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1.
Neurosurgery ; 91(3): 485-495, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35876672

RESUMO

BACKGROUND: Arteriovenous malformations (AVMs) of the diencephalon (DC) and brainstem (BS) are difficult to treat. Stereotactic radiosurgery (SRS) is a reasonable option; however, an optimal radiosurgical dose needs to be established to optimize long-term outcomes. OBJECTIVE: To evaluate dose-dependent long-term outcomes of SRS for DC/BS-AVMs. METHODS: We retrospectively analyzed the long-term outcomes of 118 patients who had SRS-treated DC/BS-AVMs. The outcomes included post-SRS hemorrhage, AVM obliteration, neurological outcomes, and disease-specific survival. According to margin doses, the patients were classified into low (<18 Gy), medium (18-20 Gy), and high (>20 Gy) dose groups. RESULTS: SRS reduced the annual hemorrhage rate from 8.6% to 1.6% before obliteration and 0.0% after obliteration. The cumulative hemorrhage rate in the low dose group was likely to be higher than that in the other groups ( P = .113). The cumulative obliteration rates in the entire cohort were 74% and 83% at 5 and 10 years, respectively, and were significantly lower in the low dose group than in the other groups (vs medium dose: P = .027, vs high dose: P = .016). Multivariate analyses demonstrated that low dose SRS was significantly associated with worse obliteration rates (hazard ratio 0.18, 95% CI 0.04-0.79; P = .023). CONCLUSION: SRS with a margin dose of 18 to 20 Gy for DC/BS-AVMs may be optimal, providing a higher obliteration rate and lower risk of post-SRS hemorrhage than lower dose SRS. Dose reduction to <18 Gy should only be optional when higher doses are intolerable.


Assuntos
Malformações Arteriovenosas Intracranianas , Radiocirurgia , Tronco Encefálico , Diencéfalo , Seguimentos , Humanos , Malformações Arteriovenosas Intracranianas/etiologia , Malformações Arteriovenosas Intracranianas/radioterapia , Malformações Arteriovenosas Intracranianas/cirurgia , Margens de Excisão , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
2.
J Comp Neurol ; 530(14): 2537-2561, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35708548

RESUMO

Many transcription factors boost neural development and differentiation in specific directions and serve for identifying similar or homologous structures across species. The expression of Orthopedia (Otp) is critical for the development of certain cell groups along the vertebrate neuraxis, for example, the medial amygdala or hypothalamic neurosecretory neurons. Therefore, the primary focus of the present study is the distribution of Orthopedia a (Otpa) in the larval and adult zebrafish (Danio rerio) brain. Since Otpa is also critical for the development of zebrafish basal diencephalic dopaminergic cells, colocalization of Otpa with the catecholamine synthesizing enzyme tyrosine hydroxylase (TH) is studied. Cellular colocalization of Otpa and dopamine is only seen in magnocellular neurons of the periventricular posterior tubercular nucleus and in the posterior tuberal nucleus. Otpa-positive cells occur in many additional structures along the zebrafish neuraxis, from the secondary prosencephalon down to the hindbrain. Furthermore, Otpa expression is studied in shh-GFP and islet1-GFP transgenic zebrafish. Otpa-positive cells only express shh in dopaminergic magnocellular periventricular posterior tubercular cells, and only colocalize with islet1-GFP in the ventral zone and prerecess caudal periventricular hypothalamic zone and the perilemniscal nucleus. The scarcity of cellular colocalization of Otpa in islet1-GFP cells indicates that the Shh-islet1 neurogenetic pathway is not active in most Otpa-expressing domains. Our analysis reveals detailed correspondences between mouse and zebrafish forebrain territories including the zebrafish intermediate nucleus of the ventral telencephalon and the mouse medial amygdala. The zebrafish preoptic Otpa-positive domain represents the neuropeptidergic supraopto-paraventricular region of all tetrapods. Otpa domains in the zebrafish basal plate hypothalamus suggest that the ventral periventricular hypothalamic zone corresponds to the otp-expressing basal hypothalamic tuberal field in the mouse. Furthermore, the mouse otp domain in the mammillary hypothalamus compares partly to our Otpa-positive domain in the prerecess caudal periventricular hypothalamic zone (Hc-a).


Assuntos
Dopamina , Peixe-Zebra , Animais , Encéfalo/metabolismo , Diencéfalo/metabolismo , Dopamina/metabolismo , Camundongos , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
3.
eNeuro ; 9(2)2022.
Artigo em Inglês | MEDLINE | ID: mdl-35365502

RESUMO

Single-brain neuroimaging studies have shown that human cooperation is associated with neural activity in frontal and temporoparietal regions. However, it remains unclear whether single-brain studies are informative about cooperation in real life, where people interact dynamically. Such dynamic interactions have become the focus of interbrain studies. An advantageous technique in this regard is functional near-infrared spectroscopy (fNIRS) because it is less susceptible to movement artifacts than more conventional techniques like electroencephalography (EEG) or functional magnetic resonance imaging (fMRI). We conducted a systematic review and the first quantitative meta-analysis of fNIRS hyperscanning of cooperation, based on thirteen studies with 890 human participants. Overall, the meta-analysis revealed evidence of statistically significant interbrain synchrony while people were cooperating, with large overall effect sizes in both frontal and temporoparietal areas. All thirteen studies observed significant interbrain synchrony in the prefrontal cortex (PFC), suggesting that this region is particularly relevant for cooperative behavior. The consistency in these findings is unlikely to be because of task-related activations, given that the relevant studies used diverse cooperation tasks. Together, the present findings support the importance of interbrain synchronization of frontal and temporoparietal regions in interpersonal cooperation. Moreover, the present article highlights the usefulness of meta-analyses as a tool for discerning patterns in interbrain dynamics.


Assuntos
Mapeamento Encefálico , Comportamento Cooperativo , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Diencéfalo , Humanos , Córtex Pré-Frontal/diagnóstico por imagem , Espectroscopia de Luz Próxima ao Infravermelho/métodos
4.
Trends Neurosci ; 45(5): 346-357, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35236639

RESUMO

In recent years the study of dynamic, between-brain coupling mechanisms has taken social neuroscience by storm. In particular, interbrain synchrony (IBS) is a putative neural mechanism said to promote social interactions by enabling the functional integration of multiple brains. In this article, I argue that this research is beset with three pervasive and interrelated problems. First, the field lacks a widely accepted definition of IBS. Second, IBS wants for theories that can guide the design and interpretation of experiments. Third, a potpourri of tasks and empirical methods permits undue flexibility when testing the hypothesis. These factors synergistically undermine IBS as a theoretical construct. I finish by recommending measures that can address these issues.


Assuntos
Síndrome do Intestino Irritável , Encéfalo , Mapeamento Encefálico/métodos , Diencéfalo , Eletroencefalografia/métodos , Humanos
5.
Dev Neurorehabil ; 25(6): 426-432, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35341463

RESUMO

Shared emotional experiences during musical activities among musicians can be coupled with brainwave synchronization. For non-speaking individuals with CP, verbal communication may be limited in expressing mutual empathy. Therefore, this case study explored interbrain synchronization among a non-speaking CP (female, 18 yrs), her parent, and a music therapist by measuring their brainwaves simultaneously during four music and four storytelling sessions. In only the youth-parent dyad, we observed a significantly higher level of interbrain synchronization during music rather than story-telling condition. However, in both the youth-parent and youth-therapist dyad, regardless of condition type, significant interbrain synchronization emerged in frontal and temporal lobes in the low-frequency bands, which are associated with socio-emotional responses. Although interbrain synchronization may have been induced by multiple factors (e.g., external stimuli, shared empathetic experiences, and internal physiological rhythms), the music activity setting deserves further study as a potential facilitator of neurophysiological synchrony between youth with CP and caregivers/healthcare providers.


Assuntos
Paralisia Cerebral , Música , Adolescente , Encéfalo , Diencéfalo , Eletroencefalografia , Feminino , Humanos , Pais
7.
Cereb Cortex ; 32(18): 4110-4127, 2022 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-35029645

RESUMO

When people interact with each other, their brains synchronize. However, it remains unclear whether interbrain synchrony (IBS) is functionally relevant for social interaction or stems from exposure of individual brains to identical sensorimotor information. To disentangle these views, the current dual-EEG study investigated amplitude-based IBS in pianists jointly performing duets containing a silent pause followed by a tempo change. First, we manipulated the similarity of the anticipated tempo change and measured IBS during the pause, hence, capturing the alignment of purely endogenous, temporal plans without sound or movement. Notably, right posterior gamma IBS was higher when partners planned similar tempi, it predicted whether partners' tempi matched after the pause, and it was modulated only in real, not in surrogate pairs. Second, we manipulated the familiarity with the partner's actions and measured IBS during joint performance with sound. Although sensorimotor information was similar across conditions, gamma IBS was higher when partners were unfamiliar with each other's part and had to attend more closely to the sound of the performance. These combined findings demonstrate that IBS is not merely an epiphenomenon of shared sensorimotor information but can also hinge on endogenous, cognitive processes crucial for behavioral synchrony and successful social interaction.


Assuntos
Síndrome do Intestino Irritável , Encéfalo , Mapeamento Encefálico , Diencéfalo , Humanos , Movimento
8.
J Comp Neurol ; 530(10): 1569-1587, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35015905

RESUMO

We studied the expression of neurogranin in the brain and some sensory organs (barbel taste buds, olfactory organs, and retina) of adult zebrafish. Database analysis shows zebrafish has two paralog neurogranin genes (nrgna and nrgnb) that translate into three peptides with a conserved IQ domain, as in mammals. Western blots of zebrafish brain extracts using an anti-neurogranin antiserum revealed three separate bands, confirming the presence of three neurogranin peptides. Immunohistochemistry shows neurogranin-like expression in the brain and sensory organs (taste buds, neuromasts and olfactory epithelium), not being able to discern its three different peptides. In the retina, the most conspicuous positive cells were bipolar neurons. In the brain, immunopositive neurons were observed in all major regions (pallium, subpallium, preoptic area, hypothalamus, diencephalon, mesencephalon and rhombencephalon, including the cerebellum), a more extended distribution than in mammals. Interestingly, dendrites, cell bodies and axon terminals of some neurons were immunopositive, thus zebrafish neurogranins may play presynaptic and postsynaptic roles. Most positive neurons were found in primary sensory centers (viscerosensory column and medial octavolateral nucleus) and integrative centers (pallium, subpallium, optic tectum and cerebellum), which have complex synaptic circuitry. However, we also observed expression in areas not related to sensory or integrative functions, such as in cerebrospinal fluid-contacting cells associated with the hypothalamic recesses, which exhibited high neurogranin-like immunoreactivity. Together, these results reveal important differences with the patterns reported in mammals, suggesting divergent evolution from the common ancestor.


Assuntos
Neurogranina , Peixe-Zebra , Animais , Encéfalo/metabolismo , Diencéfalo/metabolismo , Mamíferos , Neurogranina/análise , Neurogranina/metabolismo , Rombencéfalo/química , Peixe-Zebra/metabolismo
9.
Environ Sci Pollut Res Int ; 29(1): 936-948, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34345985

RESUMO

Fipronil (FIP) is a highly effective insecticide that has been used in agriculture and veterinary medicine. Its neurotoxic effect to insects and to non-target organisms, after nonintentional exposure, was reported. Many studies were conducted to evaluate FIP effects on mammals. However, slight is known about its effect on the brain stem and diencephalon. The current study was designed to investigate the ability of FIP to induce oxidative stress as a molecular mechanism of FIP neurotoxicity that resulted in apoptosis and neural tissue reactivity in these regions. Ten adult male rats received 10 mg/kg of FIP technical grade by oral gavage, daily for 45 days. Brain stem and diencephalon were processed to examine oxidative stress-induced macromolecular alteration (MDA, PCC and DNA fragmentation). Also, the histopathological assessment and immunoreactivity for caspase-3 (active form), iNOS and GFAP were performed on the thalamus, hypothalamus and medulla oblongata. Our results revealed that FIP significantly raised MDA, PCC and DNA fragmentation (p ≤ 0.05). In addition, significantly increased immunoreactivity to GFAP, iNOS and caspase-3 (active form) in the FIP-treated group was noticed (p ≤ 0.05). Moreover, alterations in the histoarchitecture of the neural tissue of these regions were observed. We conclude that FIP can induce oxidative stress, leading to apoptosis and tissue reaction in brain stem and diencephalon.


Assuntos
Apoptose , Tronco Encefálico/patologia , Diencéfalo/patologia , Estresse Oxidativo , Pirazóis/toxicidade , Animais , Apoptose/efeitos dos fármacos , Tronco Encefálico/efeitos dos fármacos , Diencéfalo/efeitos dos fármacos , Inseticidas/toxicidade , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos
10.
Ann N Y Acad Sci ; 1508(1): 178-195, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34750828

RESUMO

How musical emotions and the pleasure derived from music, regardless of the musical valence, can be shared between individuals is a fascinating question, and investigating it can shed light on the function of musical reward. We carried out our investigations in a natural setting during an international competition for orchestra conductors. Participants (n = 15) used a dedicated smartphone app to report their subjective emotional experiences in real time while we recorded their cerebral activity using electroencephalography and their electrodermal activity. The overall behavioral real-time behavioral ratings suggest a possible social influence on the reported and felt pleasure. The physically closer the participants, the more similar their reported pleasure. By calculating the interindividual cerebral coherence (n = 21 pairs), we showed that when people simultaneously reported either high or low pleasure, their cerebral activities were closer than for simultaneous neutral pleasure reports. Participants' skin conductance levels were also more coupled when reporting higher emotional degrees simultaneously. More importantly, the participants who were physically closer had higher cerebral coherence, but only when they simultaneously reported a high level of pleasure. We propose that emotional contagion and/or emotional resonance mechanisms could explain why a form of "emotional connecting force" arises between people during shared appraisal situations.


Assuntos
Percepção Auditiva/fisiologia , Diencéfalo/fisiologia , Eletroencefalografia , Música , Prazer , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
Science ; 374(6566): eaba9584, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34672724

RESUMO

Social interactions occur in group settings and are mediated by communication signals that are exchanged between individuals, often using vocalizations. The neural representation of group social communication remains largely unexplored. We conducted simultaneous wireless electrophysiological recordings from the frontal cortices of groups of Egyptian fruit bats engaged in both spontaneous and task-induced vocal interactions. We found that the activity of single neurons distinguished between vocalizations produced by self and by others, as well as among specific individuals. Coordinated neural activity among group members exhibited stable bidirectional interbrain correlation patterns specific to spontaneous communicative interactions. Tracking social and spatial arrangements within a group revealed a relationship between social preferences and intra- and interbrain activity patterns. Combined, these findings reveal a dedicated neural repertoire for group social communication within and across the brains of freely communicating groups of bats.


Assuntos
Quirópteros/fisiologia , Ecolocação , Lobo Frontal/fisiologia , Comportamento Social , Vocalização Animal , Animais , Quirópteros/psicologia , Diencéfalo/fisiologia , Feminino , Masculino , Interação Social
12.
eNeuro ; 8(5)2021.
Artigo em Inglês | MEDLINE | ID: mdl-34607804

RESUMO

Team flow occurs when a group functions in a high task engagement to achieve a goal, commonly seen in performance and sports. Team flow can enable enhanced positive experiences, as compared with individual flow or regular socializing. However, the neural basis for this enhanced behavioral state remains unclear. Here, we identified neural correlates (NCs) of team flow in human participants using a music rhythm task with electroencephalogram hyperscanning. Experimental manipulations held the motor task constant while disrupting the corresponding hedonic music to interfere with the flow state or occluding the partner's positive feedback to impede team interaction. We validated these manipulations by using psychometric ratings and an objective measure for the depth of flow experience, which uses the auditory-evoked potential (AEP) of a task-irrelevant stimulus. Spectral power analysis at both the scalp sensors and anatomic source levels revealed higher ß-γ power specific to team flow in the left middle temporal cortex (L-MTC). Causal interaction analysis revealed that the L-MTC is downstream in information processing and receives information from areas encoding the flow or social states. The L-MTC significantly contributes to integrating information. Moreover, we found that team flow enhances global interbrain integrated information (II) and neural synchrony. We conclude that the NCs of team flow induce a distinct brain state. Our results suggest a neurocognitive mechanism to create this unique experience.


Assuntos
Encéfalo , Música , Cognição , Diencéfalo , Eletroencefalografia , Humanos
13.
EMBO J ; 40(21): e107532, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34549820

RESUMO

Astrocytes regulate brain-wide functions and also show region-specific differences, but little is known about how general and region-specific functions are aligned at the single-cell level. To explore this, we isolated adult mouse diencephalic astrocytes by ACSA-2-mediated magnetic-activated cell sorting (MACS). Single-cell RNA-seq revealed 7 gene expression clusters of astrocytes, with 4 forming a supercluster. Within the supercluster, cells differed by gene expression related to ion homeostasis or metabolism, with the former sharing gene expression with other regions and the latter being restricted to specific regions. All clusters showed expression of proliferation-related genes, and proliferation of diencephalic astrocytes was confirmed by immunostaining. Clonal analysis demonstrated low level of astrogenesis in the adult diencephalon, but not in cerebral cortex grey matter. This led to the identification of Smad4 as a key regulator of diencephalic astrocyte in vivo proliferation and in vitro neurosphere formation. Thus, astrocytes show diverse gene expression states related to distinct functions with some subsets being more widespread while others are more regionally restricted. However, all share low-level proliferation revealing the novel concept of adult astrogenesis in the diencephalon.


Assuntos
Astrócitos/metabolismo , Linhagem da Célula/genética , Diencéfalo/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Neurogênese/genética , Proteína Smad4/genética , Animais , Astrócitos/classificação , Astrócitos/citologia , Ciclo Celular/genética , Diferenciação Celular , Proliferação de Células , Córtex Cerebral/citologia , Córtex Cerebral/crescimento & desenvolvimento , Córtex Cerebral/metabolismo , Diencéfalo/citologia , Diencéfalo/crescimento & desenvolvimento , Ontologia Genética , Redes Reguladoras de Genes , Substância Cinzenta/citologia , Substância Cinzenta/crescimento & desenvolvimento , Substância Cinzenta/metabolismo , Redes e Vias Metabólicas , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Anotação de Sequência Molecular , Família Multigênica , Transdução de Sinais , Proteína Smad4/metabolismo
14.
Folia Histochem Cytobiol ; 59(3): 145-156, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34309826

RESUMO

INTRODUCTION: A recent study has shown a close neuroanatomical relationship between the enkephalinergic (methionine-enkephalin) and tachykininergic (substance P) systems in the alpaca diencephalon. In this study, our aim is to show this relationship in the alpaca brainstem. MATERIAL AND METHODS: Using an immunohistochemical technique, the distribution of immunoreactive (Ir) fibers and cell bodies containing substance P (SP) or methionine-enkephalin (MET) has been studied in the alpaca brainstem. Five adult males were used; brain tissue was fixed and processed by standard methods. RESULTS: SP- and MET-Ir fibers showed a widespread and similar distribution in the mesencephalon, pons and medulla oblongata. The co-localization of fibers containing SP or MET was found in most of the nuclei/tracts of the alpaca brainstem. This close neuroanatomical relationship suggests multiple physiological interactions between both neuropeptides. The distribution of the cell bodies containing SP was very restricted (cell bodies were only observed in a few nuclei located in the mesencephalon and medulla oblongata), whereas MET-Ir perikarya showed a moderately widespread distribution in the mesencephalon, pons and medulla oblongata. CONCLUSIONS: This study increases the knowledge on the neuroanatomical distribution/relationship of the tachykininergic (SP) and enkephalinergic (MET) systems in the alpaca central nervous system.


Assuntos
Camelídeos Americanos , Animais , Tronco Encefálico/metabolismo , Camelídeos Americanos/metabolismo , Diencéfalo/metabolismo , Encefalina Metionina/metabolismo , Masculino , Substância P
15.
Environ Pollut ; 287: 117151, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34020261

RESUMO

Fuel additive methylcyclopentadienyl manganese tricarbonyl (MMT) is counted as an organic manganese (Mn)-derived compound. The toxic effects of Mn (alone and complexed) on dopaminergic (DA) neurotransmission have been investigated in both cellular and animal models. However, the impact of environmentally relevant Mn exposure on DA neurodevelopment is rather poorly understood. In the present study, the MMT dose of 100 µM (about 5 mg Mn/L) caused up-regulation of DA-related genes in association with cell body swelling and increase in the number of DA neurons of the ventral diencephalon subpopulation DC2. Furthermore, our analysis identified significant brain Mn bioaccumulation and enhancement of total dopamine levels in association with locomotor hyperactivity. Although DA levels were restored at adulthood, we observed a deficit in the acquisition and consolidation of memory. Collectively, these findings suggest that developmental exposure to low-level MMT-derived Mn is responsible for the selective alteration of diencephalic DA neurons and with long-lasting effects on fish explorative behaviour in adulthood.


Assuntos
Manganês , Compostos Organometálicos , Animais , Diencéfalo , Neurônios Dopaminérgicos , Manganês/toxicidade , Peixe-Zebra
17.
BMC Neurol ; 21(1): 178, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33902491

RESUMO

BACKGROUND: Top of the basilar syndrome is a rare, heterogeneous disorder that has previously only been described in the setting of acute ischemic stroke in predominantly elderly patients. We present the first reported case of traumatic brain injury (TBI) causing ischemia in a top of the basilar distribution. CASE PRESENTATION: A 19-year-old woman suffered an acute subdural hematoma and sustained hypoxemia after being struck by a motor vehicle. Neurosurgical evacuation of the hematoma was undertaken. Magnetic resonance imaging revealed ischemic injury in the midbrain and diencephalic structures fitting a top of the basilar distribution. No associated vascular injury was identified. The patient was eventually discharged in a state of persistent unresponsive wakefulness. CONCLUSIONS: Ischemia in a top of the basilar distribution may occur in the setting of TBI. A high degree of clinical suspicion is required to identify this disorder. Further study of the complex inflammatory microenvironment and associated tissue perfusion dynamics in TBI are needed in order to elucidate the mechanisms underlying ischemic injury patterns, develop management paradigms and predict prognosis.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/patologia , Isquemia Encefálica/patologia , Diencéfalo/patologia , Mesencéfalo/patologia , Isquemia Encefálica/etiologia , Feminino , Hematoma Subdural Agudo/etiologia , Humanos , Imageamento por Ressonância Magnética , Adulto Jovem
18.
Neuron ; 109(10): 1721-1738.e4, 2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-33823137

RESUMO

Basal ganglia play a central role in regulating behavior, but the organization of their outputs to other brain areas is incompletely understood. We investigate the largest output nucleus, the substantia nigra pars reticulata (SNr), and delineate the organization and physiology of its projection populations in mice. Using genetically targeted viral tracing and whole-brain anatomical analysis, we identify over 40 SNr targets that encompass a roughly 50-fold range of axonal densities. Retrograde tracing from the volumetrically largest targets indicates that the SNr contains segregated subpopulations that differentially project to functionally distinct brain stem regions. These subpopulations are electrophysiologically specialized and topographically organized and collateralize to common diencephalon targets, including the motor and intralaminar thalamus as well as the pedunculopontine nucleus and the midbrain reticular formation. These findings establish that SNr signaling is organized as dense, parallel outputs to specific brain stem targets concurrent with extensive collateral branches that encompass the majority of SNr axonal boutons.


Assuntos
Gânglios da Base/citologia , Tronco Encefálico/citologia , Diencéfalo/citologia , Neurônios/fisiologia , Animais , Gânglios da Base/fisiologia , Tronco Encefálico/fisiologia , Diencéfalo/fisiologia , Potenciais Evocados , Camundongos , Camundongos Endogâmicos C57BL , Vias Neurais/citologia , Vias Neurais/fisiologia
19.
J Neurosci ; 41(18): 4141-4157, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33731451

RESUMO

Zebrafish models are used increasingly to study the molecular pathogenesis of Parkinson's disease (PD), owing to the extensive array of techniques available for their experimental manipulation and analysis. The ascending dopaminergic projection from the posterior tuberculum (TPp; diencephalic populations DC2 and DC4) to the subpallium is considered the zebrafish correlate of the mammalian nigrostriatal projection, but little is known about the neurophysiology of zebrafish DC2/4 neurons. This is an important knowledge gap, because autonomous activity in mammalian substantia nigra (SNc) dopaminergic neurons contributes to their vulnerability in PD models. Using a new transgenic zebrafish line to label living dopaminergic neurons, and a novel brain slice preparation, we conducted whole-cell patch clamp recordings of DC2/4 neurons from adult zebrafish of both sexes. Zebrafish DC2/4 neurons share many physiological properties with mammalian dopaminergic neurons, including the cell-autonomous generation of action potentials. However, in contrast to mammalian dopaminergic neurons, the pacemaker driving intrinsic rhythmic activity in zebrafish DC2/4 neurons does not involve calcium conductances, hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, or sodium leak currents. Instead, voltage clamp recordings and computational models show that interactions between three components - a small, predominantly potassium, leak conductance, voltage-gated sodium channels, and voltage-gated potassium channels - are sufficient for pacemaker activity in zebrafish DC2/4 neurons. These results contribute to understanding the comparative physiology of the dopaminergic system and provide a conceptual basis for interpreting data derived from zebrafish PD models. The findings further suggest new experimental opportunities to address the role of dopaminergic pacemaker activity in the pathogenesis of PD.SIGNIFICANCE STATEMENT Posterior tuberculum (TPp) DC2/4 dopaminergic neurons are considered the zebrafish correlate of mammalian substantia nigra (SNc) neurons, whose degeneration causes the motor signs of Parkinson's disease (PD). Our study shows that DC2/4 and SNc neurons share a number of electrophysiological properties, including depolarized membrane potential, high input resistance, and continual, cell-autonomous pacemaker activity, that strengthen the basis for the increasing use of zebrafish models to study the molecular pathogenesis of PD. The mechanisms driving pacemaker activity differ between DC2/4 and SNc neurons, providing: (1) experimental opportunities to dissociate the contributions of intrinsic activity and underlying pacemaker currents to pathogenesis; and (2) essential information for the design and interpretation of studies using zebrafish PD models.


Assuntos
Relógios Biológicos/fisiologia , Neurônios Dopaminérgicos/fisiologia , Peixe-Zebra/fisiologia , Potenciais de Ação/fisiologia , Animais , Animais Geneticamente Modificados , Sinalização do Cálcio/fisiologia , Diencéfalo/fisiologia , Feminino , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/fisiologia , Masculino , Neostriado/fisiologia , Vias Neurais/fisiologia , Técnicas de Patch-Clamp , Canais de Potássio de Abertura Dependente da Tensão da Membrana/fisiologia , Substância Negra/fisiologia , Canais de Sódio Disparados por Voltagem/fisiologia
20.
Blood ; 137(20): 2756-2769, 2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-33619517

RESUMO

During early embryonic development in mammals, including humans and mice, megakaryocytes (Mks) first originate from primitive hematopoiesis in the yolk sac. These embryonic Mks (eMks) circulate in the vasculature with unclear function. Herein, we report that podoplanin (PDPN), the ligand of C-type lectin-like receptor (CLEC-2) on Mks/platelets, is temporarily expressed in neural tissue during midgestation in mice. Loss of PDPN or CLEC-2 resulted in aneurysms and spontaneous hemorrhage, specifically in the lower diencephalon during midgestation. Surprisingly, more eMks/platelets had enhanced granule release and localized to the lower diencephalon in mutant mouse embryos than in wild-type littermates before hemorrhage. We found that PDPN counteracted the collagen-1-induced secretion of angiopoietin-1 from fetal Mks, which coincided with enhanced TIE-2 activation in aneurysm-like sprouts of PDPN-deficient embryos. Blocking platelet activation prevented the PDPN-deficient embryo from developing vascular defects. Our data reveal a new role for PDPN in regulating eMk function during midgestation.


Assuntos
Encéfalo/irrigação sanguínea , Aneurisma Intracraniano/etiologia , Megacariócitos/patologia , Glicoproteínas de Membrana/deficiência , Aneurisma Roto/embriologia , Aneurisma Roto/etiologia , Angiopoietina-1/metabolismo , Animais , Encéfalo/embriologia , Células Cultivadas , Hemorragia Cerebral/embriologia , Hemorragia Cerebral/etiologia , Colágeno/farmacologia , Diencéfalo/irrigação sanguínea , Diencéfalo/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Idade Gestacional , Aneurisma Intracraniano/embriologia , Aneurisma Intracraniano/genética , Aneurisma Intracraniano/patologia , Lectinas Tipo C/deficiência , Lectinas Tipo C/genética , Lectinas Tipo C/fisiologia , Megacariócitos/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/fisiologia , Camundongos , Camundongos Knockout , Neovascularização Patológica/genética , Neovascularização Patológica/fisiopatologia , Neovascularização Fisiológica/fisiologia , Ativação Plaquetária , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Receptor TIE-2/metabolismo
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