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Frontiers in Neural Circuits 2017The medial part of the olfactory tubercle (OT) is a brain structure located at the interface of the reward and olfactory system. It is closely related to...
The medial part of the olfactory tubercle (OT) is a brain structure located at the interface of the reward and olfactory system. It is closely related to pheromone-rewards, natural reinforcement, addiction and many other behaviors. However, the structure of the anatomic circuitry of the medial part of the OT is still unclear. In the present study, the medial part of the OT was found to be highly connected with a wide range of brain areas with the help of the pseudorabies virus tracing tool. In order to further investigate the detailed connections for specific neurons, another tracing tool - rabies virus was utilized for D1R-cre and D2R-cre mice. The D1R and D2R neurons in the medial part of the OT were both preferentially innervated by the olfactory areas, especially the piriform cortex, and both had similar direct input patterns. With the help of the adeno-associated virus labeling, it was found that the two subpopulations of neurons primarily innervate with the reward related brain regions, with slightly less axons projecting to the olfactory areas. Thus, the whole-brain input and output circuitry structures for specific types of neurons in the medial part of the OT were systematically investigated, and the results revealed many unique connecting features. This work could provide new insights for further study into the physiological functions of the medial part of the OT.
Topics: Animals; Male; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Confocal; Neuroanatomical Tract-Tracing Techniques; Neurons; Olfactory Pathways; Olfactory Tubercle; Receptors, Dopamine D1; Receptors, Dopamine D2
PubMed: 28804450
DOI: 10.3389/fncir.2017.00052 -
The Journal of Neuroscience : the... Jan 2016The ventral striatum is critical for evaluating reward information and the initiation of goal-directed behaviors. The many cellular, afferent, and efferent similarities...
UNLABELLED
The ventral striatum is critical for evaluating reward information and the initiation of goal-directed behaviors. The many cellular, afferent, and efferent similarities between the ventral striatum's nucleus accumbens and olfactory tubercle (OT) suggests the distributed involvement of neurons within the ventral striatopallidal complex in motivated behaviors. Although the nucleus accumbens has an established role in representing goal-directed actions and their outcomes, it is not known whether this function is localized within the nucleus accumbens or distributed also within the OT. Answering such a fundamental question will expand our understanding of the neural mechanisms underlying motivated behaviors. Here we address whether the OT encodes natural reinforcers and serves as a substrate for motivational information processing. In recordings from mice engaged in a novel water-motivated instrumental task, we report that OT neurons modulate their firing rate during initiation and progression of the instrumental licking behavior, with some activity being internally generated and preceding the first lick. We further found that as motivational drive decreases throughout a session, the activity of OT neurons is enhanced earlier relative to the behavioral action. Additionally, OT neurons discriminate the types and magnitudes of fluid reinforcers. Together, these data suggest that the processing of reward information and the orchestration of goal-directed behaviors is a global principle of the ventral striatum and have important implications for understanding the neural systems subserving addiction and mood disorders.
SIGNIFICANCE STATEMENT
Goal-directed behaviors are widespread among animals and underlie complex behaviors ranging from food intake, social behavior, and even pathological conditions, such as gambling and drug addiction. The ventral striatum is a neural system critical for evaluating reward information and the initiation of goal-directed behaviors. Here we show that neurons in the olfactory tubercle subregion of the ventral striatum robustly encode the onset and progression of motivated behaviors, and discriminate the type and magnitude of a reward. Our findings are novel in showing that olfactory tubercle neurons participate in such coding schemes and are in accordance with the principle that ventral striatum substructures may cooperate to guide motivated behaviors.
Topics: Action Potentials; Animals; Appetitive Behavior; Goals; Male; Mice; Mice, Inbred C57BL; Motivation; Neurons; Olfactory Tubercle; Reward; Statistics, Nonparametric; Ventral Striatum
PubMed: 26758844
DOI: 10.1523/JNEUROSCI.3328-15.2016 -
Brain Research Jul 1998The goal of this study was to support the hypothesis that visceral signals may integrate and influence behavior by way of direct pathways from the nucleus tractus...
The goal of this study was to support the hypothesis that visceral signals may integrate and influence behavior by way of direct pathways from the nucleus tractus solitarii (NTS) to the olfactory tubercle and the midline/intralaminar thalamus. An anterograde tracer, biotinylated dextran amine (BDA) was iontophoresed bilaterally into the caudal NTS to optimize terminal labeling. NTS-cortical projections traversed both limbs of the diagonal bands providing heavy innervation, and terminated lightly within layer 3 of the olfactory tubercle. NTS-thalamic projections terminated within anterior and, as previously shown, posterior divisions of nucleus paraventricularis thalami and avoided the adjoining mediodorsal thalamic nucleus. Heretofore unrecognized projections were traced to the parafascicular and reuniens thalamic nuclei, and the peripeduncular nucleus. Control experiments identified the nucleus gracilis as the principal source of ascending projections to ventroposterior lateral, posterior and intralaminar thalamic nuclei. Our data corroborate the supposition that olfactory signals may integrate with visceral stimuli in the striatal compartment of olfactory tubercle. NTS projections encompass thalamic nuclei that project topographically to the prefrontal cortex, hippocampus and ventral (limbic) striatum, regions activated by visceral stimulation. Structural data support the idea that compartments of the non-discriminative thalamus may contribute to perception and behavioral responses to visceral stimulation.
Topics: Afferent Pathways; Animals; Behavior, Animal; Biotin; Brain Mapping; Dextrans; Fluorescent Dyes; Olfactory Bulb; Rats; Rats, Sprague-Dawley; Solitary Nucleus; Synaptic Transmission; Thalamus; Viscera
PubMed: 9666113
DOI: 10.1016/s0006-8993(98)00442-9 -
The Journal of Comparative Neurology Oct 2011The olfactory peduncle, the region connecting the olfactory bulb with the basal forebrain, contains several neural areas that have received relatively little attention....
The olfactory peduncle, the region connecting the olfactory bulb with the basal forebrain, contains several neural areas that have received relatively little attention. The present work includes studies that provide an overview of the region in the mouse. An analysis of cell soma size in pars principalis (pP) of the anterior olfactory nucleus (AON) revealed considerable differences in tissue organization between mice and rats. An unbiased stereological study of neuron number in the cell-dense regions of pars externa (pE) and pP of the AON of 3-, 12-, and 24-month-old mice indicated that pE has about 16,500 cells in 0.043 mm(3) and pP about 58,300 cells in 0.307 mm(3) . Quantitative Golgi studies of pyramidal neurons in pP suggested that mouse neurons are similar to although smaller than those of the rat. An immunohistochemical analysis demonstrated that all peduncular regions (pE, pP, the dorsal peduncular cortex, ventral tenia tecta, and anterior olfactory tubercle and piriform cortex) have cells that express either calbindin, calretinin, parvalbumin, somatostatin, vasoactive intestinal polypeptide, neuropeptide Y, or cholecystokinin (antigens commonly co-expressed by subspecies of γ-aminobutyric acid [GABA]ergic neurons), although the relative numbers of each cell type differ between zones. Finally, an electron microscopic comparison of the organization of myelinated fibers in lateral olfactory tract in the anterior and posterior peduncle indicated that the region is less orderly in mice than in rats. The results provide a caveat for investigators who generalize data between species, as both similarities and differences between the laboratory mouse and rat were observed.
Topics: Animals; Cell Shape; Male; Mice; Mice, Inbred C57BL; Olfactory Bulb; Olfactory Pathways; Olfactory Receptor Neurons; Prosencephalon; Rats
PubMed: 21618219
DOI: 10.1002/cne.22662 -
Frontiers in Neuroanatomy 2021The uptake, transmission and processing of sensory olfactory information is modulated by inhibitory and excitatory receptors in the olfactory system. Previous studies...
The uptake, transmission and processing of sensory olfactory information is modulated by inhibitory and excitatory receptors in the olfactory system. Previous studies have focused on the function of individual receptors in distinct brain areas, but the receptor architecture of the whole system remains unclear. Here, we analyzed the receptor profiles of the whole olfactory system of adult male mice. We examined the distribution patterns of glutamatergic (AMPA, kainate, mGlu, and NMDA), GABAergic (GABA, GABA, and GABA), dopaminergic (D) and noradrenergic (α and α) neurotransmitter receptors by quantitative receptor autoradiography combined with an analysis of the cyto- and myelo-architecture. We observed that each subarea of the olfactory system is characterized by individual densities of distinct neurotransmitter receptor types, leading to a region- and layer-specific receptor profile. Thereby, the investigated receptors in the respective areas and strata showed a heterogeneous expression. Generally, we detected high densities of mGluRs, GABARs and GABARs. Noradrenergic receptors revealed a highly heterogenic distribution, while the dopaminergic receptor D displayed low concentrations, except in the olfactory tubercle and the dorsal endopiriform nucleus. The similarities and dissimilarities of the area-specific multireceptor profiles were analyzed by a hierarchical cluster analysis. A three-cluster solution was found that divided the areas into the (1) olfactory relay stations (main and accessory olfactory bulb), (2) the olfactory cortex (anterior olfactory cortex, dorsal peduncular cortex, taenia tecta, piriform cortex, endopiriform nucleus, entorhinal cortex, orbitofrontal cortex) and the (3) olfactory tubercle, constituting its own cluster. The multimodal receptor-architectonic analysis of each component of the olfactory system provides new insights into its neurochemical organization and future possibilities for pharmaceutic targeting.
PubMed: 33967704
DOI: 10.3389/fnana.2021.632549 -
ELife Jul 2019The central processing pathways of the human olfactory system are not fully understood. The olfactory bulb projects directly to a number of cortical brain structures,...
The central processing pathways of the human olfactory system are not fully understood. The olfactory bulb projects directly to a number of cortical brain structures, but the distinct networks formed by projections from each of these structures to the rest of the brain have not been well-defined. Here, we used functional magnetic resonance imaging and k-means clustering to parcellate human primary olfactory cortex into clusters based on whole-brain functional connectivity patterns. Resulting clusters accurately corresponded to anterior olfactory nucleus, olfactory tubercle, and frontal and temporal piriform cortices, suggesting dissociable whole-brain networks formed by the subregions of primary olfactory cortex. This result was replicated in an independent data set. We then characterized the unique functional connectivity profiles of each subregion, producing a map of the large-scale processing pathways of the human olfactory system. These results provide insight into the functional and anatomical organization of the human olfactory system.
Topics: Adult; Anatomy, Artistic; Atlases as Topic; Female; Humans; Male; Nerve Net; Olfactory Cortex; Olfactory Pathways
PubMed: 31339489
DOI: 10.7554/eLife.47177 -
The Journal of Neuroscience : the... Feb 2010Historical and psychophysical literature has demonstrated a perceptual interplay between olfactory and auditory stimuli-the neural mechanisms of which are not...
Historical and psychophysical literature has demonstrated a perceptual interplay between olfactory and auditory stimuli-the neural mechanisms of which are not understood. Here, we report novel findings revealing that the early olfactory code is subjected to auditory cross-modal influences. In vivo extracellular recordings from the olfactory tubercle, a trilaminar structure within the basal forebrain, of anesthetized mice revealed that olfactory tubercle single units selectively respond to odors-with 65% of units showing significant odor-evoked activity. Remarkably, 19% of olfactory tubercle single units also showed robust responses to an auditory tone. Furthermore, 29% of single units tested displayed supraadditive or suppressive responses to the simultaneous presentation of odor and tone, suggesting cross-modal modulation. In contrast, olfactory bulb units did not show significant responses to tone presentation nor modulation of odor-evoked activity by tone-suggesting a lack of olfactory-auditory convergence upstream from the olfactory tubercle. Thus, the tubercle presents itself as a source for direct multimodal convergence within an early stage of odor processing and may serve as a seat for psychophysical interactions between smells and sounds.
Topics: Acoustic Stimulation; Action Potentials; Animals; Association; Auditory Pathways; Auditory Perception; Auditory Threshold; Electrophysiology; Hearing; Male; Mice; Odorants; Olfactory Pathways; Olfactory Perception; Psychophysics; Sensory Receptor Cells; Smell; Structure-Activity Relationship
PubMed: 20181598
DOI: 10.1523/JNEUROSCI.6003-09.2010 -
Anatomical Record (Hoboken, N.J. : 2007) Sep 2013Impaired olfaction has been described as an early symptom in Alzheimer's disease (AD). Neuroanatomical changes underlying this deficit in the olfactory system are...
Impaired olfaction has been described as an early symptom in Alzheimer's disease (AD). Neuroanatomical changes underlying this deficit in the olfactory system are largely unknown. Given that interneuron populations are crucial in olfactory information processing, we have quantitatively analyzed somatostatin- (SOM), parvalbumin- (PV), and calretinin-expressing (CR) cells in the olfactory bulb, anterior olfactory nucleus, and olfactory tubercle in PS1 x APP double transgenic mice model of AD. The experiments were performed in wild type and double transgenic homozygous animal groups of 2, 4, 6, and 8 months of age to analyze early stages of the pathology. In addition, beta-amyloid (Aβ) expression and its correlation with SOM cells have been quantified under confocal microscopy. The results indicate increasing expressions of Aβ with aging as well as an early fall of SOM and CR expression, whereas PV was decreased later in the disease progression. These observations evidence an early, preferential vulnerability of SOM and CR cells in rostral olfactory structures during AD that may be useful to unravel neural basis of olfactory deficits associated to this neurodegenerative disorder.
Topics: Age Factors; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Calbindin 2; Disease Models, Animal; Disease Progression; Female; Homozygote; Humans; Interneurons; Mice; Mice, Transgenic; Olfactory Bulb; Olfactory Pathways; Parvalbumins; Presenilin-1; Smell; Somatostatin; Time Factors
PubMed: 23904197
DOI: 10.1002/ar.22750 -
Neuropsychiatric Disease and Treatment 2019Different literature reviews of gambling disorder (GD) neurobiology have been focused on human studies, others have focused on rodents, and others combined human and... (Review)
Review
Different literature reviews of gambling disorder (GD) neurobiology have been focused on human studies, others have focused on rodents, and others combined human and rodent studies. The main question of this review was: which are the main neurotransmitters systems and brain structures relevant for GD based on recent rodent studies? This work aims to review the experimental findings regarding the rodent´s neurobiology of GD. A search in the Pub Med database was set (October 2012-October 2017) and 162 references were obtained. After screening, 121 references were excluded, and only 41 references remained from the initial output. More, other 25 references were added to complement (introduction section, neuroanatomical descriptions) the principal part of the work. At the end, a total of 66 references remained for the review. The main conclusions are: 1) according to studies that used noninvasive methods for drug administration, some of the neurotransmitters and receptors involved in behaviors related to GD are: muscarinic, N-methyl-D-aspartate (NMDA), cannabinoid receptor 1 (CB), cannabinoid receptor 2 (CB), dopamine 2 receptor (D), dopamine 3 receptor (D), and dopamine 4 receptor (D); 2) moreover, there are other neurotransmitters and receptors involved in GD based on studies that use invasive methods of drug administration (eg, brain microinjection); example of these are: serotonin 1A receptor (5-HT), noradrenaline receptors, gamma-aminobutyric acid receptor A (GABA), and gamma-aminobutyric acid receptor B (GABA); 3) different brain structures are relevant to behaviors linked to GD, like: amygdala (including basolateral amygdala (BLA)), anterior cingulate cortex (ACC), hippocampus, infralimbic area, insular cortex (anterior and rostral agranular), nucleus accumbens (NAc), olfactory tubercle (island of Calleja), orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), prefrontal cortex (PFC) - subcortical network, striatum (ventral) and the subthalamic nucleus (STN); and 4) the search for GD treatments should consider this diversity of receptor/neurotransmitter systems and brain areas.
PubMed: 31308669
DOI: 10.2147/NDT.S192746 -
Brain Pathology (Zurich, Switzerland) Jul 2017Autism Spectrum Disorder is characterized by sensory anomalies including impaired olfactory identification. Between 5 and 46 percent of individuals with autism have a...
Autism Spectrum Disorder is characterized by sensory anomalies including impaired olfactory identification. Between 5 and 46 percent of individuals with autism have a clinical diagnosis of epilepsy. Primary olfactory cortex (piriform cortex) is central to olfactory identification and is an epileptogenic structure. Cytoarchitectural changes in olfactory cortex may underlie olfactory differences seen in autism. Primary olfactory cortex was sampled from 17 post-mortem autism cases with and without epilepsy, 11 epilepsy cases without autism and 11 typically developed cases. Stereological and neuropathological methods were used to quantify glial, pyramidal and non-pyramidal cell densities in layers of the piriform as well as identify pathological differences in this area and its neighbouring region, the olfactory tubercle. We found increased layer II glial cell densities in autism with and without epilepsy, which were negatively correlated with age and positively correlated with levels of corpora amylacea in layer I. These changes were also associated with greater symptom severity and did not extend to the olfactory tubercle. Glial cell organization may follow an altered trajectory of development with age in autism. The findings are consistent with other studies implicating increased glial cells in the autism brain. Altered cytoarchitecture may contribute to sensory deficits observed in affected individuals. This study provides evidence that autism is linked to alterations in the cytoarchitectural structure that underlies primary sensory processes and is not restricted to heteromodal ("higher") cognitive centers.
Topics: Adolescent; Adult; Age Factors; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Autistic Disorder; Epilepsy; Female; Glial Fibrillary Acidic Protein; Humans; Male; Middle Aged; Neuroglia; Neurons; Olfactory Cortex; Postmortem Changes; Severity of Illness Index; Statistics as Topic; Young Adult
PubMed: 27409070
DOI: 10.1111/bpa.12415