RESUMO
Urine release (micturition) serves an essential physiological function as well as a critical role in social communication in many animals. Here, we show a combined effect of olfaction and social hierarchy on micturition patterns in adult male mice, confirming the existence of a micturition control center that integrates pro- and anti-micturition cues. Furthermore, we demonstrate that a cluster of neurons expressing corticotropin-releasing hormone (Crh) in the pontine micturition center (PMC) is electrophysiologically distinct from their Crh-negative neighbors and sends glutamatergic projections to the spinal cord. The activity of PMC Crh-expressing neurons correlates with and is sufficient to drive bladder contraction, and when silenced impairs micturition behavior. These neurons receive convergent input from widespread higher brain areas that are capable of carrying diverse pro- and anti-micturition signals, and whose activity modulates hierarchy-dependent micturition. Taken together, our results indicate that PMC Crh-expressing neurons are likely the integration center for context-dependent micturition behavior.
Assuntos
Hormônio Liberador da Corticotropina/metabolismo , Contração Muscular/fisiologia , Neurônios/fisiologia , Ponte/fisiologia , Bexiga Urinária/fisiologia , Micção/fisiologia , Animais , Feminino , Ácido Glutâmico/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Ponte/citologia , Olfato , Medula Espinal/citologia , Medula Espinal/fisiologia , Bexiga Urinária/inervaçãoRESUMO
Survival requires the selection of appropriate behaviour in response to threats, and dysregulated defensive reactions are associated with psychiatric illnesses such as post-traumatic stress and panic disorder1. Threat-induced behaviours, including freezing and flight, are controlled by neuronal circuits in the central amygdala (CeA)2; however, the source of neuronal excitation of the CeA that contributes to high-intensity defensive responses is unknown. Here we used a combination of neuroanatomical mapping, in vivo calcium imaging, functional manipulations and electrophysiology to characterize a previously unknown projection from the dorsal peduncular (DP) prefrontal cortex to the CeA. DP-to-CeA neurons are glutamatergic and specifically target the medial CeA, the main amygdalar output nucleus mediating conditioned responses to threat. Using a behavioural paradigm that elicits both conditioned freezing and flight, we found that CeA-projecting DP neurons are activated by high-intensity threats in a context-dependent manner. Functional manipulations revealed that the DP-to-CeA pathway is necessary and sufficient for both avoidance behaviour and flight. Furthermore, we found that DP neurons synapse onto neurons within the medial CeA that project to midbrain flight centres. These results elucidate a non-canonical top-down pathway regulating defensive responses.
Assuntos
Aprendizagem da Esquiva , Núcleo Central da Amígdala , Vias Neurais , Neurônios , Aprendizagem da Esquiva/fisiologia , Núcleo Central da Amígdala/citologia , Núcleo Central da Amígdala/fisiologia , Neurônios/fisiologia , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/fisiologia , Fármacos Atuantes sobre Aminoácidos Excitatórios/farmacologia , Ácido Glutâmico/metabolismo , Vias Neurais/fisiologia , Cálcio/análise , Eletrofisiologia , Ponte/citologia , Ponte/fisiologiaRESUMO
The hippocampus has a major role in encoding and consolidating long-term memories, and undergoes plastic changes during sleep1. These changes require precise homeostatic control by subcortical neuromodulatory structures2. The underlying mechanisms of this phenomenon, however, remain unknown. Here, using multi-structure recordings in macaque monkeys, we show that the brainstem transiently modulates hippocampal network events through phasic pontine waves known as pontogeniculooccipital waves (PGO waves). Two physiologically distinct types of PGO wave appear to occur sequentially, selectively influencing high-frequency ripples and low-frequency theta events, respectively. The two types of PGO wave are associated with opposite hippocampal spike-field coupling, prompting periods of high neural synchrony of neural populations during periods of ripple and theta instances. The coupling between PGO waves and ripples, classically associated with distinct sleep stages, supports the notion that a global coordination mechanism of hippocampal sleep dynamics by cholinergic pontine transients may promote systems and synaptic memory consolidation as well as synaptic homeostasis.
Assuntos
Corpos Geniculados/fisiologia , Hipocampo/fisiologia , Lobo Occipital/fisiologia , Ponte/fisiologia , Sono/fisiologia , Ritmo Teta/fisiologia , Animais , Pareamento Cromossômico/fisiologia , Feminino , Homeostase , Macaca/fisiologia , Consolidação da Memória/fisiologia , Plasticidade Neuronal , Fases do Sono/fisiologiaRESUMO
Development of effective targeted cancer therapies is fundamentally limited by our molecular understanding of disease pathogenesis. Diffuse intrinsic pontine glioma (DIPG) is a fatal malignancy of the childhood pons characterized by a unique substitution to methionine in histone H3 at lysine 27 (H3K27M) that results in globally altered epigenetic marks and oncogenic transcription. Through primary DIPG tumor characterization and isogenic oncohistone expression, we show that the same H3K27M mutation displays distinct modes of oncogenic reprogramming and establishes distinct enhancer architecture depending upon both the variant of histone H3 and the cell context in which the mutation occurs. Compared with non-malignant pediatric pontine tissue, we identify and functionally validate both shared and variant-specific pathophysiology. Altogether, we provide a powerful resource of epigenomic data in 25 primary DIPG samples and 5 rare normal pediatric pontine tissue samples, revealing clinically relevant functional distinctions previously unidentified in DIPG.
Assuntos
Glioma Pontino Intrínseco Difuso/genética , Histonas/genética , Encéfalo/patologia , Neoplasias Encefálicas/genética , Reprogramação Celular/genética , Glioma Pontino Intrínseco Difuso/metabolismo , Elementos Facilitadores Genéticos/genética , Epigênese Genética/genética , Epigenômica , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Glioma/genética , Glioma/metabolismo , Humanos , Lisina/genética , Mutação/genética , Ponte/metabolismo , Transdução de Sinais , Transcriptoma/fisiologiaRESUMO
Neuropeptide S (NPS) was postulated to be a wake-promoting neuropeptide with unknown mechanism, and a mutation in its receptor (NPSR1) causes the short sleep duration trait in humans. We investigated the role of different NPS+ nuclei in sleep/wake regulation. Loss-of-function and chemogenetic studies revealed that NPS+ neurons in the parabrachial nucleus (PB) are wake-promoting, whereas peri-locus coeruleus (peri-LC) NPS+ neurons are not important for sleep/wake modulation. Further, we found that a NPS+ nucleus in the central gray of the pons (CGPn) strongly promotes sleep. Fiber photometry recordings showed that NPS+ neurons are wake-active in the CGPn and wake/REM-sleep active in the PB and peri-LC. Blocking NPS-NPSR1 signaling or knockdown of Nps supported the function of the NPS-NPSR1 pathway in sleep/wake regulation. Together, these results reveal that NPS and NPS+ neurons play dichotomous roles in sleep/wake regulation at both the molecular and circuit levels.
Assuntos
Neuropeptídeos , Sono , Humanos , Sono/fisiologia , Ponte/fisiologia , Locus Cerúleo/fisiologia , Neurônios/metabolismo , Neuropeptídeos/metabolismo , Receptores Acoplados a Proteínas G/metabolismoRESUMO
The rhombicbrain (rhombencephalon or intermediate sector) is the vertebrate central nervous system part between the forebrain-midbrain (rostral sector) and spinal cord (caudal sector), and it has three main divisions: pons, cerebellum, and medulla. Using a data-driven approach, here we examine intrinsic rhombicbrain (intrarhombicbrain) network architecture that in rat consists of 52,670 possible axonal connections between 230 gray matter regions (115 bilaterally symmetrical pairs). Our analysis indicates that only 8,089 (15.4%) of these connections exist. Multiresolution consensus cluster analysis yields a nested hierarchy model of rhombicbrain subsystems that at the top level are associated with 1) the cerebellum and vestibular nuclei, 2) orofacial-pharyngeal-visceral integration, and 3) auditory connections; the bottom level has 68 clusters, ranging in size from 2 to 11 regions. The model provides a basis for functional hypothesis development and interrogation. More granular network analyses performed on the intrinsic connectivity of individual and combined main rhombicbrain divisions (pons, cerebellum, medulla, pons + cerebellum, and pons + medulla) demonstrate the mutability of network architecture in response to the addition or subtraction of connections. Clear differences between the structure-function network architecture of the rhombicbrain and forebrain-midbrain are discussed, with a stark comparison provided by the subsystem and small-world organization of the cerebellar cortex and cerebral cortex. Future analysis of the connections within and between the forebrain-midbrain and rhombicbrain will provide a model of brain neural network architecture in a mammal.
Assuntos
Cerebelo , Ponte , Ratos , Animais , Prosencéfalo , Sistema Nervoso Central , MamíferosRESUMO
Axonal projections from layer V neurons of distinct neocortical areas are topographically organized into discrete clusters within the pontine nuclei during the establishment of voluntary movements. However, the molecular determinants controlling corticopontine connectivity are insufficiently understood. Here, we show that an intrinsic cortical genetic program driven by Nr2f1 graded expression is directly implicated in the organization of corticopontine topographic mapping. Transgenic mice lacking cortical expression of Nr2f1 and exhibiting areal organization defects were used as model systems to investigate the arrangement of corticopontine projections. By combining three-dimensional digital brain atlas tools, Cre-dependent mouse lines and axonal tracing, we show that Nr2f1 expression in postmitotic neurons spatially and temporally controls somatosensory topographic projections, whereas expression in progenitor cells influences the ratio between corticopontine and corticospinal fibres passing the pontine nuclei. We conclude that cortical gradients of area-patterning genes are directly implicated in the establishment of a topographic somatotopic mapping from the cortex onto pontine nuclei.
Assuntos
Mapeamento Encefálico , Ponte , Animais , Axônios , Córtex Cerebral , Camundongos , Vias Neurais/fisiologia , Neurônios , Ponte/fisiologiaRESUMO
This study investigates abnormalities in cerebellar-cerebral static and dynamic functional connectivity among patients with acute pontine infarction, examining the relationship between these connectivity changes and behavioral dysfunction. Resting-state functional magnetic resonance imaging was utilized to collect data from 45 patients within seven days post-pontine infarction and 34 normal controls. Seed-based static and dynamic functional connectivity analyses identified divergences in cerebellar-cerebral connectivity features between pontine infarction patients and normal controls. Correlations between abnormal functional connectivity features and behavioral scores were explored. Compared to normal controls, left pontine infarction patients exhibited significantly increased static functional connectivity within the executive, affective-limbic, and motor networks. Conversely, right pontine infarction patients demonstrated decreased static functional connectivity in the executive, affective-limbic, and default mode networks, alongside an increase in the executive and motor networks. Decreased temporal variability of dynamic functional connectivity was observed in the executive and default mode networks among left pontine infarction patients. Furthermore, abnormalities in static and dynamic functional connectivity within the executive network correlated with motor and working memory performance in patients. These findings suggest that alterations in cerebellar-cerebral static and dynamic functional connectivity could underpin the behavioral dysfunctions observed in acute pontine infarction patients.
Assuntos
Infartos do Tronco Encefálico , Cerebelo , Imageamento por Ressonância Magnética , Vias Neurais , Ponte , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Cerebelo/fisiopatologia , Cerebelo/diagnóstico por imagem , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Ponte/diagnóstico por imagem , Ponte/fisiopatologia , Infartos do Tronco Encefálico/fisiopatologia , Infartos do Tronco Encefálico/diagnóstico por imagem , Idoso , Adulto , Córtex Cerebral/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Rede Nervosa/diagnóstico por imagemRESUMO
Comparison of treatment strategies in de novo pediatric acute lymphoblastic leukemia (ALL) requires standardized measures of efficacy. Key parameters that define disease-related events, including complete remission (CR), treatment failure (TF; not achieving CR), and relapse (loss of CR) require an updated consensus incorporating modern diagnostics. We collected the definitions of CR, TF, and relapse from recent and current pediatric clinical trials for the treatment of ALL, including the key components of response evaluation (timing, anatomic sites, detection methods, and thresholds) and found significant heterogeneity, most notably in the definition of TF. Representatives of the major international ALL clinical trial groups convened to establish consensus definitions. CR should be defined at a time point no earlier than at the end of induction and should include the reduction of blasts below a specific threshold in bone marrow and extramedullary sites, incorporating minimal residual disease (MRD) techniques for marrow evaluations. TF should be defined as failure to achieve CR by a prespecified time point in therapy. Relapse can only be defined in patients who have achieved CR and must include a specific threshold of leukemic cells in the bone marrow confirmed by MRD, the detection of central nervous system leukemia, or documentation of extramedullary disease. Definitions of TF and relapse should harmonize with eligibility criteria for clinical trials in relapsed/refractory ALL. These consensus definitions will enhance the ability to compare outcomes across pediatric ALL trials and facilitate development of future international collaborative trials.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Consenso , Humanos , Neoplasia Residual/diagnóstico , Ponte , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recidiva , Indução de Remissão , Falha de TratamentoRESUMO
The term Pontocerebellar Hypoplasia (PCH) was initially used to designate a heterogeneous group of fetal-onset genetic neurodegenerative disorders. As a descriptive term, PCH refers to pons and cerebellum of reduced volume. In addition to the classic PCH types described in OMIM, many other disorders can result in a similar imaging appearance. This study aims to review imaging, clinical and genetic features and underlying etiologies of a cohort of children with PCH on imaging. We systematically reviewed brain images and clinical charts of 38 patients with radiologic evidence of PCH. Our cohort included 21 males and 17 females, with ages ranging between 8 days to 15 years. All individuals had pons and cerebellar vermis hypoplasia, and 63% had cerebellar hemisphere hypoplasia. Supratentorial anomalies were found in 71%. An underlying etiology was identified in 68% and included chromosomal (21%), monogenic (34%) and acquired (13%) causes. Only one patient had pathogenic variants in an OMIM listed PCH gene. Outcomes were poor regardless of etiology, though no one had regression. Approximately one third of patients deceased at a median age of 8 months. All individuals had global developmental delay, 50% were non-verbal, 64% were non-ambulatory and 45% required gastrostomy feeding. This cohort demonstrates that radiologic PCH has heterogenous etiologies and the "classic" OMIM-listed PCH genes underlie only a minority of cases. Broad genetic testing, including chromosomal microarray and exome or multigene panels, is recommended in individuals with PCH-like imaging appearance. Our results strongly suggest that the term PCH should be used to designate radiologic findings, and not to imply neurogenerative disorders.
Assuntos
Doenças Cerebelares , Cerebelo/anormalidades , Malformações do Sistema Nervoso , Masculino , Criança , Feminino , Humanos , Lactente , Doenças Cerebelares/patologia , Cerebelo/patologia , Ponte/diagnóstico por imagem , Imageamento por Ressonância Magnética , Deficiências do DesenvolvimentoRESUMO
BACKGROUND: Functional anatomical research proposed the existence of a bilateral trigeminal ascending system although the anatomy trajectories of the trigeminothalamic connections cranial to the pons remain largely elusive. This study therefore aimed to clarify the anatomical distributions of the trigeminothalamic connections in humans. METHODS: Advanced deterministic tractography to an averaged template of diffusion tensor imaging data from 1065 subjects from the Human Connectome Project was used. Seedings masks were placed in Montreal Neurological Institute standard space by use of the BigBrain histological dataset. Waypoint masks of the sensory thalamus was obtained from the Brainnetome Atlas. RESULTS: Tractography results were validated by use of the BigBrain histological dataset and Polarized Light Imaging microscopy. The trigeminothalamic tract bifurcated into a decussating ventral and a non-decussating dorsal tract. The ventral and dorsal tracts ascended to the contralateral thalamus and ipsilateral thalamus and reflected the ventral trigeminothalamic tract and the dorsal trigeminothalamic tract, respectively. The projection of the ventral trigeminothalamic tract and the dorsal trigeminothalamic tract to both thalami confirm the existence of a bilateral trigeminothalamic system in humans. CONCLUSIONS: Because our study is strictly anatomical, no further conclusions can be drawn with regard to physiological functionality. Future research should explore if the dorsal trigeminothalamic tract and the ventral trigeminothalamic tract actually transmit signals from noxious stimuli, this offers potential in understanding and possibly treating neuropathology in the orofacial region.
Assuntos
Conectoma , Humanos , Imagem de Tensor de Difusão , Ponte , Crânio , Tálamo/diagnóstico por imagemRESUMO
OBJECTIVES: The presence of dysphagia in stroke is associated with mortality and morbidity. The aim of this retrospective study is to present the relationship between dysphagia and the demographic characteristics of the patient, and the type and localisation of brain lesion in the acute period in stroke patients with dysphagia. MATERIALS AND METHODS: The data of 284 patients who had stroke-related dysphagia, had a disease duration 1-3 months, had no history of swallowing dysfunction before the event, and had their brain MRI/CT reports in the hospital were included. RESULTS: The rate of tube-dependent oral areas was higher in the lesions located in the pons and the medulla than in the lesions located in the MCA cortex, the basal ganglia, and the cerebellum (p Ë 0.001, p = 0.032 and p = 0.011, respectively) and the percentage of those fed with NG + TPN + PEG was statistically significantly higher (p = 0.002, p = 0.032 and p = 0.011, respectively). History of pneumonia was found to be statistically significantly higher in the lesions located in the pons and the medulla than in the lesions located in the MCA cortex, ACA cortex, PCA cortex, the basal ganglia, periventricular white matter, the thalamus, the cerebellum, and the midbrain (p Ë 0.001, p = 0.005, p = 0.023, p Ë 0.001, p = 0.023, p = 0.001, p = 0.011 and p = 0.023, respectively). CONCLUSION: In conclusion, although lesion localisation in the acute period in patients with dysphagia varied in terms of clinical swallowing evaluation findings, weight loss, pneumonia history, the rate of tube-dependent intake, were shown to be higher in patients who had lesions in the pons and the medulla, which is a finding that should be considered in the clinical follow-up of acute stroke patients with lesions in the pons and the medulla.
Assuntos
Transtornos de Deglutição , Pneumonia , Acidente Vascular Cerebral , Humanos , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/complicações , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia , Ponte/diagnóstico por imagem , Ponte/patologia , Pneumonia/complicaçõesRESUMO
Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a discrete nosological entity characterized by punctate and curvilinear gadolinium enhancement "peppering" the pons and a strong response to steroids. MRI images typically show pontine and cerebellar punctate-enhancing lesions, which occasionally spread up to the juxtacortical areas and down to the spinal cord. Interestingly, the more distant the lesion is from the pons, the less intense they become. Herein, we describe an extremely rare case of CLIPPERS presenting with predominant spinal cord involvement; then, we searched in the literature the available cases with a similar presentation. Our case focuses attention on a rare MRI CLIPPERS presentation. Since CLIPPERS has a dramatic response to corticosteroid treatment, it is fundamental to promptly recognize its MRI pattern to start treatment as soon as possible.
Assuntos
Imageamento por Ressonância Magnética , Medula Espinal , Humanos , Ponte/diagnóstico por imagem , Ponte/patologia , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologiaRESUMO
BACKGROUND: The nucleus incertus (NI) was originally described by Streeter in 1903, as a midline region in the floor of the fourth ventricle of the human brain with an 'unknown' function. More than a century later, the neuroanatomy of the NI has been described in lower vertebrates, but not in humans. Therefore, we examined the neurochemical anatomy of the human NI using markers, including the neuropeptide, relaxin-3 (RLN3), and began to explore the distribution of the NI-related RLN3 innervation of the hippocampus. METHODS: Histochemical staining of serial, coronal sections of control human postmortem pons was conducted to reveal the presence of the NI by detection of immunoreactivity (IR) for the neuronal markers, microtubule-associated protein-2 (MAP2), glutamic acid dehydrogenase (GAD)-65/67 and corticotrophin-releasing hormone receptor 1 (CRHR1), and RLN3, which is highly expressed in NI neurons in diverse species. RLN3 and vesicular GABA transporter 1 (vGAT1) mRNA were detected by fluorescent in situ hybridization. Pons sections containing the NI from an AD case were immunostained for phosphorylated-tau, to explore potential relevance to neurodegenerative diseases. Lastly, sections of the human hippocampus were stained to detect RLN3-IR and somatostatin (SST)-IR. RESULTS: In the dorsal, anterior-medial region of the human pons, neurons containing RLN3- and MAP2-IR, and RLN3/vGAT1 mRNA-positive neurons were observed in an anatomical pattern consistent with that of the NI in other species. GAD65/67- and CRHR1-immunopositive neurons were also detected within this area. Furthermore, RLN3- and AT8-IR were co-localized within NI neurons of an AD subject. Lastly, RLN3-IR was detected in neurons within the CA1, CA2, CA3 and DG areas of the hippocampus, in the absence of RLN3 mRNA. In the DG, RLN3- and SST-IR were co-localized in a small population of neurons. CONCLUSIONS: Aspects of the anatomy of the human NI are shared across species, including a population of stress-responsive, RLN3-expressing neurons and a RLN3 innervation of the hippocampus. Accumulation of phosphorylated-tau in the NI suggests its possible involvement in AD pathology. Further characterization of the neurochemistry of the human NI will increase our understanding of its functional role in health and disease.
Assuntos
Ponte , Humanos , Ponte/metabolismo , Masculino , Hipocampo/química , Hipocampo/metabolismo , Feminino , Relaxina/metabolismo , Relaxina/genética , Idoso , Neurônios/química , Memória/fisiologia , Proteínas Associadas aos Microtúbulos/metabolismo , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Glutamato Descarboxilase/metabolismo , Glutamato Descarboxilase/genética , Receptores de Hormônio Liberador da CorticotropinaRESUMO
BACKGROUND: Miliary tuberculosis (TB) is a lethal hematogenous spread form of mycobacterium tuberculosis with approximately 15-20% mortality rate in children. The present report highlights the clinical manifestations of an unusual presentation of miliary tuberculosis in a 12-year-old girl. CASE PRESENTATION: In this case, extensive lung involvement was presented despite the absence of respiratory symptoms. Also, some central hypo-intense with hyper-intense rim nodules were detected in the brain's pons, right cerebral peduncles and lentiform nucleus. CONCLUSION: The results of this study showed that severe miliary TB may occur even in a person who received the Bacille Calmette-Guérin (BCG) vaccine.
Assuntos
Mycobacterium tuberculosis , Tuberculose Miliar , Criança , Feminino , Humanos , Tuberculose Miliar/diagnóstico , Tuberculose Miliar/tratamento farmacológico , Vacina BCG , PonteRESUMO
The release of urine, or micturition, serves a fundamental physiological function and, in many species, is critical for social communication. In mice, the pattern of urine release is modulated by external and internal factors and transmitted to the spinal cord via the pontine micturition center (PMC). Here, we exploited a behavioral paradigm in which mice, depending on strain, social experience, and sensory context, either vigorously cover an arena with small urine spots or deposit urine in a few isolated large spots. We refer to these micturition modes as, respectively, high and low territory-covering micturition (TCM) and find that the presence of a urine stimulus robustly induces high TCM in socially isolated mice. Comparison of the brain networks activated by social isolation and by urine stimuli to those upstream of the PMC identified the lateral hypothalamic area as a potential modulator of micturition modes. Indeed, chemogenetic manipulations of the lateral hypothalamus can switch micturition behavior between high and low TCM, overriding the influence of social experience and sensory context. Our results suggest that both inhibitory and excitatory signals arising from a network upstream of the PMC are integrated to determine context- and social-experience-dependent micturition patterns.
Assuntos
Hipotálamo/fisiologia , Isolamento Social/psicologia , Micção/fisiologia , Animais , Encéfalo/fisiologia , Comunicação , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Ponte/fisiologia , Reflexo/fisiologia , Medula Espinal/fisiologia , Bexiga Urinária/fisiologia , Micção/genéticaRESUMO
BACKGROUND: Based on their anatomical location, rostral projections of nuclei are classified as ascending circuits, while caudal projections are classified as descending circuits. Upper brainstem neurons participate in complex information processing and specific sub-populations preferentially project to participating ascending or descending circuits. Cholinergic neurons in the upper brainstem have extensive collateralizations in both ascending and descending circuits; however, their single-cell projection patterns remain unclear because of the lack of comprehensive characterization of individual neurons. RESULTS: By combining fluorescent micro-optical sectional tomography with sparse labeling, we acquired a high-resolution whole-brain dataset of pontine-tegmental cholinergic neurons (PTCNs) and reconstructed their detailed morphology using semi-automatic reconstruction methods. As the main source of acetylcholine in some subcortical areas, individual PTCNs had abundant axons with lengths up to 60 cm and 5000 terminals and innervated multiple brain regions from the spinal cord to the cortex in both hemispheres. Based on various collaterals in the ascending and descending circuits, individual PTCNs were grouped into four subtypes. The morphology of cholinergic neurons in the pedunculopontine nucleus was more divergent, whereas the laterodorsal tegmental nucleus neurons contained richer axonal branches and dendrites. In the ascending circuits, individual PTCNs innervated the thalamus in three different patterns and projected to the cortex via two separate pathways. Moreover, PTCNs targeting the ventral tegmental area and substantia nigra had abundant collaterals in the pontine reticular nuclei, and these two circuits contributed oppositely to locomotion. CONCLUSIONS: Our results suggest that individual PTCNs have abundant axons, and most project to various collaterals in the ascending and descending circuits simultaneously. They target regions with multiple patterns, such as the thalamus and cortex. These results provide a detailed organizational characterization of cholinergic neurons to understand the connexional logic of the upper brainstem.
Assuntos
Axônios , Tronco Encefálico , Tronco Encefálico/fisiologia , Axônios/fisiologia , Ponte/anatomia & histologia , Ponte/fisiologia , Encéfalo , Neurônios ColinérgicosRESUMO
This study aimed to investigate, for the first time, the potential role of the gigantocellular nucleus, a component of the reticular formation, in the pathogenetic mechanism of Sudden Infant Death Syndrome (SIDS), an event frequently ascribed to failure to arouse from sleep. This research was motivated by previous experimental studies demonstrating the gigantocellular nucleus involvement in regulating the sleep-wake cycle. We analyzed the brains of 48 infants who died suddenly within the first 7 months of life, including 28 SIDS cases and 20 controls. All brains underwent a thorough histological and immunohistochemical examination, focusing specifically on the gigantocellular nucleus. This examination aimed to characterize its developmental cytoarchitecture and tyrosine hydroxylase expression, with particular attention to potential associations with SIDS risk factors. In 68% of SIDS cases, but never in controls, we observed hypoplasia of the pontine portion of the gigantocellular nucleus. Alterations in the catecholaminergic system were present in 61% of SIDS cases but only in 10% of controls. A strong correlation was observed between these findings and maternal smoking in SIDS cases when compared with controls. In conclusion we believe that this study sheds new light on the pathogenetic processes underlying SIDS, particularly in cases associated with maternal smoking during pregnancy.
Assuntos
Morte Súbita do Lactente , Humanos , Morte Súbita do Lactente/patologia , Morte Súbita do Lactente/etiologia , Feminino , Masculino , Lactente , Fatores de Risco , Estudos de Casos e Controles , Recém-Nascido , Gravidez , Tirosina 3-Mono-Oxigenase/metabolismo , Ponte/patologia , Ponte/metabolismo , Formação Reticular/patologia , Formação Reticular/metabolismoRESUMO
Surgeries for brainstem lesions and adjacent areas needs meticulous manipulation in the profoundly deep surgical field. Moreover, it is associated with a high risk of complications pertinent to resection. The opportunity for a surgeon to amass extensive surgical experience in these lesions is limited. Additionally, the reduced tissue mobility in the brainstem, compared to other lesions, makes selecting the optimal surgical approach critical. Preoperative simulation is pivotal in surmounting these challenges. However, the limitations of preoperative simulations should be recognized in accurately depicting diminutive vessels and cranial nerves around the brainstem. Incorporating intraoperative anatomical observations and data from intraoperative monitoring into a surgical strategy is imperative. Here, we present three cases in which we believe preoperative simulation was effective; a cavernous hemangioma of the brainstem, trochlear schwannoma, and diffuse midline glioma in the pons.
Assuntos
Hemangioma Cavernoso do Sistema Nervoso Central , Humanos , Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Tronco Encefálico/cirurgia , Ponte , Nervos Cranianos/patologia , Procedimentos NeurocirúrgicosRESUMO
Rett syndrome (RTT) is a severe neurodevelopmental disorder that mainly affects females due to silencing mutations in the X-linked MECP2 gene. One of the most troubling symptoms of RTT is breathing irregularity, including apneas, breath-holds, and hyperventilation. Mice with silencing mutations in Mecp2 exhibit breathing abnormalities similar to human patients and serve as useful models for studying mechanisms underlying breathing problems in RTT. Previous work implicated the pontine, respiratory-controlling Kölliker-Fuse (KF) in the breathing problems in RTT. The goal of this study was to test the hypothesis that inhibitory synaptic transmission is deficient in KF neurons from symptomatic male and female RTT mice. We performed whole cell voltage-clamp recordings from KF neurons in acute brain slices to examine spontaneous and electrically evoked inhibitory post-synaptic currents (IPSCs) in RTT mice and age- and sex-matched wild-type mice. The frequency of spontaneous IPSCs was reduced in KF neurons from male RTT mice but surprisingly not in female RTT mice. In addition, electrically evoked IPSCs were less reliable in KF neurons from male, but not female, RTT mice, which was positively correlated with paired-pulse facilitation, indicating decreased probability of release. KF neurons from male RTT mice were also more excitable and exhibited shorter-duration action potentials. Increased excitability of KF neurons from male mice was not explained by changes in axon initial segment length. These findings indicate impaired inhibitory neurotransmission and increased excitability of KF neurons in male but not female RTT mice and suggest that sex-dependent mechanisms contribute to breathing problems in RTT.NEW & NOTEWORTHY Kölliker-Fuse (KF) neurons in acute brain slices from male Rett syndrome (RTT) mice receive reduced inhibitory synaptic inputs compared with wild-type littermates. In female RTT mice, inhibitory transmission was not different in KF neurons compared with controls. The results from this study show that sex-specific alterations in synaptic transmission occur in the KF of RTT mice.