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1.
Med Hypotheses ; 156: 110688, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34628112

RESUMO

Depression is the second leading cause of disability in the world. Despite developing some efficacious treatments, many patients do not respond to the treatment well due to the complexity of depression and unknown mechanisms involved in its pathogenesis. It has been reported that patients with major depressive disorder (MDD) experience autonomic dysfunctions in different aspects. Evidence suggests that modulation of the autonomic nervous system may improve depression. Von Economo neurons (VENs) are shown to be involved in the pathophysiology of some of the neurological and psychological diseases. VENs are also important for the "ego" formation, sense of empathy, intuition, and cognition. These neurons express a high level of adrenoreceptor alpha 1a, which confirms their role in the autonomic function. Here, based on some evidence, I propose the hypothesis that these neurons may play a role in depression, possibly through being involved in the autonomic function. More focused studies on VENs and their possible role in depression is suggested in future. This pathway may open a new window in the treatment of depression.


Assuntos
Transtorno Depressivo Maior , Sistema Nervoso Autônomo , Depressão , Humanos , Vias Neurais , Neurônios
2.
Nat Commun ; 12(1): 5185, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465771

RESUMO

Parkinson's disease (PD) is characterised by the emergence of beta frequency oscillatory synchronisation across the cortico-basal-ganglia circuit. The relationship between the anatomy of this circuit and oscillatory synchronisation within it remains unclear. We address this by combining recordings from human subthalamic nucleus (STN) and internal globus pallidus (GPi) with magnetoencephalography, tractography and computational modelling. Coherence between supplementary motor area and STN within the high (21-30 Hz) but not low (13-21 Hz) beta frequency range correlated with 'hyperdirect pathway' fibre densities between these structures. Furthermore, supplementary motor area activity drove STN activity selectively at high beta frequencies suggesting that high beta frequencies propagate from the cortex to the basal ganglia via the hyperdirect pathway. Computational modelling revealed that exaggerated high beta hyperdirect pathway activity can provoke the generation of widespread pathological synchrony at lower beta frequencies. These findings suggest a spectral signature and a pathophysiological role for the hyperdirect pathway in PD.


Assuntos
Vias Neurais , Doença de Parkinson/fisiopatologia , Estudos de Coortes , Globo Pálido/química , Globo Pálido/fisiopatologia , Humanos , Magnetoencefalografia , Córtex Motor/química , Córtex Motor/fisiopatologia , Núcleo Subtalâmico/química , Núcleo Subtalâmico/fisiopatologia
3.
Elife ; 102021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34468312

RESUMO

Escape from threats has paramount importance for survival. However, it is unknown if a single circuit controls escape vigor from innate and conditioned threats. Cholecystokinin (cck)-expressing cells in the hypothalamic dorsal premammillary nucleus (PMd) are necessary for initiating escape from innate threats via a projection to the dorsolateral periaqueductal gray (dlPAG). We now show that in mice PMd-cck cells are activated during escape, but not other defensive behaviors. PMd-cck ensemble activity can also predict future escape. Furthermore, PMd inhibition decreases escape speed from both innate and conditioned threats. Inhibition of the PMd-cck projection to the dlPAG also decreased escape speed. Intriguingly, PMd-cck and dlPAG activity in mice showed higher mutual information during exposure to innate and conditioned threats. In parallel, human functional magnetic resonance imaging data show that a posterior hypothalamic-to-dlPAG pathway increased activity during exposure to aversive images, indicating that a similar pathway may possibly have a related role in humans. Our data identify the PMd-dlPAG circuit as a central node, controlling escape vigor elicited by both innate and conditioned threats.


Assuntos
Comportamento Animal , Condicionamento Psicológico , Reação de Fuga , Medo , Hipotálamo Posterior/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Adulto , Animais , Mapeamento Encefálico , Colecistocinina/genética , Colecistocinina/metabolismo , Feminino , Humanos , Hipotálamo Posterior/diagnóstico por imagem , Hipotálamo Posterior/metabolismo , Imageamento por Ressonância Magnética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Vias Neurais/fisiologia , Optogenética , Substância Cinzenta Periaquedutal/diagnóstico por imagem , Substância Cinzenta Periaquedutal/metabolismo , Estimulação Luminosa , Ratos Long-Evans , Fatores de Tempo , Gravação em Vídeo , Percepção Visual , Adulto Jovem
4.
Elife ; 102021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34542408

RESUMO

Prioritizing memory for valuable information can promote adaptive behavior across the lifespan, but it is unclear how the neurocognitive mechanisms that enable the selective acquisition of useful knowledge develop. Here, using a novel task coupled with functional magnetic resonance imaging, we examined how children, adolescents, and adults (N = 90) learn from experience what information is likely to be rewarding, and modulate encoding and retrieval processes accordingly. We found that the ability to use learned value signals to selectively enhance memory for useful information strengthened throughout childhood and into adolescence. Encoding and retrieval of high- vs. low-value information was associated with increased activation in striatal and prefrontal regions implicated in value processing and cognitive control. Age-related increases in value-based lateral prefrontal cortex modulation mediated the relation between age and memory selectivity. Our findings demonstrate that developmental increases in the strategic engagement of the prefrontal cortex support the emergence of adaptive memory.


Assuntos
Desenvolvimento do Adolescente , Aprendizagem por Associação , Desenvolvimento Infantil , Cognição , Memória , Vias Neurais/crescimento & desenvolvimento , Córtex Pré-Frontal/crescimento & desenvolvimento , Adolescente , Adulto , Fatores Etários , Mapeamento Encefálico , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/diagnóstico por imagem , Testes Neuropsicológicos , Córtex Pré-Frontal/diagnóstico por imagem , Adulto Jovem
6.
Int J Mol Sci ; 22(15)2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34361077

RESUMO

In mammalian reproduction, sexually active males seek female conspecifics, while estrous females try to approach males. This sex-specific response tendency is called sexual preference. In small rodents, sexual preference cues are mainly chemosensory signals, including pheromones. In this article, we review the physiological mechanisms involved in sexual preference for opposite-sex chemosensory signals in well-studied laboratory rodents, mice, rats, and hamsters of both sexes, especially an overview of peripheral sensory receptors, and hormonal and central regulation. In the hormonal regulation section, we discuss potential rodent brain bisexuality, as it includes neural substrates controlling both masculine and feminine sexual preferences, i.e., masculine preference for female odors and the opposite. In the central regulation section, we show the substantial circuit regulating sexual preference and also the influence of sexual experience that innate attractants activate in the brain reward system to establish the learned attractant. Finally, we review the regulation of sexual preference by neuropeptides, oxytocin, vasopressin, and kisspeptin. Through this review, we clarified the contradictions and deficiencies in our current knowledge on the neuroendocrine regulation of sexual preference and sought to present problems requiring further study.


Assuntos
Células Quimiorreceptoras/fisiologia , Vias Neurais/fisiologia , Atrativos Sexuais/farmacologia , Comportamento Sexual Animal/fisiologia , Animais , Células Quimiorreceptoras/efeitos dos fármacos , Feminino , Masculino , Vias Neurais/efeitos dos fármacos , Comportamento Sexual Animal/efeitos dos fármacos
7.
Nat Commun ; 12(1): 4795, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34373460

RESUMO

Chemogenetic and optogenetic tools have transformed the field of neuroscience by facilitating the examination and manipulation of existing circuits. Yet, the field lacks tools that enable rational rewiring of circuits via the creation or modification of synaptic relationships. Here we report the development of HySyn, a system designed to reconnect neural circuits in vivo by reconstituting synthetic modulatory neurotransmission. We demonstrate that genetically targeted expression of the two HySyn components, a Hydra-derived neuropeptide and its receptor, creates de novo neuromodulatory transmission in a mammalian neuronal tissue culture model and functionally rewires a behavioral circuit in vivo in the nematode Caenorhabditis elegans. HySyn can interface with existing optogenetic, chemogenetic and pharmacological approaches to functionally probe synaptic transmission, dissect neuropeptide signaling, or achieve targeted modulation of specific neural circuits and behaviors.


Assuntos
Neurônios/fisiologia , Transmissão Sináptica/genética , Transmissão Sináptica/fisiologia , Animais , Comportamento Animal/fisiologia , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiologia , Cálcio , Expressão Gênica , Técnicas Genéticas , Hydra/genética , Hydra/fisiologia , Vias Neurais/fisiologia , Neuropeptídeos , Optogenética , Transdução de Sinais
8.
Nat Commun ; 12(1): 4855, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381044

RESUMO

The vertebrate brain consists of diverse neuronal types, classified by distinct anatomy and function, along with divergent transcriptomes and proteomes. Defining the cell-type specific neuroproteomes is important for understanding the development and functional organization of neural circuits. This task remains challenging in complex tissue, due to suboptimal protein isolation techniques that often result in loss of cell-type specific information and incomplete capture of subcellular compartments. Here, we develop a genetically targeted proximity labeling approach to identify cell-type specific subcellular proteomes in the mouse brain, confirmed by imaging, electron microscopy, and mass spectrometry. We virally express subcellular-localized APEX2 to map the proteome of direct and indirect pathway spiny projection neurons in the striatum. The workflow provides sufficient depth to uncover changes in the proteome of striatal neurons following chemogenetic activation of Gαq-coupled signaling cascades. This method enables flexible, cell-type specific quantitative profiling of subcellular proteome snapshots in the mouse brain.


Assuntos
Ascorbato Peroxidases/metabolismo , Núcleo Celular/metabolismo , Corpo Estriado/metabolismo , Proteoma/metabolismo , Animais , Ascorbato Peroxidases/genética , Corpo Estriado/citologia , Citosol/metabolismo , Espectrometria de Massas , Camundongos , Vias Neurais , Neurônios/citologia , Neurônios/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais , Coloração e Rotulagem , Fluxo de Trabalho
9.
Commun Biol ; 4(1): 954, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376799

RESUMO

Longitudinal menstrual cycle studies allow to investigate the effects of ovarian hormones on brain organization. Here, we use spectral dynamic causal modelling (spDCM) in a triple network model to assess effective connectivity changes along the menstrual cycle within and between the default mode, salience and executive control networks (DMN, SN, and ECN). Sixty healthy young women were scanned three times along their menstrual cycle, during early follicular, pre-ovulatory and mid-luteal phase. Related to estradiol, right before ovulation the left insula recruits the ECN, while the right middle frontal gyrus decreases its connectivity to the precuneus and the DMN decouples into anterior/posterior parts. Related to progesterone during the mid-luteal phase, the insulae (SN) engage to each other, while decreasing their connectivity to parietal ECN, which in turn engages the posterior DMN. When including the most confident connections in a leave-one out cross-validation, we find an above-chance prediction of the left-out subjects' cycle phase. These findings corroborate the plasticity of the female brain in response to acute hormone fluctuations and may help to further understand the neuroendocrine interactions underlying cognitive changes along the menstrual cycle.


Assuntos
Estradiol/metabolismo , Ciclo Menstrual/fisiologia , Vias Neurais/fisiologia , Progesterona/metabolismo , Adulto , Mapeamento Encefálico , Feminino , Humanos , Adulto Jovem
10.
Neuroimage Clin ; 31: 102774, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34371239

RESUMO

BACKGROUND: The complex crossing-fiber characteristics in the dual-stream system have been ignored by traditional diffusion tensor models regarding disconnections in post-stroke aphasia. It is valuable to identify microstructural damage of crossing-fiber pathways and reveal accurate fiber-specific language mapping in patients with aphasia. METHODS: This cross-sectional study collected magnetic resonance imaging data from 29 participants with post-stroke aphasia in the subacute stage and from 33 age- and sex-matched healthy controls. Fixel-based analysis was performed to examine microstructural fiber density (FD) and bundle cross-section alterations of specific fiber populations in crossing-fiber regions. Group comparisons were performed, and relationships with language scores were assessed. RESULTS: The aphasic group exhibited significant fixel-wise FD reductions in the dual-stream tracts, including the left inferior fronto-occipital fasciculus (IFOF), arcuate fasciculus, and superior longitudinal fasciculus (SLF) III (family-wise-error-corrected p < 0.05). Voxel- and fixel-wise comparisons revealed mismatched distributions in regions with crossing-fiber nexuses. Fixel-wise correlation analyses revealed significant associations between comprehension impairment and reduced FD in the temporal and frontal segments of the left IFOF, and also mapped naming ability to the IFOF. Average features along the whole course of dominant tracts assessed with tract-wise analyses attributed word-level comprehension to the IFOF (r = 0.723, p < 0.001) and revealed a trend-level correlation between sentence-level comprehension and FD of the SLF III (r = 0.451, p = 0.021). The mean FD of the uncinate fasciculus (UF) and IFOF correlated with total and picture naming scores, and the IFOF also correlated with responsive naming subdomains (Bonferroni corrected p < 0.05). CONCLUSIONS: FD reductions of dual streams suggest that intra-axonal volume reduction constitutes the microstructural damage of white matter integrity in post-stroke aphasia. Fixel-based analysis provides a complementary method of language mapping that identifies fiber-specific tracts in the left hemisphere language network with greater specificity than voxel-based analysis. It precisely locates the precise segments of the IFOF for comprehension, yields fiber-specific evidence for the debated UF-naming association, and reveals dissociative subdomain associations with distinct tracts.


Assuntos
Afasia , Acidente Vascular Cerebral , Substância Branca , Afasia/diagnóstico por imagem , Afasia/etiologia , Estudos Transversais , Imagem de Tensor de Difusão , Humanos , Idioma , Vias Neurais/diagnóstico por imagem , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Substância Branca/diagnóstico por imagem
11.
Medicine (Baltimore) ; 100(31): e26840, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397854

RESUMO

RATIONALE: We report on a patient whose arcuate fasciculus (AF) and corticobulbar tract (CBT) recovered following an infarct in the middle cerebral artery (MCA) territory, demonstrated on serial diffusion tensor tractography (DTT). PATIENT CONCERNS: The patient showed moderate conduction aphasia on the Western Aphasia Battery with an aphasia quotient of 46.5‰ (spontaneous speech: 35.0‰, auditory comprehension: 36.0‰, and naming: 53.1‰) at 1 month after onset. His aphasia improved with an aphasia quotient of 49‰ (spontaneous speech: 71.0‰, auditory comprehension: 52.0‰, and naming: 59.0‰) at 10 months after onset. DIAGNOSIS: A 44-year-old right-handed male patient presented with aphasia and quadriplegia, which occurred at the onset of an infarct in the left MCA territory. INTERVENTION: Diffusion tensor imaging data were acquired twice (1 month and 10 months after onset). OUTCOMES: On one-month DTT, the discontinuation of the left AF and severe narrowing of the right CBT were observed. However, on ten-month DTT, the left AF was connected to the opposite AF by a new tract that passed through the splenium of corpus callosum, and the right CBT had become thicker. LESSONS: We believe that our results suggest a recovery mechanism of injured AF and CBT in stroke patients.


Assuntos
Afasia , Encéfalo , Área de Broca , Infarto da Artéria Cerebral Média , Área de Wernicke , Adulto , Afasia/diagnóstico , Afasia/etiologia , Afasia/reabilitação , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Humanos , Infarto da Artéria Cerebral Média/diagnóstico , Infarto da Artéria Cerebral Média/fisiopatologia , Infarto da Artéria Cerebral Média/reabilitação , Masculino , Vias Neurais/patologia , Vias Neurais/fisiopatologia , Reabilitação Neurológica/métodos , Tratos Piramidais/patologia , Recuperação de Função Fisiológica , Fonoterapia/métodos , Resultado do Tratamento
12.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(3): 230-234, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34374232

RESUMO

Objective: To investigate the obestatin neural projections from arcuate nucleus (ARC) to hippocampus in diabetic rats, and its effects on gastric motility and gastric emptying of rats. Methods: Diabetic model was established by fructose intake combined with streptozotocin injected intraperitoneally in healthy male Wistar rats. Diabetic rats were randomly divided into five groups: control group (NS group), 0.1, 1 and 10 pmol obestatin group, and obestatin + NBI27914 group, with 7 rats in each group. 0.5 µl saline (NS), obestatin (0.1 pmol, 1 pmol, 10 pmol) or the mixture (10 pmol obestatin + 60 pmol NBI27914) was injected into the hippocampus respectively, the gastric motility was recorded immediately after administration, and the gastric emptying was studied 15 min later. ARC-hippocampus obestatin neural pathway and ARC obestatin mRNA expression were compared between normal and diabetic rats with fluorogold (FG) retrograde tracing and immunofluorescence histochemical staining. Results: Compared with normal rats, the number of ARC FG/obestatin double labeled neurons and the expression level of ARC obestatin mRNA were decreased significantly in diabetic rats (P<0.05); Obestatin could inhibit gastric motility and gastric emptying in a dose-dependent manner (P<0.05~0.01) and the effects of obestatin could be partially blocked by NBI27914, an antagonist of corticotropin releasing factor receptor 1 (CRFR1) (P<0.05). Compared with normal rats, the inhibitory effects of obestatin on gastric motility and gastric emptying were significantly decreased in diabetic rats (P<0.05). Conclusion: There is an obestatin neural pathway between ARC and hippocampus, which participates in the regulation of gastric motility and gastric emptying in diabetic rats, and CRFR1 signal pathway is involved in this process. The damage of this neural pathway may participate in gastric motility dysfunction in early stage of diabetes.


Assuntos
Diabetes Mellitus Experimental , Grelina , Animais , Esvaziamento Gástrico , Motilidade Gastrointestinal , Hipocampo , Masculino , Vias Neurais , Ratos , Ratos Wistar
13.
Brain Behav ; 11(8): e2314, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34333874

RESUMO

INTRODUCTION: Cognitive impairment is common in hemodialysis (HD) patients; however, the underlying mechanisms have not been fully understood. The "triple-network model" that consists of the salience network (SN), central executive network (CEN), and default mode network (DMN) has been suggested to play an important role in various cognitive functions. However, dynamic functional connectivity (FC) alterations within the triple networks have not been investigated in HD patients. METHODS: Sixty-six HD patients and 66 healthy controls (HCs) were included in this study. The triple networks were identified using a group spatial independent component analysis, and dynamic FC was analyzed using a sliding window approach and k-means clustering algorithm. Furthermore, we analyzed the relationships between altered dynamic FC parameters and clinical variables in HD patients. RESULTS: The intrinsic brain FC within the triple networks was clustered into four configuration states. Compared with HCs, HD patients spent more time in State 1, which was characterized by weak connections between the DMN and CEN and SN. HD patients showed lower number of transitions across different states than HCs. Moreover, the number of transitions and mean dwell time in State 1 were associated with cognitive performance in HD patients. CONCLUSION: Our findings suggest abnormal dynamic FC properties within the triple networks in HD patients, which may provide new insights into the pathophysiological mechanisms of their cognitive deficits from the perspective of dynamic FC.


Assuntos
Disfunção Cognitiva , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Disfunção Cognitiva/etiologia , Humanos , Vias Neurais/diagnóstico por imagem , Diálise Renal
14.
Am J Psychiatry ; 178(10): 952-964, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34407624

RESUMO

OBJECTIVE: Neural activations during auditory oddball tasks may be endophenotypes for psychosis and bipolar disorder. The authors investigated oddball neural deviations that discriminate multiple diagnostic groups across the schizophrenia-bipolar spectrum (schizophrenia, schizoaffective disorder, psychotic bipolar disorder, and nonpsychotic bipolar disorder) and clarified their relationship to clinical and cognitive features. METHODS: Auditory oddball responses to standard and target tones from 64 sensor EEG recordings were compared across patients with psychosis (total N=597; schizophrenia, N=225; schizoaffective disorder, N=201; bipolar disorder with psychosis, N=171), patients with bipolar disorder without psychosis (N=66), and healthy comparison subjects (N=415) from the second iteration of the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP2) study. EEG activity was analyzed in voltage and in the time-frequency domain (low, beta, and gamma bands). Event-related potentials (ERPs) were compared with those from an independent sample collected during the first iteration of B-SNIP (B-SNIP1; healthy subjects, N=211; psychosis group, N=526) to establish the repeatability of complex oddball ERPs across multiple psychosis syndromes (r values >0.94 between B-SNIP1 and B-SNIP2). RESULTS: Twenty-six EEG features differentiated the groups; they were used in discriminant and correlational analyses. EEG variables from the N100, P300, and low-frequency ranges separated the groups along a diagnostic continuum from healthy to bipolar disorder with psychosis/bipolar disorder without psychosis to schizoaffective disorder/schizophrenia and were strongly related to general cognitive function (r=0.91). P50 responses to standard trials and early beta/gamma frequency responses separated the bipolar disorder without psychosis group from the bipolar disorder with psychosis group. P200, N200, and late beta/gamma frequency responses separated the two bipolar disorder groups from the other groups. CONCLUSIONS: Neural deviations during auditory processing are related to psychosis history and bipolar disorder. There is a powerful transdiagnostic relationship between severity of these neural deviations and general cognitive performance. These results have implications for understanding the neurobiology of clinical syndromes across the schizophrenia-bipolar spectrum that may have an impact on future biomarker research.


Assuntos
Vias Auditivas/fisiopatologia , Transtorno Bipolar , Eletroencefalografia/métodos , Vias Neurais/fisiopatologia , Transtornos Psicóticos , Estimulação Acústica/métodos , Adulto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Cognição , Correlação de Dados , Diagnóstico Diferencial , Potenciais Evocados Auditivos , Feminino , Humanos , Masculino , Técnicas Psicológicas , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/fisiopatologia , Transtornos Psicóticos/psicologia , Índice de Gravidade de Doença
15.
Elife ; 102021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34372969

RESUMO

Brain injuries can interrupt descending neural pathways that convey motor commands from the cortex to spinal motoneurons. Here, we demonstrate that a unilateral injury of the hindlimb sensorimotor cortex of rats with completely transected thoracic spinal cord produces hindlimb postural asymmetry with contralateral flexion and asymmetric hindlimb withdrawal reflexes within 3 hr, as well as asymmetry in gene expression patterns in the lumbar spinal cord. The injury-induced postural effects were abolished by hypophysectomy and were mimicked by transfusion of serum from animals with brain injury. Administration of the pituitary neurohormones ß-endorphin or Arg-vasopressin-induced side-specific hindlimb responses in naive animals, while antagonists of the opioid and vasopressin receptors blocked hindlimb postural asymmetry in rats with brain injury. Thus, in addition to the well-established involvement of motor pathways descending from the brain to spinal circuits, the side-specific humoral signaling may also add to postural and reflex asymmetries seen after brain injury.


Assuntos
Lesões Encefálicas/fisiopatologia , Vias Neurais/fisiologia , Reflexo , Córtex Sensório-Motor/fisiologia , Animais , Lesões Encefálicas/metabolismo , Masculino , Vias Neurais/metabolismo , Ratos , Ratos Sprague-Dawley , Ratos Wistar
16.
Nat Neurosci ; 24(10): 1402-1413, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34373644

RESUMO

Pain decreases the activity of many ventral tegmental area (VTA) dopamine (DA) neurons, yet the underlying neural circuitry connecting nociception and the DA system is not understood. Here we show that a subpopulation of lateral parabrachial (LPB) neurons is critical for relaying nociceptive signals from the spinal cord to the substantia nigra pars reticulata (SNR). SNR-projecting LPB neurons are activated by noxious stimuli and silencing them blocks pain responses in two different models of pain. LPB-targeted and nociception-recipient SNR neurons regulate VTA DA activity directly through feed-forward inhibition and indirectly by inhibiting a distinct subpopulation of VTA-projecting LPB neurons thereby reducing excitatory drive onto VTA DA neurons. Correspondingly, ablation of SNR-projecting LPB neurons is sufficient to reduce pain-mediated inhibition of DA release in vivo. The identification of a neural circuit conveying nociceptive input to DA neurons is critical to our understanding of how pain influences learning and behavior.


Assuntos
Neurônios Dopaminérgicos , Mesencéfalo/fisiopatologia , Vias Neurais/fisiopatologia , Dor/fisiopatologia , Núcleos Parabraquiais/fisiopatologia , Medula Espinal/fisiopatologia , Animais , Comportamento Animal , Mapeamento Encefálico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios , Nociceptividade , Optogenética , Dor/psicologia , Manejo da Dor , Substância Negra/fisiopatologia , Área Tegmentar Ventral/fisiopatologia
17.
Nature ; 596(7871): 257-261, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34349261

RESUMO

An animal's nervous system changes as its body grows from birth to adulthood and its behaviours mature1-8. The form and extent of circuit remodelling across the connectome is unknown3,9-15. Here we used serial-section electron microscopy to reconstruct the full brain of eight isogenic Caenorhabditis elegans individuals across postnatal stages to investigate how it changes with age. The overall geometry of the brain is preserved from birth to adulthood, but substantial changes in chemical synaptic connectivity emerge on this consistent scaffold. Comparing connectomes between individuals reveals substantial differences in connectivity that make each brain partly unique. Comparing connectomes across maturation reveals consistent wiring changes between different neurons. These changes alter the strength of existing connections and create new connections. Collective changes in the network alter information processing. During development, the central decision-making circuitry is maintained, whereas sensory and motor pathways substantially remodel. With age, the brain becomes progressively more feedforward and discernibly modular. Thus developmental connectomics reveals principles that underlie brain maturation.


Assuntos
Encéfalo/citologia , Encéfalo/crescimento & desenvolvimento , Caenorhabditis elegans/citologia , Conectoma , Modelos Neurológicos , Vias Neurais , Sinapses/fisiologia , Envelhecimento/metabolismo , Animais , Encéfalo/anatomia & histologia , Encéfalo/ultraestrutura , Caenorhabditis elegans/anatomia & histologia , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/ultraestrutura , Individualidade , Interneurônios/citologia , Microscopia Eletrônica , Neurônios/citologia , Comportamento Estereotipado
18.
Elife ; 102021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34397382

RESUMO

The claustrum is a functionally and structurally complex brain region, whose very spatial extent remains debated. Histochemical-based approaches typically treat the claustrum as a relatively narrow anatomical region that primarily projects to the neocortex, whereas circuit-based approaches can suggest a broader claustrum region containing projections to the neocortex and other regions. Here, in the mouse, we took a bottom-up and cell-type-specific approach to complement and possibly unite these seemingly disparate conclusions. Using single-cell RNA-sequencing, we found that the claustrum comprises two excitatory neuron subtypes that are differentiable from the surrounding cortex. Multicolor retrograde tracing in conjunction with 12-channel multiplexed in situ hybridization revealed a core-shell spatial arrangement of these subtypes, as well as differential downstream targets. Thus, the claustrum comprises excitatory neuron subtypes with distinct molecular and projection properties, whose spatial patterns reflect the narrower and broader claustral extents debated in previous research. This subtype-specific heterogeneity likely shapes the functional complexity of the claustrum.


Assuntos
Claustrum/anatomia & histologia , Vias Neurais/anatomia & histologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/citologia , Análise de Sequência de RNA , Análise de Célula Única
19.
Nat Commun ; 12(1): 4788, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34373454

RESUMO

Activity in numerous brain regions drives heroin seeking, but no circuits that limit heroin seeking have been identified. Furthermore, the neural circuits controlling opioid choice are unknown. In this study, we examined the role of the infralimbic cortex (IL) to nucleus accumbens shell (NAshell) pathway during heroin choice and relapse. This model yielded subpopulations of heroin versus food preferring rats during choice, and choice was unrelated to subsequent relapse rates to heroin versus food cues, suggesting that choice and relapse are distinct behavioral constructs. Supporting this, inactivation of the IL with muscimol produced differential effects on opioid choice versus relapse. A pathway-specific chemogenetic approach revealed, however, that the IL-NAshell pathway acts as a common limiter of opioid choice and relapse. Furthermore, dendritic spines in IL-NAshell neurons encode distinct aspects of heroin versus food reinforcement. Thus, opioid choice and relapse share a common addiction-limiting circuit in the IL-NAshell pathway.


Assuntos
Analgésicos Opioides/farmacologia , Comportamento Aditivo , Comportamento de Procura de Droga/efeitos dos fármacos , Transtornos Relacionados ao Uso de Opioides , Animais , Comportamento Animal , Encéfalo/patologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/fisiologia , Sinais (Psicologia) , Tomada de Decisões/efeitos dos fármacos , Ingestão de Alimentos/psicologia , Extinção Psicológica/fisiologia , Alimentos , Heroína/farmacologia , Dependência de Heroína , Masculino , Vias Neurais/fisiologia , Núcleo Accumbens/metabolismo , Ratos , Recidiva , Reforço Psicológico , Roedores , Autoadministração
20.
Nature ; 597(7876): 410-414, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34408322

RESUMO

Signals from sympathetic neurons and immune cells regulate adipocytes and thereby contribute to fat tissue biology. Interactions between the nervous and immune systems have recently emerged as important regulators of host defence and inflammation1-4. Nevertheless, it is unclear whether neuronal and immune cells co-operate in brain-body axes to orchestrate metabolism and obesity. Here we describe a neuro-mesenchymal unit that controls group 2 innate lymphoid cells (ILC2s), adipose tissue physiology, metabolism and obesity via a brain-adipose circuit. We found that sympathetic nerve terminals act on neighbouring adipose mesenchymal cells via the ß2-adrenergic receptor to control the expression of glial-derived neurotrophic factor (GDNF) and the activity of ILC2s in gonadal fat. Accordingly, ILC2-autonomous manipulation of the GDNF receptor machinery led to alterations in ILC2 function, energy expenditure, insulin resistance and propensity to obesity. Retrograde tracing and chemical, surgical and chemogenetic manipulations identified a sympathetic aorticorenal circuit that modulates ILC2s in gonadal fat and connects to higher-order brain areas, including the paraventricular nucleus of the hypothalamus. Our results identify a neuro-mesenchymal unit that translates cues from long-range neuronal circuitry into adipose-resident ILC2 function, thereby shaping host metabolism and obesity.


Assuntos
Tecido Adiposo/inervação , Tecido Adiposo/metabolismo , Encéfalo/metabolismo , Imunidade Inata/imunologia , Mesoderma/citologia , Vias Neurais , Neurônios/citologia , Obesidade/metabolismo , Tecido Adiposo/citologia , Animais , Encéfalo/citologia , Sinais (Psicologia) , Citocinas/metabolismo , Metabolismo Energético , Feminino , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Gônadas/metabolismo , Mesoderma/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Proteínas Proto-Oncogênicas c-ret/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Sistema Nervoso Simpático/citologia , Sistema Nervoso Simpático/metabolismo
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