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Neuropharmacology May 2020The olfactory tubercle (OT), an important nucleus in processing sensory information, has been reported to change cortical activity under odor. However, little is known...
The olfactory tubercle (OT), an important nucleus in processing sensory information, has been reported to change cortical activity under odor. However, little is known about the physiological role and mechanism of the OT in sleep-wake regulation. The OT expresses abundant adenosine A receptors (ARs), which are important in sleep regulation. Therefore, we hypothesized that the OT regulates sleep via ARs. This study examined sleep-wake profiles through electroencephalography and electromyography recordings with pharmacological and chemogenetic manipulations in freely moving rodents. Compared with their controls, activation of OT ARs pharmacologically and OT AR neurons via chemogenetics increased non-rapid eye movement sleep for 5 and 3 h, respectively, while blockade of ARs decreased non-rapid eye movement sleep. Tracing and electrophysiological studies showed OT AR neurons projected to the ventral pallidum and lateral hypothalamus, forming inhibitory innervations. Together, these findings indicate that ARs in the OT play an important role in sleep regulation.
Topics: Adenosine; Adenosine A2 Receptor Agonists; Animals; Electroencephalography; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Olfactory Tubercle; Phenethylamines; Rats; Rats, Sprague-Dawley; Receptor, Adenosine A2A; Rodentia; Sleep
PubMed: 31874169
DOI: 10.1016/j.neuropharm.2019.107923 -
Brain Research Jul 2014Rats selectively bred for high- and low-capacity for running on a treadmill (HCR; LCR) also differ in wheel-running behavior, but whether wheel-running can be explained...
UNLABELLED
Rats selectively bred for high- and low-capacity for running on a treadmill (HCR; LCR) also differ in wheel-running behavior, but whether wheel-running can be explained by intrinsic or adaptive brain mechanisms is not as yet understood. It is established that motivation of locomotory behavior is driven by dopaminergic transmission in mesolimbic and mesostriatal systems. However, whether voluntary wheel running is associated with enkephalinergic activity in the ventral striatum is not known.
MATERIALS AND METHODS
40 male (20 HCR and 20 LCR) and 40 female (20 HCR and 20 LCR) rats were randomly assigned to 3 weeks of activity wheel exposure or sedentary conditions without wheel access. After 3 weeks of activity-wheel running, rats were decapitated and brains were extracted. Coronal sections were analyzed utilizing in situ hybridization histochemistry for enkephalin (ENK) mRNA in the ventral striatum.
RESULTS
HCR rats expressed less ENK than LCR rats in the nucleus accumbens among females (p<0.01) and in the olfactory tubercle among both females (p<0.05) and males (p<0.05). There was no effect of wheel running on ENK mRNA expression.
CONCLUSION
Line differences in ENK expression in the olfactory tubercle, and possibly the nucleus accumbens, partly explain divergent wheel-running behavior. The lower striatal ENK in the HCR line is consistent with enhanced dopaminergic tone, which may explain the increased motivation for wheel running observed in the HCR line.
Topics: Animals; Enkephalins; Female; Male; Motor Activity; Nucleus Accumbens; Olfactory Tubercle; RNA, Messenger; Rats; Running; Ventral Striatum
PubMed: 24842004
DOI: 10.1016/j.brainres.2014.05.014 -
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 -
The Journal of Neuroscience : the... Mar 2015Sensory information acquires meaning to adaptively guide behaviors. Despite odors mediating a number of vital behaviors, the components of the olfactory system...
Sensory information acquires meaning to adaptively guide behaviors. Despite odors mediating a number of vital behaviors, the components of the olfactory system responsible for assigning meaning to odors remain unclear. The olfactory tubercle (OT), a ventral striatum structure that receives monosynaptic input from the olfactory bulb, is uniquely positioned to transform odor information into behaviorally relevant neural codes. No information is available, however, on the coding of odors among OT neurons in behaving animals. In recordings from mice engaged in an odor discrimination task, we report that the firing rate of OT neurons robustly and flexibly encodes the valence of conditioned odors over identity, with rewarded odors evoking greater firing rates. This coding of rewarded odors occurs before behavioral decisions and represents subsequent behavioral responses. We predict that the OT is an essential region whereby odor valence is encoded in the mammalian brain to guide goal-directed behaviors.
Topics: Animals; Discrimination Learning; Male; Mice; Mice, Inbred C57BL; Odorants; Olfactory Tubercle; Smell; Ventral Striatum
PubMed: 25788670
DOI: 10.1523/JNEUROSCI.4750-14.2015 -
Experimental Neurology Jul 2019Traumatic brain injury (TBI) affects at least 3 M people annually. In humans, repetitive mild TBI (rmTBI) can lead to increased impulsivity and may be associated with...
Repetitive closed-head impact model of engineered rotational acceleration (CHIMERA) injury in rats increases impulsivity, decreases dopaminergic innervation in the olfactory tubercle and generates white matter inflammation, tau phosphorylation and degeneration.
Traumatic brain injury (TBI) affects at least 3 M people annually. In humans, repetitive mild TBI (rmTBI) can lead to increased impulsivity and may be associated with chronic traumatic encephalopathy. To better understand the relationship between repetitive TBI (rTBI), impulsivity and neuropathology, we used CHIMERA (Closed-Head Injury Model of Engineered Rotational Acceleration) to deliver five TBIs to rats, which were continuously assessed for trait impulsivity using the delay discounting task and for neuropathology at endpoint. Compared to sham controls, rats with rTBI displayed progressive impairment in impulsive choice. Histological analyses revealed reduced dopaminergic innervation from the ventral tegmental area to the olfactory tubercle, consistent with altered impulsivity neurocircuitry. Consistent with diffuse axonal injury generated by CHIMERA, white matter inflammation, tau immunoreactivity and degeneration were observed in the optic tract and corpus callosum. Finally, pronounced grey matter microgliosis was observed in the olfactory tubercle. Our results provide insight into the mechanisms by which rTBI leads to post-traumatic psychiatric-like symptoms in a novel rat TBI platform.
Topics: Animals; Axons; Choice Behavior; Corpus Callosum; Disease Models, Animal; Dopaminergic Neurons; Gliosis; Head Injuries, Closed; Inflammation; Male; Neurodegenerative Diseases; Olfactory Tubercle; Phosphorylation; Rats; Rats, Long-Evans; Reward; Tauopathies; White Matter; tau Proteins
PubMed: 30822421
DOI: 10.1016/j.expneurol.2019.02.012 -
The Journal of Comparative Neurology Apr 2020In the cerebellum, GluD2 is exclusively expressed in Purkinje cells, where it regulates synapse formation and regeneration, synaptic plasticity, and motor learning....
In the cerebellum, GluD2 is exclusively expressed in Purkinje cells, where it regulates synapse formation and regeneration, synaptic plasticity, and motor learning. Delayed cognitive development in humans with GluD2 gene mutations suggests extracerebellar functions of GluD2. However, extracerebellar expression of GluD2 and its relationship with that of GluD1 are poorly understood. GluD2 mRNA and protein were widely detected, with relatively high levels observed in the olfactory glomerular layer, medial prefrontal cortex, cingulate cortex, retrosplenial granular cortex, olfactory tubercle, subiculum, striatum, lateral septum, anterodorsal thalamic nucleus, and arcuate hypothalamic nucleus. These regions were also enriched for GluD1, and many individual neurons coexpressed the two GluDs. In the retrosplenial granular cortex, GluD1 and GluD2 were selectively expressed at PSD-95-expressing glutamatergic synapses, and their coexpression on the same synapses was shown by SDS-digested freeze-fracture replica labeling. Biochemically, GluD1 and GluD2 formed coimmunoprecipitable complex formation in HEK293T cells and in the cerebral cortex and hippocampus. We further estimated the relative protein amount by quantitative immunoblotting using GluA2/GluD2 and GluA2/GluD1 chimeric proteins as standards for titration of GluD1 and GluD2 antibodies. Intriguingly, the relative amount of GluD2 was almost comparable to that of GluD1 in the postsynaptic density fraction prepared from the cerebral cortex and hippocampus. In contrast, GluD2 was overwhelmingly predominant in the cerebellum. Thus, we have determined the relative extracerebellar expression of GluD1 and GluD2 at regional, neuronal, and synaptic levels. These data provide a molecular-anatomical basis for possible competitive and cooperative interactions of GluD family members at synapses in various brain regions.
Topics: Animals; Brain; Gene Expression Profiling; Glutamate Dehydrogenase; HEK293 Cells; Humans; Mice; Mice, Inbred C57BL; Receptors, Glutamate
PubMed: 31625608
DOI: 10.1002/cne.24792 -
Nature Communications Nov 2021Immunolabeling and autoradiography have traditionally been applied as the methods-of-choice to visualize and collect molecular information about physiological and...
Immunolabeling and autoradiography have traditionally been applied as the methods-of-choice to visualize and collect molecular information about physiological and pathological processes. Here, we introduce PharmacoSTORM super-resolution imaging that combines the complementary advantages of these approaches and enables cell-type- and compartment-specific nanoscale molecular measurements. We exploited rational chemical design for fluorophore-tagged high-affinity receptor ligands and an enzyme inhibitor; and demonstrated broad PharmacoSTORM applicability for three protein classes and for cariprazine, a clinically approved antipsychotic and antidepressant drug. Because the neurobiological substrate of cariprazine has remained elusive, we took advantage of PharmacoSTORM to provide in vivo evidence that cariprazine predominantly binds to D dopamine receptors on Islands of Calleja granule cell axons but avoids dopaminergic terminals. These findings show that PharmacoSTORM helps to quantify drug-target interaction sites at the nanoscale level in a cell-type- and subcellular context-dependent manner and within complex tissue preparations. Moreover, the results highlight the underappreciated neuropsychiatric significance of the Islands of Calleja in the ventral forebrain.
Topics: Animals; Brain; Female; Islands of Calleja; Male; Mice; Mice, Inbred C57BL; Piperazines; Receptors, Dopamine D2; Receptors, Dopamine D3
PubMed: 34764251
DOI: 10.1038/s41467-021-26757-z -
Neurosurgery Jun 2020The subthalamic nucleus (STN), globus pallidus internus (GPi), and pedunculopontine nucleus (PPN) are effective targets for deep brain stimulation (DBS) in many...
BACKGROUND
The subthalamic nucleus (STN), globus pallidus internus (GPi), and pedunculopontine nucleus (PPN) are effective targets for deep brain stimulation (DBS) in many pathological conditions. Previous literature has focused on appropriate stimulation targets and their relationships with functional neuroanatomic pathways; however, comprehensive anatomic dissections illustrating these nuclei and their connections are lacking. This information will provide insight into the anatomic basis of stimulation-induced DBS benefits and side effects.
OBJECTIVE
To combine advanced cadaveric dissection techniques and ultrahigh field magnetic resonance imaging (MRI) to explore the anatomy of the STN, GPi, and PPN with their associated fiber pathways.
METHODS
A total of 10 cadaveric human brains and 2 hemispheres of a cadaveric head were examined using fiber dissection techniques. The anatomic dissections were compared with 11.1 Tesla (T) structural MRI and 4.7 T MRI fiber tractography.
RESULTS
The extensive connections of the STN (caudate nucleus, putamen, medial frontal cortex, substantia innominata, substantia nigra, PPN, globus pallidus externus (GPe), GPi, olfactory tubercle, hypothalamus, and mammillary body) were demonstrated. The connections of GPi to the thalamus, substantia nigra, STN, amygdala, putamen, PPN, and GPe were also illustrated. The PPN was shown to connect to the STN and GPi anteriorly, to the cerebellum inferiorly, and to the substantia nigra anteriorly and superiorly.
CONCLUSION
This study demonstrates connections using combined anatomic microdissections, ultrahigh field MRI, and MRI tractography. The anatomic findings are analyzed in relation to various stimulation-induced clinical effects. Precise knowledge of neuroanatomy, anatomic relationships, and fiber connections of the STN, GPi, PPN will likely enable more effective targeting and improved DBS outcomes.
Topics: Autopsy; Deep Brain Stimulation; Dissection; Globus Pallidus; Humans; Magnetic Resonance Imaging; Pedunculopontine Tegmental Nucleus; Subthalamic Nucleus; Thalamus
PubMed: 31504849
DOI: 10.1093/neuros/nyz318 -
Brain, Behavior and Evolution 2019Living holosteans, comprising 8 species of bowfins and gars, form a small monophyletic group of actinopterygian fishes, which are currently considered as the sister... (Comparative Study)
Comparative Study
Living holosteans, comprising 8 species of bowfins and gars, form a small monophyletic group of actinopterygian fishes, which are currently considered as the sister group to the enormously numerous teleosts and have largely been neglected in neuroanatomical studies. We have studied the catecholaminergic (CAergic) systems by means of antibodies against tyrosine hydroxylase (TH) and dopamine (DA) in the brain of representative species of the 3 genera included in the 2 orders of holostean fishes: Amia calva (Amiiformes) and Lepisosteus platyrhincus, Lepisosteus oculatus, and Atractosteus spatula (Lepisosteiformes). Different groups of TH/DA-immunoreactive (ir) cells were observed in the olfactory bulb, subpallium, and preoptic area of the telencephalon. Hypothalamic groups were labeled in the suprachiasmatic nucleus, tuberal (only in A. calva), retrotuberal, and retromamillary areas; specifically, the paraventricular organ showed only DA immunoreactivity. In the diencephalon, TH/DA-ir groups were detected in the prethalamus, posterior tubercle, and pretectum. In the caudal hindbrain, the solitary tract nucleus and area postrema presented TH/DA-ir cell groups, and also the spinal cord and the retina. Only in A. calva, particular CAergic cell groups were observed in the habenula, the mesencephalic tegmentum, and in the locus coeruleus. Following a neuromeric analysis, the comparison of these results with those obtained in other classes of fishes and tetrapods shows many common traits of CAergic systems shared by most vertebrates and in addition highlights unique features of actinopterygian fishes.
Topics: Animals; Brain; Catecholamines; Fishes; Neurons; Retina; Spinal Cord
PubMed: 31711060
DOI: 10.1159/000503769 -
Emotion (Washington, D.C.) Sep 2016Disgust is an emotion that helps us deal with potential contamination (Rozin & Fallon, 1987). It produces a distinctive facial expression (e.g., wrinkled nose) and a...
Disgust is an emotion that helps us deal with potential contamination (Rozin & Fallon, 1987). It produces a distinctive facial expression (e.g., wrinkled nose) and a physiological response that is accompanied by strong visceral sensations (e.g., nausea). Given the important role that the anterior insula plays in processing and integrating visceral information (Craig, 2009), it is likely to be centrally involved in disgust. Despite this, few studies have examined the link between insular degeneration and the experience, physiology, and expression of disgust. We studied a group that was heterogeneous in terms of insular damage: 84 patients with neurodegenerative diseases (i.e., frontotemporal dementia, corticobasal syndrome, progressive supranuclear palsy, Alzheimer's disease) and 29 controls. Subjects viewed films that elicit high levels of disgust and sadness. Emotional reactivity was assessed using self-report, peripheral physiology, and facial behavior. Regional brain volumes (insula, putamen, pallidum, caudate, and amygdala) were determined from structural MRIs using the FreeSurfer method. Results indicated that smaller insular volumes were associated with reduced disgust responding in self-report and physiological reactivity, but not in facial behavior. In terms of the specificity of these findings, insular volume did not predict sadness reactivity, and disgust reactivity was not predicted by putamen, pallidum, and caudate volumes (lower self-reported disgust was associated with smaller amygdala volume). These findings underscore the central role of the insula in the experience and physiology of disgust. (PsycINFO Database Record
Topics: Aged; Emotions; Female; Humans; Islands of Calleja; Male; Middle Aged; Neurodegenerative Diseases
PubMed: 27148847
DOI: 10.1037/emo0000195