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Frontiers in Neuroanatomy 2017Understanding of the olfactory neural circuits has progressed beyond analysis of how odor information from the external environment is processed in the brain. While... (Review)
Review
Understanding of the olfactory neural circuits has progressed beyond analysis of how odor information from the external environment is processed in the brain. While spatially-organized sub-circuits were found to exist up to the olfactory bulb (OB), the arrangement in the olfactory cortex (OC), especially in its representative piriform cortex (PC), appears diffuse and dispersed. An emerging view is that the activity of OC neurons may not simply encode odor identity but rather encode plastic odor information such as odor value. Although many studies support this notion, odor value can be either positive or negative, and the existence of sub-circuits corresponding to individual value types is not well explored. To address this question, I introduce here two olfactory areas other than the PC, OB and olfactory tubercle (OT) whose analysis may facilitate understanding of functional sub-circuits related to different odor values. Peripheral and centrifugal inputs to the OB are considered to relate to odor identity and odor value, respectively and centrifugal inputs to the OB potentially represent different odor values during different behavioral periods. The OT has spatially-segregated functional domains related to distinct motivated and hedonic behaviors. Thus, the OT provides a good starting point from which functional sub-circuits across various olfactory regions can be traced. Further analysis across wide areas of the olfactory system will likely reveal the functional sub-circuits that link odor identity with distinct odor values and direct distinct odor-induced motivated and hedonic behaviors.
PubMed: 28443001
DOI: 10.3389/fnana.2017.00033 -
ENeuro 2019The inter-regional connectivity of sensory structures in the brain allows for the modulation of sensory processing in manners important for perception. In the olfactory...
The inter-regional connectivity of sensory structures in the brain allows for the modulation of sensory processing in manners important for perception. In the olfactory system, odor representations in the olfactory bulb (OB) are modulated by feedback centrifugal innervation from several olfactory cortices, including the piriform cortex (PCX) and anterior olfactory nucleus (AON). Previous studies reported that an additional olfactory cortex, the olfactory tubercle (OT), also centrifugally innervates the OB and may even shape the activity of OB output neurons. In an attempt to identify the cell types of this centrifugal innervation, we performed retrograde tracing experiments in mice utilizing three unique strategies, including retrobeads, retrograde adeno-associated virus (AAV) driving a fluorescent reporter, and retrograde AAV driving Cre-expression in the Ai9-floxed transgenic reporter line. Our results replicated the standing literature and uncovered robustly labeled neurons in the ipsilateral PCX, AON, and numerous other structures known to innervate the OB. Surprisingly, consistent throughout all of our approaches, no labeled soma were observed in the OT. These findings indicate that the OT is unique among other olfactory cortices in that it does not innervate the OB, which refines our understanding of the centrifugal modulation of the OB.
Topics: Animals; Female; Male; Mice, Inbred C57BL; Mice, Transgenic; Neuroanatomical Tract-Tracing Techniques; Olfactory Bulb; Olfactory Pathways
PubMed: 30740517
DOI: 10.1523/ENEURO.0390-18.2019 -
ELife Jun 2022Positive and negative associations acquired through olfactory experience are thought to be especially strong and long-lasting. The conserved direct olfactory sensory...
Positive and negative associations acquired through olfactory experience are thought to be especially strong and long-lasting. The conserved direct olfactory sensory input to the ventral striatal olfactory tubercle (OT) and its convergence with dense dopaminergic input to the OT could underlie this privileged form of associative memory, but how this process occurs is not well understood. We imaged the activity of the two canonical types of striatal neurons, expressing D1- or D2-type dopamine receptors, in the OT at cellular resolution while mice learned odor-outcome associations ranging from aversive to rewarding. D1 and D2 neurons both responded to rewarding and aversive odors. D1 neurons in the OT robustly and bidirectionally represented odor valence, responding similarly to odors predicting similar outcomes regardless of odor identity. This valence representation persisted even in the absence of a licking response to the odors and in the absence of the outcomes, indicating a true transformation of odor sensory information by D1 OT neurons. In contrast, D2 neuronal representation of the odor-outcome associations was weaker, contingent on a licking response by the mouse, and D2 neurons were more selective for odor identity than valence. Stimulus valence coding in the OT was modality-sensitive, with separate sets of D1 neurons responding to odors and sounds predicting the same outcomes, suggesting that integration of multimodal valence information happens downstream of the OT. Our results point to distinct representation of identity and valence of odor stimuli by D1 and D2 neurons in the OT.
Topics: Animals; Cues; Mice; Neurons; Odorants; Olfactory Tubercle; Receptors, Dopamine D2; Smell; Ventral Striatum
PubMed: 35708179
DOI: 10.7554/eLife.75463 -
Neurochemical Research Jun 2021Activation of dopamine (DA) neurons is essential for the transition from sleep to wakefulness and maintenance of awakening, and sufficient to accelerate the emergence...
Activation of dopamine (DA) neurons is essential for the transition from sleep to wakefulness and maintenance of awakening, and sufficient to accelerate the emergence from general anesthesia in animals. Dopamine receptors (DR) are involve in arousal mediation. In the present study, we showed that the olfactory tubercle (OT) was active during emergence from isoflurane anesthesia, local injection of dopamine D1 receptor (D1R) agonist chloro-APB (1 mg/mL) and D2 receptor (D2R) agonist quinpirole (1 mg/mL) into OT enhanced behavioural and cortical arousal from isoflurane anesthesia, while D1R antagonist SCH-23390 (1 mg/mL) and D2R antagonist raclopride (2.5 mg/mL) prolonged recovery time. Optogenetic activation of DAergic terminals in OT also promoted behavioural and cortical arousal from isoflurane anesthesia. However, neither D1R/D2R agonists nor D1R/D2R antagonists microinjection had influences on the induction of isoflurane anesthesia. Optogenetic stimulation on DAergic terminals in OT also had no impact on the anesthesia induction. Our results indicated that DA signals in OT accelerated emergence from isoflurane anesthesia. Furthermore, the induction of general anesthesia, different from the emergence process, was not mediated by the OT DAergic pathways.
Topics: Anesthetics, Inhalation; Animals; Arousal; Benzazepines; Dopamine Agonists; Dopamine D2 Receptor Antagonists; Isoflurane; Male; Mice, Inbred C57BL; Olfactory Tubercle; Quinpirole; Raclopride; Receptors, Dopamine D1; Receptors, Dopamine D2; Mice
PubMed: 33710536
DOI: 10.1007/s11064-021-03291-4 -
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 -
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 -
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 -
Journal of Neurochemistry Apr 2022The olfactory tubercle (OT), an important component of the ventral striatum and limbic system, is involved in multi-sensory integration of reward-related information in...
The olfactory tubercle (OT), an important component of the ventral striatum and limbic system, is involved in multi-sensory integration of reward-related information in the brain. However, its functional roles are often overshadowed by the neighboring nucleus accumbens. Increasing evidence has highlighted that dense dopamine (DA) innervation of the OT from the ventral tegmental area (VTA) is implicated in encoding reward, natural reinforcers, and motivated behaviors. Recent studies have further suggested that OT subregions may have distinct roles in these processes due to their heterogeneous DA transmission. Currently, very little is known about regulation (release and clearance) of extracellular DA across OT subregions due to its limited anatomical accessibility and proximity to other DA-rich brain regions, making it difficult to isolate VTA-DA signaling in the OT with conventional methods. Herein, we characterized heterogeneous VTA-DA regulation in the medial (m) and lateral (l) OT in "wild-type," urethane-anesthetized rats by integrating in vivo fast-scan cyclic voltammetry with cell-type specific optogenetics to stimulate VTA-DA neurons. Channelrhodopsin-2 was selectively expressed in the VTA-DA neurons of wild-type rats and optical stimulating parameters were optimized to determine VTA-DA transmission across the OT. Our anatomical, neurochemical, and pharmacological results show that VTA-DA regulation in the mOT is less dependent on DA transporters and has greater DA transmission than the lOT. These findings establish the OT as a unique, compartmentalized structure and will aid in future behavioral characterization of the roles of VTA-DA signaling in the OT subregions in reward, drug addiction, and encoding behavioral outputs necessary for survival.
Topics: Animals; Dopamine; Nucleus Accumbens; Olfactory Tubercle; Optogenetics; Rats; Ventral Tegmental Area
PubMed: 35061915
DOI: 10.1111/jnc.15577 -
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