Olfactory Pathways; Olfactory Perception; Olfactory Tubercle; Proto-Oncogene Proteins c-fos; Smell
PubMed: 32237058
DOI: 10.1002/2211-5463.12851 -
Frontiers in Molecular Neuroscience 2020Trace amine-associated receptors (TAARs) are a class of G-protein-coupled receptors found in mammals. While TAAR1 is expressed in several brain regions, all the other...
Trace amine-associated receptors (TAARs) are a class of G-protein-coupled receptors found in mammals. While TAAR1 is expressed in several brain regions, all the other TAARs have been described mainly in the olfactory epithelium and the glomerular layer of the olfactory bulb and are believed to serve as a new class of olfactory receptors sensing innate odors. However, there is evidence that TAAR5 could play a role also in the central nervous system. In this study, we characterized a mouse line lacking TAAR5 (TAAR5 knockout, TAAR5-KO) expressing beta-galactosidase mapping TAAR5 expression. We found that TAAR5 is expressed not only in the glomerular layer in the olfactory bulb but also in deeper layers projecting to the limbic brain olfactory circuitry with prominent expression in numerous limbic brain regions, such as the anterior olfactory nucleus, the olfactory tubercle, the orbitofrontal cortex (OFC), the amygdala, the hippocampus, the piriform cortex, the entorhinal cortex, the nucleus accumbens, and the thalamic and hypothalamic nuclei. TAAR5-KO mice did not show gross developmental abnormalities but demonstrated less anxiety- and depressive-like behavior in several behavioral tests. TAAR5-KO mice also showed significant decreases in the tissue levels of serotonin and its metabolite in several brain areas and were more sensitive to the hypothermic action of serotonin 5-HT1A receptor agonist 8-hydroxy-2-(di--propilamino)tetralin (8-OH-DPAT). These observations indicate that TAAR5 is not just innate odor-sensing olfactory receptor but also serves to provide olfactory input into limbic brain areas to regulate emotional behaviors likely modulation of the serotonin system. Thus, anxiolytic and/or antidepressant action of future TAAR5 antagonists could be predicted. In general, "olfactory" TAAR-mediated brain circuitry may represent a previously unappreciated neurotransmitter system involved in the transmission of innate odors into emotional behavioral responses.
PubMed: 32194374
DOI: 10.3389/fnmol.2020.00018 -
Proceedings of the National Academy of... Mar 2020The striatal complex of basal ganglia comprises two functionally distinct districts. The dorsal district controls motor and cognitive functions. The ventral district...
The striatal complex of basal ganglia comprises two functionally distinct districts. The dorsal district controls motor and cognitive functions. The ventral district regulates the limbic function of motivation, reward, and emotion. The dorsoventral parcellation of the striatum also is of clinical importance as differential striatal pathophysiologies occur in Huntington's disease, Parkinson's disease, and drug addiction disorders. Despite these striking neurobiologic contrasts, it is largely unknown how the dorsal and ventral divisions of the striatum are set up. Here, we demonstrate that interactions between the two key transcription factors Nolz-1 and Dlx1/2 control the migratory paths of striatal neurons to the dorsal or ventral striatum. Moreover, these same transcription factors control the cell identity of striatal projection neurons in both the dorsal and the ventral striata including the D1-direct and D2-indirect pathways. We show that Nolz-1, through the I12b enhancer, represses , allowing normal migration of striatal neurons to dorsal and ventral locations. We demonstrate that deletion, up-regulation, and down-regulation of and can produce a striatal phenotype characterized by a withered dorsal striatum and an enlarged ventral striatum and that we can rescue this phenotype by manipulating the interactions between Nolz-1 and Dlx1/2 transcription factors. Our study indicates that the two-tier system of striatal complex is built by coupling of cell-type identity and migration and suggests that the fundamental basis for divisions of the striatum known to be differentially vulnerable at maturity is already encoded by the time embryonic striatal neurons begin their migrations into developing striata.
Topics: Animals; Basal Ganglia; Cell Differentiation; Corpus Striatum; Female; Homeodomain Proteins; Interneurons; Intracellular Signaling Peptides and Proteins; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Tissue Proteins; Neurons; Nucleus Accumbens; Transcription Factors; Ventral Striatum
PubMed: 32170006
DOI: 10.1073/pnas.1921007117 -
Annals of Translational Medicine Dec 2019Endometriosis (EM) is a common gynecological disease in women of reproductive age. These patients in approximately 80% suffer the various degree pain. This study will...
BACKGROUND
Endometriosis (EM) is a common gynecological disease in women of reproductive age. These patients in approximately 80% suffer the various degree pain. This study will investigate synergistically the mechanism of the higher-position central sensitization and offer a pre-clinical experiment evidence for treatment of various location-EM patients with pain.
METHODS
Twenty Sprague-Dawley rats were induced three types EM including abdominal EM (n=5), gastrocnemius EM (n=5) and ovary EM group (n=5) and one sham control group (n=5). All groups were measured the pain sensitization by hotplate test, then scanned by the functional magnetic resonance imaging (fMRI). The resting-state fMRI (rs-fMRI) date was analyzed using regional homogeneity (ReHo) approach to find out the abnormal functional activity brain regions. Nissl staining method observed the state of neurons in aberrant ReHo signal brain regions.
RESULTS
Rats with EM pain sensitization were increased in abdominal EM and gastrocnemius EM than ovary EM group and sham control. The ReHo value is decreased in gastrocnemius EM in right thalamus and left olfactory tubercle compared with other three groups. The number of neurons was decreased; cavitation around nucleus, and pyknotic homogenous nuclei. Nissl bodies were stained deeply, and the shape was irregular in gastrocnemius EM by Nissl staining in right thalamus. In left olfactory tubercle, there was no significant difference in 4 groups.
CONCLUSIONS
The thalamus may be the potential key brain region for the central sensitization mechanism of various location-EM pain. The oxidative activation may be weakened in thalamus in gastrocnemius EM group with more severe pain. This finding could lend support for future research on the imageology and pathology of various location-EM pain.
PubMed: 32042783
DOI: 10.21037/atm.2019.11.73 -
Scientific Reports Jan 2020Various neural systems cooperate in feeding behaviour, and olfaction plays crucial roles in detecting and evaluating food objects. While odour-mediated feeding behaviour...
Various neural systems cooperate in feeding behaviour, and olfaction plays crucial roles in detecting and evaluating food objects. While odour-mediated feeding behaviour is highly adaptive and influenced by metabolic state, hedonic cues and learning processes, the underlying mechanism is not well understood. Feeding behaviour is regulated by orexigenic and anorexigenic neuromodulatory molecules. However, knowledge of their roles especially in higher olfactory areas is limited. Given the potentiation of feeding behaviour in hunger state, we systemically examined the expression of feeding-related neuromodulatory molecules in food-restricted mice through quantitative PCR, in the olfactory bulb (OB), olfactory tubercle (OT), and remaining olfactory cortical area (OC). The OT was further divided into attraction-related anteromedial, aversion-related lateral and remaining central regions. Examination of 23 molecules including neuropeptides, opioids, cannabinoids, and their receptors as well as signalling molecules showed that they had different expression patterns, with many showing elevated expression in the OT, especially in the anteromedial and central OT. Further, in mice trained with odour-food association, the expression was significantly altered and the increase or decrease of a given molecule varied among areas. These results suggest that different olfactory areas are regulated separately by feeding-related molecules, which contributes to the adaptive regulation of feeding behaviour.
Topics: Animals; Blood Glucose; Feeding Behavior; Gene Expression Regulation; Insulin; Male; Mice, Inbred C57BL; Neurotransmitter Agents; Odorants; Olfactory Bulb; Olfactory Tubercle; Receptors, Neurotransmitter; Reward; Signal Transduction
PubMed: 31964903
DOI: 10.1038/s41598-020-57605-7 -
Journal of Neurochemistry Feb 2020The ventral striatum is a collection of brain structures, including the nucleus accumbens, ventral pallidum and the olfactory tubercle (OT). While much attention has... (Review)
Review
The ventral striatum is a collection of brain structures, including the nucleus accumbens, ventral pallidum and the olfactory tubercle (OT). While much attention has been devoted to the nucleus accumbens, a comprehensive understanding of the ventral striatum and its contributions to neurological diseases requires an appreciation for the complex neurochemical makeup of the ventral striatum's other components. This review summarizes the rich neurochemical composition of the OT, including the neurotransmitters, neuromodulators and hormones present. We also address the receptors and transporters involved in each system as well as their putative functional roles. Finally, we end with briefly reviewing select literature regarding neurochemical changes in the OT in the context of neurological disorders, specifically neurodegenerative disorders. By overviewing the vast literature on the neurochemical composition of the OT, this review will serve to aid future research into the neurobiology of the ventral striatum.
Topics: Animals; Humans; Olfactory Tubercle; Ventral Striatum
PubMed: 31755104
DOI: 10.1111/jnc.14919