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Nature Neuroscience Dec 2021The striatum comprises multiple subdivisions and neural circuits that differentially control motor output. The islands of Calleja (IC) contain clusters of densely packed...
The striatum comprises multiple subdivisions and neural circuits that differentially control motor output. The islands of Calleja (IC) contain clusters of densely packed granule cells situated in the ventral striatum, predominantly in the olfactory tubercle (OT). Characterized by expression of the D3 dopamine receptor, the IC are evolutionally conserved, but have undefined functions. Here, we show that optogenetic activation of OT D3 neurons robustly initiates self-grooming in mice while suppressing other ongoing behaviors. Conversely, optogenetic inhibition of these neurons halts ongoing grooming, and genetic ablation reduces spontaneous grooming. Furthermore, OT D3 neurons show increased activity before and during grooming and influence local striatal output via synaptic connections with neighboring OT neurons (primarily spiny projection neurons), whose firing rates display grooming-related modulation. Our study uncovers a new role of the ventral striatum's IC in regulating motor output and has important implications for the neural control of grooming.
Topics: Animals; Corpus Striatum; Grooming; Islands of Calleja; Mice; Neurons; Olfactory Tubercle; Ventral Striatum
PubMed: 34795450
DOI: 10.1038/s41593-021-00952-z -
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 -
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 -
Current Biology : CB Dec 2021Medium spiny neurons (MSNs) constitute the vast majority of striatal neurons and the principal interface between dopamine reward signals and functionally diverse...
Medium spiny neurons (MSNs) constitute the vast majority of striatal neurons and the principal interface between dopamine reward signals and functionally diverse cortico-basal ganglia circuits. Information processing in these circuits is dependent on distinct MSN types: cell types that are traditionally defined according to their projection targets or dopamine receptor expression. Single-cell transcriptional studies have revealed greater MSN heterogeneity than predicted by traditional circuit models, but the transcriptional landscape in the primate striatum remains unknown. Here, we set out to establish molecular definitions for MSN subtypes in Rhesus monkeys and to explore the relationships between transcriptionally defined subtypes and anatomical subdivisions of the striatum. Our results suggest at least nine MSN subtypes, including dorsal striatum subtypes associated with striosome and matrix compartments, ventral striatum subtypes associated with the nucleus accumbens shell and olfactory tubercle, and an MSN-like cell type restricted to μ-opioid receptor rich islands in the ventral striatum. Although each subtype was demarcated by discontinuities in gene expression, continuous variation within subtypes defined gradients corresponding to anatomical locations and, potentially, functional specializations. These results lay the foundation for achieving cell-type-specific transgenesis in the primate striatum and provide a blueprint for investigating circuit-specific information processing.
Topics: Animals; Corpus Striatum; Dopamine; Mice; Mice, Inbred C57BL; Neostriatum; Neurons; Primates
PubMed: 34727523
DOI: 10.1016/j.cub.2021.10.015 -
Nature Neuroscience Nov 2021The basolateral amygdala (BLA) plays essential roles in behaviors motivated by stimuli with either positive or negative valence, but how it processes motivationally...
The basolateral amygdala (BLA) plays essential roles in behaviors motivated by stimuli with either positive or negative valence, but how it processes motivationally opposing information and participates in establishing valence-specific behaviors remains unclear. Here, by targeting Fezf2-expressing neurons in the BLA, we identify and characterize two functionally distinct classes in behaving mice, the negative-valence neurons and positive-valence neurons, which innately represent aversive and rewarding stimuli, respectively, and through learning acquire predictive responses that are essential for punishment avoidance or reward seeking. Notably, these two classes of neurons receive inputs from separate sets of sensory and limbic areas, and convey punishment and reward information through projections to the nucleus accumbens and olfactory tubercle, respectively, to drive negative and positive reinforcement. Thus, valence-specific BLA neurons are wired with distinctive input-output structures, forming a circuit framework that supports the roles of the BLA in encoding, learning and executing valence-specific motivated behaviors.
Topics: Amygdala; Animals; Attention; Avoidance Learning; Corpus Striatum; DNA-Binding Proteins; Female; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Motivation; Nerve Net; Nerve Tissue Proteins
PubMed: 34663958
DOI: 10.1038/s41593-021-00927-0 -
Foods (Basel, Switzerland) Aug 2021The anterior insula and rolandic operculum are key regions for flavour perception in the human brain; however, it is unclear how taste and congruent retronasal smell are...
The anterior insula and rolandic operculum are key regions for flavour perception in the human brain; however, it is unclear how taste and congruent retronasal smell are perceived as flavours. The multisensory integration required for sour flavour perception has rarely been studied; therefore, we investigated the brain responses to taste and smell in the sour flavour-processing network in 35 young healthy adults. We aimed to characterise the brain response to three stimulations applied in the oral cavity-sour taste, retronasal smell of mango, and combined flavour of both-using functional magnetic resonance imaging. Effective connectivity of the flavour-processing network and modulatory effect from taste and smell were analysed. Flavour stimulation activated middle insula and olfactory tubercle (primary taste and olfactory cortices, respectively); anterior insula and rolandic operculum, which are associated with multisensory integration; and ventrolateral prefrontal cortex, a secondary cortex for flavour perception. Dynamic causal modelling demonstrated that neural taste and smell signals were integrated at anterior insula and rolandic operculum. These findings elucidated how neural signals triggered by sour taste and smell presented in liquid form interact in the brain, which may underpin the neurobiology of food appreciation. Our study thus demonstrated the integration and synergy of taste and smell.
PubMed: 34574144
DOI: 10.3390/foods10092034 -
International Journal of Molecular... Aug 2021Mammalian transglutaminases (TGs) catalyze calcium-dependent irreversible posttranslational modifications of proteins and their enzymatic activities contribute to the...
Mammalian transglutaminases (TGs) catalyze calcium-dependent irreversible posttranslational modifications of proteins and their enzymatic activities contribute to the pathogenesis of several human neurodegenerative diseases. Although different transglutaminases are found in many different tissues, the TG6 isoform is mostly expressed in the CNS. The present study was embarked on/undertaken to investigate expression, distribution and activity of transglutaminases in Huntington disease transgenic rodent models, with a focus on analyzing the involvement of TG6 in the age- and genotype-specific pathological features relating to disease progression in HD transgenic mice and a tgHD transgenic rat model using biochemical, histological and functional assays. Our results demonstrate the physical interaction between TG6 and (mutant) huntingtin by co-immunoprecipitation analysis and the contribution of its enzymatic activity for the total aggregate load in SH-SY5Y cells. In addition, we identify that TG6 expression and activity are especially abundant in the olfactory tubercle and piriform cortex, the regions displaying the highest amount of mHTT aggregates in transgenic rodent models of HD. Furthermore, mHTT aggregates were colocalized within TG6-positive cells. These findings point towards a role of TG6 in disease pathogenesis via mHTT aggregate formation.
Topics: Animals; Disease Models, Animal; Huntingtin Protein; Huntington Disease; Mice; Mice, Transgenic; Mutant Proteins; Mutation; Neurons; Rats; Transglutaminases
PubMed: 34445621
DOI: 10.3390/ijms22168914 -
International Journal of Molecular... May 2021is one of the most interesting genes regulated by thyroid hormones that, through the inhibition of the striatal cAMP/PKA pathway, acts as a modulator of dopamine... (Review)
Review
is one of the most interesting genes regulated by thyroid hormones that, through the inhibition of the striatal cAMP/PKA pathway, acts as a modulator of dopamine neurotransmission. is expressed at high levels in the dorsal striatum, with a medial-to-lateral expression gradient reflecting that of both dopamine D and adenosine A receptors. transcript is also present in the hippocampus, cerebral cortex, olfactory tubercle and bulb, substantia nigra pars compacta (SNc) and ventral tegmental area of the rodent brain. In line with -dependent regulation of dopaminergic transmission, data showed that lack of enhanced cocaine- and amphetamine-induced motor stimulation in mice. Previous studies showed that pharmacological depletion of dopamine significantly reduces mRNA levels in rodents, non-human primates and Parkinson's disease (PD) patients, suggesting a link between dopaminergic innervation and physiological mRNA expression. Rhes protein binds to and activates striatal mTORC1, and modulates L-DOPA-induced dyskinesia in PD rodent models. Finally, Rhes is involved in the survival of mouse midbrain dopaminergic neurons of SNc, thus pointing towards a Rhes-dependent modulation of autophagy and mitophagy processes, and encouraging further investigations about mechanisms underlying dysfunctions of the nigrostriatal system.
Topics: Animals; Autophagy; Brain; Corpus Striatum; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Dopaminergic Neurons; GTP-Binding Proteins; Gene Expression Regulation; Humans; Levodopa; Mice; Mice, Knockout; Mitophagy; Models, Neurological; Nerve Degeneration; Parkinson Disease; Parkinsonian Disorders; RNA, Messenger; Signal Transduction; Synaptic Transmission
PubMed: 34070217
DOI: 10.3390/ijms22105326 -
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 -
Biology Letters Apr 2021Developmental studies of brain volumes can reveal which portions of neural circuits are sensitive to environmental inputs. In social insects, differences in relative...
Developmental studies of brain volumes can reveal which portions of neural circuits are sensitive to environmental inputs. In social insects, differences in relative investment across brain regions emerge as behavioural repertoires change during ontogeny or as a result of experience. Here, we test the effects of maturation and social experience on morphological brain development in paper wasps focusing on brain regions involved in visual and olfactory processing. We find that mature wasps regardless of social experience have relatively larger brains than newly emerged wasps and this difference is driven by changes to mushroom body calyx and visual regions but not olfactory processing neuropils. Notably, social wasps invest more in the anterior optic tubercle (AOT), a visual glomerulus involved in colour and object processing in other taxa, relative to other visual integration centres the mushroom body calyces compared with aged socially naive wasps. Differences in developmental plasticity between visual and olfactory neuropil volumes are discussed in light of behavioural maturation in paper wasps, especially as it relates to social recognition. Previous research has shown that need social experience to develop specialized visual processing of faces, which is used to individually recognize conspecifics. The present study suggests that the AOT is a candidate brain region that could mediate facial processing in this species.
Topics: Animals; Brain; Cognition; Recognition, Psychology; Wasps
PubMed: 33849349
DOI: 10.1098/rsbl.2021.0073