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Frontiers in Neural Circuits 2020Olfaction plays an important role in the evaluation, motivation, and palatability of food. The chemical identity of odorants is coded by a spatial combination of... (Review)
Review
Olfaction plays an important role in the evaluation, motivation, and palatability of food. The chemical identity of odorants is coded by a spatial combination of activated glomeruli in the olfactory bulb, which is referred to as the odor map. However, the functional roles of the olfactory cortex, a collective region that receives axonal projections from the olfactory bulb, and higher olfactory centers in odor-guided eating behaviors are yet to be elucidated. The olfactory tubercle (OT) is a component of the ventral striatum and forms a node within the mesolimbic dopaminergic pathway. Recent studies have revealed the anatomical domain structures of the OT and their functions in distinct odor-guided motivated behaviors. Another component of the ventral striatum, the nucleus accumbens, is well known for its involvement in motivation and hedonic responses for foods, which raises the possibility of functional similarities between the OT and nucleus accumbens in eating. This review first summarizes recent findings on the domain- and neuronal subtype-specific roles of the OT in odor-guided motivated behaviors and then proposes a model for the regulation of eating behaviors by the OT.
Topics: Animals; Feeding Behavior; Humans; Motivation; Nucleus Accumbens; Odorants; Olfactory Tubercle
PubMed: 33262693
DOI: 10.3389/fncir.2020.577880 -
Molecular and Cellular Neurosciences Jul 2019The olfactory tubercle (OT) is located in the ventral-medial region of the brain where it receives primary input from olfactory bulb (OB) projection neurons and...
The olfactory tubercle (OT) is located in the ventral-medial region of the brain where it receives primary input from olfactory bulb (OB) projection neurons and processes olfactory behaviors related to motivation, hedonics of smell and sexual encounters. The OT is part of the dopamine reward system that shares characteristics with the striatum. Together with the nucleus accumbens, the OT has been referred to as the "ventral striatum". However, despite its functional importance little is known about the embryonic development of the OT and the phenotypic properties of the OT cells. Here, using thymidine analogs, we establish that mouse OT neurogenesis occurs predominantly between E11-E15 in a lateral-to-medial gradient. Then, using a piggyBac multicolor technique we characterized the migratory route of OT neuroblasts from their embryonic point of origin. Following neurogenesis in the ventral lateral ganglionic eminence (vLGE), neuroblasts destined for the OT followed a dorsal-ventral pathway we named "ventral migratory course" (VMC). Upon reaching the nascent OT, neurons established a prototypical laminar distribution that was determined, in part, by the progenitor cell of origin. A phenotypic analysis of OT neuroblasts using a single-color piggyBac technique, showed that OT shared the molecular specification of striatal neurons. In addition to primary afferent input from the OB, the OT also receives a robust dopaminergic input from ventral tegmentum (Ikemoto, 2007). We used tyrosine hydroxylase (TH) expression as a proxy for dopaminergic innervation and showed that TH onset occurs at E13 and progressively increased until postnatal stages following an 'inside-out' pattern. Postnatally, we established the myelination in the OT occurring between P7 and P14, as shown with CNPase staining, and we characterized the cellular phenotypes populating the OT by immunohistochemistry. Collectively, this work provides the first detailed analysis of the developmental and maturation processes occurring in mouse OT, and demonstrates the striatal nature of the OT as part of the ventral striatum (vST).
Topics: Animals; Dopaminergic Neurons; Female; Male; Mice; Myelin Sheath; Neurogenesis; Olfactory Tubercle
PubMed: 31200100
DOI: 10.1016/j.mcn.2019.06.002 -
Chemical Senses Sep 2016Modern neuroscience often relies upon artistic renderings to illustrate key aspects of anatomy. These renderings can be in 2 or even 3 dimensions. Three-dimensional... (Review)
Review
Modern neuroscience often relies upon artistic renderings to illustrate key aspects of anatomy. These renderings can be in 2 or even 3 dimensions. Three-dimensional renderings are especially helpful in conceptualizing highly complex aspects of neuroanatomy which otherwise are not visually apparent in 2 dimensions or even intact biological samples themselves. Here, we provide 3 dimensional renderings of the gross- and cellular-anatomy of the rodent olfactory tubercle. Based upon standing literature and detailed investigations into rat brain specimens, we created biologically inspired illustrations of the olfactory tubercle in 3 dimensions as well as its connectivity with olfactory bulb projection neurons, the piriform cortex association fiber system, and ventral pallidum medium spiny neurons. Together, we intend for these illustrations to serve as a resource to the neuroscience community in conceptualizing and discussing this highly complex and interconnected brain system with established roles in sensory processing and motivated behaviors.
Topics: Animals; Olfactory Tubercle; Rats; Ventral Striatum
PubMed: 27340137
DOI: 10.1093/chemse/bjw069 -
Neural Regeneration Research Nov 2023Sleep benefits the restoration of energy metabolism and thereby supports neuronal plasticity and cognitive behaviors. Sirt6 is a NAD-dependent protein deacetylase that...
Sleep benefits the restoration of energy metabolism and thereby supports neuronal plasticity and cognitive behaviors. Sirt6 is a NAD-dependent protein deacetylase that has been recognized as an essential regulator of energy metabolism because it modulates various transcriptional regulators and metabolic enzymes. The aim of this study was to investigate the influence of Sirt6 on cerebral function after chronic sleep deprivation (CSD). We assigned C57BL/6J mice to control or two CSD groups and subjected them to AAV2/9-CMV-EGFP or AAV2/9-CMV-Sirt6-EGFP infection in the prelimbic cortex (PrL). We then assessed cerebral functional connectivity (FC) using resting-state functional MRI, neuron/astrocyte metabolism using a metabolic kinetics analysis; dendritic spine densities using sparse-labeling; and miniature excitatory postsynaptic currents (mEPSCs) and action potential (AP) firing rates using whole-cell patch-clamp recordings. In addition, we evaluated cognition via a comprehensive set of behavioral tests. Compared with controls, Sirt6 was significantly decreased (P < 0.05) in the PrL after CSD, accompanied by cognitive deficits and decreased FC between the PrL and accumbens nucleus, piriform cortex, motor cortex, somatosensory cortex, olfactory tubercle, insular cortex, and cerebellum. Sirt6 overexpression reversed CSD-induced cognitive impairment and reduced FC. Our analysis of metabolic kinetics using [1-C] glucose and [2-C] acetate showed that CSD reduced neuronal Glu and GABA synthesis, which could be fully restored via forced Sirt6 expression. Furthermore, Sirt6 overexpression reversed CSD-induced decreases in AP firing rates as well as the frequency and amplitude of mEPSCs in PrL pyramidal neurons. These data indicate that Sirt6 can improve cognitive impairment after CSD by regulating the PrL-associated FC network, neuronal glucose metabolism, and glutamatergic neurotransmission. Thus, Sirt6 activation may have potential as a novel strategy for treating sleep disorder-related diseases.
PubMed: 37282476
DOI: 10.4103/1673-5374.371370 -
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 -
Brain Research Aug 2016In the early 1980's, the dispute on the existence of a multiplicity of receptors for neurotransmitter was at its height. Several subtypes of serotonin (5-HT) receptors... (Review)
Review
UNLABELLED
In the early 1980's, the dispute on the existence of a multiplicity of receptors for neurotransmitter was at its height. Several subtypes of serotonin (5-HT) receptors were proposed on the basis of radioligand binding assays. In order to provide further support to the existence of these receptors we performed quantitative autoradiographic mapping of the binding of several ligands for the 5-HT1 receptor labeling the subtypes 5-HT1A, 5-HT1B and 5-HT1C, and characterized pharmacologically these different receptors. The results demonstrated differential localization of the subtypes of 5-HT1 receptors indicating that they were expressed by different cell populations, probably neurons, in the brain and further supporting their reality. Shortly afterwards, the cloning of the genes coding for these 5-HT receptors, and many others, ended the dispute by demonstrating that they were different proteins. The advent of Molecular Biology provided new methodologies for the study of the chemical and molecular anatomy of 5-HT receptors in brain, by visualizing cells expressing their mRNA by in situ hybridization and showed that the family of mammalian 5-HT receptors has 14 members, a figure much larger than ever suspected at that time.
ORIGINAL ARTICLE ABSTRACT
QUANTITATIVE AUTORADIOGRAPHIC MAPPING OF SEROTONIN RECEPTORS IN THE RAT BRAIN. I. SEROTONIN-1 RECEPTORS: The distribution of serotonin-1 (5-HT1) receptors in the rat brain was studied by light microscopic quantitative autoradiography. Receptors were labeled with [(3)H]serotonin (5-[(3)H]HT), 8-hydroxy-2-[H-dipropylamino-(3)H]tetralin (8-OH-[(3)H]DPAT), [(3)H]LSD and [(3)H]mesulergine, and the densities quantified by microdensitometry with the aid of a computer-assisted image-analysis system. Competition experiments for 5-[(3)H]HT binding by several serotonin-1 agonizts led to the identification of brain areas enriched in each one of the three subtypes of 5-HT1 recognition sites already described (5-HT1A, 5-HT1B, 5-HT1C). The existence of these׳selective׳ areas allowed a detailed pharmacological characterization of these sites to be made in a more precise manner than has been attained in membrane-binding studies. While 5-[(3)H]HT labeled with nanomolar affinity all the 5-HT1 subtypes, the other (3)H-labeled ligands labeled selectively 5-HT1A (8-OH-[(3)H]DPAT), 5-HT1C ([(3)H]mesulergine) and both of them ([(3)H]LSD). Very high concentrations of 5-HT1 receptors were localized in the choroid plexus, lateroseptal nucleus, globus pallidus and ventral pallidum, dentate gyrus, dorsal subiculum, olivary pretectal nucleus, substantia nigra, reticular and external layer of the entorhinal cortex. The different fields of the hippocampus (CA1-CA4), some nuclei of the amygdaloid complex, the hypothalamic nuclei and the dorsal raphé, among others, also presented high concentrations of sites. Areas containing intermediate densities of 5-HT1 receptors included the claustrum, olfactory tubercle, accumbens, central gray and lateral cerebellar nucleus. The nucleus caudate-putamen and the cortex, at the different levels studied, presented receptor densities ranging from intermediate to low. Finally, in other brain areas-pons, medulla, and spinal cord-only low or very low concentrations of 5-HT1 receptors were found. From the areas strongly enriched in 5-HT1 sites, dentate gyrus and septal nucleus contained 5-HT1A sites, while globus pallidus, dorsal subiculum, substantia nigra and olivary pretectal nucleus were enriched in 5-HT1B. The sites in the choroid plexus, which presented the highest density of receptors in the rat brain, were of the 5-HT1C subtype. The distribution of 5-HT1 receptors reported here is discussed in correlation with the distribution of serotoninergic neurons and fibers, the related anatomical pathways and the effects which appear to be mediated by these sites. © 1985.This article is part of a Special Issue entitled SI:50th Anniversary Issue. This article is part of a Special Issue entitled SI:50th Anniversary Issue.
Topics: Animals; Autoradiography; Brain; Choroid Plexus; History, 20th Century; Humans; In Situ Hybridization; Neurons; Neurosciences; Rats; Receptors, Serotonin, 5-HT1
PubMed: 26740406
DOI: 10.1016/j.brainres.2015.12.042 -
The Journal of Neuroscience : the... Jan 2022The human sense of smell plays an important role in appetite and food intake, detecting environmental threats, social interactions, and memory processing. However,...
The human sense of smell plays an important role in appetite and food intake, detecting environmental threats, social interactions, and memory processing. However, little is known about the neural circuity supporting its function. The olfactory tracts project from the olfactory bulb along the base of the frontal cortex, branching into several striae to meet diverse cortical regions. Historically, using diffusion magnetic resonance imaging (dMRI) to reconstruct the human olfactory tracts has been prevented by susceptibility and motion artifacts. Here, we used a dMRI method with readout segmentation of long variable echo-trains (RESOLVE) to minimize image distortions and characterize the human olfactory tracts We collected high-resolution dMRI data from 25 healthy human participants (12 male and 13 female) and performed probabilistic tractography using constrained spherical deconvolution (CSD). At the individual subject level, we identified the lateral, medial, and intermediate striae with their respective cortical connections to the piriform cortex and amygdala (AMY), olfactory tubercle (OT), and anterior olfactory nucleus (AON). We combined individual results across subjects to create a normalized, probabilistic atlas of the olfactory tracts. We then investigated the relationship between olfactory perceptual scores and measures of white matter integrity, including mean diffusivity (MD). Importantly, we found that olfactory tract MD negatively correlated with odor discrimination performance. In summary, our results provide a detailed characterization of the connectivity of the human olfactory tracts and demonstrate an association between their structural integrity and olfactory perceptual function. This study provides the first detailed description of the cortical connectivity of the three olfactory tract striae in the human brain, using diffusion magnetic resonance imaging (dMRI). Additionally, we show that tract microstructure correlates with performance on an odor discrimination task, suggesting a link between the structural integrity of the olfactory tracts and odor perception. Lastly, we generated a normalized probabilistic atlas of the olfactory tracts that may be used in future research to study its integrity in health and disease.
Topics: Adult; Diffusion Magnetic Resonance Imaging; Female; Humans; Image Processing, Computer-Assisted; Male; Olfactory Bulb; Olfactory Pathways
PubMed: 34759031
DOI: 10.1523/JNEUROSCI.1552-21.2021 -
Journal of Neural Transmission (Vienna,... Oct 2015We interact with the physical world through our senses, and these aid our behavioral performance and various activities of life. Sensory information is transmitted in... (Review)
Review
We interact with the physical world through our senses, and these aid our behavioral performance and various activities of life. Sensory information is transmitted in neuronal networks, and the brain optimally interprets the external and internal milieu/environment. This paper delineates the framework in which the pathogenesis of memory and cognitive dysfunction is underpinned by sensory olfactory dysfunction. ERC is the gateway for olfactory input to the hippocampus, and there is seamless synchronization between sensory function and hippocampal activity. Transmission of olfactory information to the hippocampus is sequential-it is projected from the olfactory receptors to olfactory bulb to the primary olfactory cortex (comprised the anterior olfactory nucleus, the olfactory tubercle, and the piriform cortex) to the entorhinal cortex (ERC). Through perforant pathway ERC enables olfactory inputs to effectively excite hippocampal neurons. One of the earliest pathological changes in Alzheimer's disease (AD) include the olfactory dysfunction and the atrophy in ERC and hippocampus (rate in ERC is higher than in the hippocampus). Olfactory dysfunction negatively impacts the ERC and the deafferenting of the hippocampus from olfactory inputs upregulates memory decline. Olfactory dysfunction, therefore, is an important and early correlate of AD pathology. A number of factors described here may cause olfactory dysfunction; this may lead to hypoperfusion, hypometabolism, impaired synaptic transmission, and variable atrophy in olfaction-related regions. Improvement in olfactory function, therefore, is an important goal in order to attenuate cognitive neuropathology in aging and AD. This article seeks to provide a comprehensive and balanced overview of olfactory neuropathology in incipient AD, and suggests strategies to enhance olfactory function and ameliorate cognitive decline.
Topics: Alzheimer Disease; Animals; Brain; Disease Progression; Humans; Olfaction Disorders; Olfactory Perception
PubMed: 25944089
DOI: 10.1007/s00702-015-1404-6 -
Frontiers in Neural Circuits 2022The olfactory tubercle (OT) is a striatal region that receives olfactory inputs. mRNAs of prodynorphin (Pdyn) and preproenkephalin (Penk), precursors of dynorphins and...
The olfactory tubercle (OT) is a striatal region that receives olfactory inputs. mRNAs of prodynorphin (Pdyn) and preproenkephalin (Penk), precursors of dynorphins and enkephalins, respectively, are strongly expressed in the striatum. Both produce opioid peptides with various physiological effects such as pain relief and euphoria. Recent studies have revealed that OT has anatomical and cytoarchitectonic domains that play different roles in odor-induced motivated behavior. Neuronal subtypes of the OT can be distinguished by their expression of the dopamine receptors D1 (Drd1) and D2 (Drd2). Here, we addressed whether and which type of opioid peptide precursors the D1- and D2-expressing neurons in the OT express. We used multiple fluorescence hybridization for mRNAs of the opioid precursors and dopamine receptors to characterize mouse OT neurons. Pdyn was mainly expressed by Drd1-expressing cells in the dense cell layer (DCL) of the OT, whereas Penk was expressed primarily by Drd2-expressing cells in the DCL. We also confirmed the presence of a larger population of Pdyn-Penk-Drd1 co-expressing cells in the DCL of the anteromedial OT compared with the anterolateral OT. These observations will help understand whether and how dynorphins and enkephalins in the OT are involved in diverse odor-induced motivated behaviors.
Topics: Animals; Corpus Striatum; Dynorphins; Enkephalins; In Situ Hybridization, Fluorescence; Mice; Neurons; Olfactory Tubercle; Protein Precursors; RNA, Messenger; Receptors, Dopamine D1
PubMed: 35937204
DOI: 10.3389/fncir.2022.908964 -
Frontiers in Neuroanatomy 2015New neurons are continually generated in the subependymal layer of the lateral ventricles and the subgranular zone of dentate gyrus during adulthood. In the...
New neurons are continually generated in the subependymal layer of the lateral ventricles and the subgranular zone of dentate gyrus during adulthood. In the subventricular zone, neuroblasts migrate a long distance to the olfactory bulb where they differentiate into granule or periglomerular interneurons. In the hippocampus, neuroblasts migrate a short distance from the subgranular zone to the granule cell layer of the dentate gyrus to become granule neurons. In addition to the short-distance inputs, bulbar interneurons receive long-distance centrifugal afferents from olfactory-recipient structures. Similarly, dentate granule cells receive differential inputs from the medial and lateral entorhinal cortices through the perforant pathway. Little is known concerning these new inputs on the adult-born cells. In this work, we have characterized afferent inputs to 21-day old newly-born neurons. Mice were intraperitoneally injected with bromodeoxyuridine. Two weeks later, rhodamine-labeled dextran-amine was injected into the anterior olfactory nucleus, olfactory tubercle, piriform cortex and lateral and medial entorhinal cortices. One week later, animals were perfused and immunofluorescences were carried out. The data show that projection neurons from the mentioned structures, establish putative synaptic contacts onto 21-day-old neurons in the olfactory bulb and dentate gyrus, in some cases even before they start to express specific subpopulation proteins. Long-distance afferents reach middle and outer one-third portions of the molecular layer of the dentate gyrus and granule and, interestingly, periglomerular layers of the olfactory bulb. In the olfactory bulb, these fibers appear to establish presumptive axo-somatic contacts onto newly-born granule and periglomerular cells.
PubMed: 25698936
DOI: 10.3389/fnana.2015.00004