RESUMO
Discovered in 1865 by Jules Bernard Luys, the subthalamic nucleus is a set of small nuclei located in the diencephalon, inferior to the thalamus and superior to the substantia nigra, that can be visualized in a posterior coronal section. Histologically, it consists of neurons compactly distributed and filled with a large number of blood vessels and sparse myelinated fibers. This review presents an analysis of this anatomical region, considering what is most recent in the literature. Subthalamic neurons are excitatory and use glutamate as the neurotransmitter. In healthy individuals, these neurons are inhibited by nerve cells located in the side globus pallidus. However, if the fibers that make up the afferent circuit are damaged, the neurons become highly excitable, thus causing motor disturbances that can be classified as hyperkinetic, for example ballism and chorea, or hypokinetic, for example Parkinson disease (PD). The advent of deep brain stimulation has given the subthalamic nucleus great visibility. Studies reveal that the stimulation of this nucleus improves themotor symptoms of PD.
Assuntos
Núcleo Subtalâmico/anatomia & histologia , Núcleo Subtalâmico/anormalidades , Núcleo Subtalâmico/cirurgia , Doença de Parkinson , Substância Negra/anatomia & histologia , Córtex Cerebral/anatomia & histologia , Corpo Estriado/anatomia & histologia , Estimulação Encefálica Profunda/métodos , Globo Pálido/anatomia & histologia , Córtex Motor/anatomia & histologiaRESUMO
It is widely known that the catecholamine group is formed by dopamine, noradrenaline and adrenaline. Its synthesis is regulated by the enzyme called tyrosine hydroxylase. 3-hydroxytyramine/dopamine (DA) is a precursor of noradrenaline and adrenaline synthesis and acts as a neurotransmitter in the central nervous system. The three main nuclei, being the retrorubral field (A8 group), the substantia nigra pars compacta (A9 group) and the ventral tegmental area (A10 group), are arranged in the die-mesencephalic portion and are involved in three complex circuitries - the mesostriatal, mesolimbic and mesocortical pathways. These pathways are involved in behavioral manifestations, motricity, learning, reward and also in pathological conditions such as Parkinson's disease and schizophrenia. The aim of this study was to perform a morphological analysis of the A8, A9 and A10 groups in the common marmoset (Callithrix jacchus - a neotropical primate), whose morphological and functional characteristics support its suitability for use in biomedical research. Coronal sections of the marmoset brain were submitted to Nissl staining and TH-immunohistochemistry. The morphology of the neurons made it possible to subdivide the A10 group into seven distinct regions: interfascicular nucleus, raphe rostral linear nucleus and raphe caudal linear nucleus in the middle line; paranigral and parainterfascicular nucleus in the middle zone; the rostral portion of the ventral tegmental area nucleus and parabrachial pigmented nucleus located in the dorsolateral portion of the mesencephalic tegmentum. The A9 group was divided into four regions: substantia nigra compacta dorsal and ventral tiers; substantia nigra compacta lateral and medial clusters. No subdivisions were made for the A8 group. These results reveal that A8, A9 and A10 are phylogenetically stable across species. As such, further studies concerning such divisions are necessary in order to evaluate the occurrence of subdivisions that express DA in other primate species, with the aim of characterizing its functional relevance.
Assuntos
Substância Negra/anatomia & histologia , Substância Negra/enzimologia , Tegmento Mesencefálico/anatomia & histologia , Tegmento Mesencefálico/enzimologia , Tirosina 3-Mono-Oxigenase/metabolismo , Área Tegmentar Ventral/anatomia & histologia , Área Tegmentar Ventral/enzimologia , Animais , Comportamento , Callithrix , Imuno-Histoquímica , Aprendizagem , Masculino , Atividade Motora , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Neurônios/ultraestrutura , Núcleos da Rafe/anatomia & histologia , Núcleos da Rafe/citologia , Núcleos da Rafe/fisiologia , RecompensaRESUMO
The human brain undergoes non-uniform changes during aging. The substantia nigra (SN), the source of major dopaminergic pathways in the brain, is particularly vulnerable to changes in the progression of several age-related neurodegenerative diseases. To establish normative data for high-resolution imaging, and to further clinical and anatomical studies we analyzed SNs from 15 subjects aged 50-91 cognitively normal human subjects without signs of parkinsonism. Complete brains or brainstems with substantia nigra were formalin-fixed, celloidin-mounted, serially cut and Nissl-stained. The shapes of all SNs investigated were reconstructed using fast, high-resolution computer-assisted 3D reconstruction software. We found a negative correlation between age and SN volume (p = 0.04, rho = -0.53), with great variability in neuronal numbers and density across participants. The 3D reconstructions revealed SN inter- and intra-individual variability. Furthermore, we observed that human SN is a neuronal reticulum, rather than a group of isolated neuronal islands. Caution is required when using SN volume as a surrogate for SN status in individual subjects. The use of multimodal sequences including those for fiber tracts may enhance the value of imaging as a diagnostic tool to assess SN in vivo. Further studies with a larger sample size are needed for understanding the structure-function interaction of human SN.
Assuntos
Envelhecimento , Neurônios/citologia , Neurônios/fisiologia , Substância Negra/anatomia & histologia , Substância Negra/fisiologia , Idoso , Idoso de 80 Anos ou mais , Contagem de Células , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Substância Negra/citologiaRESUMO
In the present review we propose a model to explain the role of the basal ganglia in sensorimotor and cognitive functions based on a growing body of behavioural, anatomical, physiological, and neurochemical evidence accumulated over the last decades. This model proposes that the body and its surrounding environment are represented in the striatum in a fragmented and repeated way, like a mosaic consisting of the fragmented images of broken mirrors. Each fragment forms a functional unit representing articulated parts of the body with motion properties, objects of the environment which the subject can approach or manipulate, and locations the subject can move to. These units integrate the sensory properties and movements related to them. The repeated and widespread distribution of such units amplifies the combinatorial power of the associations among them. These associations depend on the phasic release of dopamine in the striatum triggered by the saliency of stimuli and will be reinforced by the rewarding consequences of the actions related to them. Dopamine permits synaptic plasticity in the corticostriatal synapses. The striatal units encoding the same stimulus/action send convergent projections to the internal segment of the globus pallidus (GPi) and to the substantia nigra pars reticulata (SNr) that stimulate or hold the action through a thalamus-frontal cortex pathway. According to this model, this is how the basal ganglia select actions based on environmental stimuli and store adaptive associations as nondeclarative memories such as motor skills, habits, and memories formed by Pavlovian and instrumental conditioning.
Assuntos
Gânglios da Base/anatomia & histologia , Gânglios da Base/fisiologia , Dopamina/fisiologia , Aprendizagem/fisiologia , Animais , Cognição/fisiologia , Dopamina/metabolismo , Humanos , Memória/fisiologia , Substância Negra/anatomia & histologia , Substância Negra/fisiologiaRESUMO
The ventral tegmental area (VTA) is a nodal link in reward circuitry. Based on its striatal output, it has been subdivided in a caudomedial part which targets the ventromedial striatum, and a lateral part which targets the ventrolateral striatum [Ikemoto S (2007) Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex. Brain Res Rev 56:27-78]. Whether these two VTA parts are interconnected and to what extent the VTA innervates the substantia nigra compacta (SNc) and retrorubral nucleus (RR) are critical issues for understanding information processing in the basal ganglia. Here, VTA projections to the VTA-nigral complex were examined in rats, using Phaseolus vulgaris leucoagglutinin (PHA-L) as anterograde tracer. The results show that the dorsolateral VTA projects to itself, as well as to the dorsal tier of the SNc and RR, largely avoiding the caudomedial VTA. The ventrolateral VTA innervates mainly the interfascicular nucleus. The components of the caudomedial VTA (the interfascicular, paranigral and caudal linear nuclei) are connected with each other. In addition, the caudomedial VTA (especially the paranigral and caudal linear nuclei) innervates the lateral VTA, and, to a lesser degree, the SNc and RR. The caudal pole of the VTA sends robust, bilateral projections to virtually all the VTA-nigral complex, which terminate in the dorsal and ventral tiers. Modest inputs from the medial supramammillary nucleus to ventromedial parts of the VTA-nigral complex were also identified. In double-immunostained sections, PHA-L-labeled varicosities were sometimes found apposed to tyrosine hydroxylase-positive neurons in the ventral mesencephalon. Overall, the results underscore that VTA projections to the VTA-nigral complex are substantial and topically organized. In general, these projections, like the spiralated striato-nigro-striatal loops, display a medial-to-lateral organization. This anatomical arrangement conceivably permits the ventromedial striatum to influence the activity of the lateral striatum. The caudal pole of the VTA appears to be a critical site for a global recruitment of the mesotelencephalic system.
Assuntos
Substância Negra/anatomia & histologia , Área Tegmentar Ventral/anatomia & histologia , Animais , Transporte Axonal/fisiologia , Mapeamento Encefálico , Dopamina/metabolismo , Feminino , Imuno-Histoquímica , Vias Neurais/anatomia & histologia , Vias Neurais/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Fito-Hemaglutininas , Terminações Pré-Sinápticas/metabolismo , Ratos , Ratos Wistar , Coloração e Rotulagem , Substância Negra/metabolismo , Tegmento Mesencefálico/anatomia & histologia , Tegmento Mesencefálico/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , Área Tegmentar Ventral/metabolismoRESUMO
INTRODUCTION: The pedunculopontine nucleus (PPN), co-localized with the mesencephalic locomotor region, has been proposed as a key structure in the physiopathology of Parkinson's disease. OBJECTIVES: The goal of the present study was to assess if the aminoacid neurotransmitter release in the PPN is modified by the degeneration of dopaminergic cells, from substantia nigra pars compacta in 6-hydroxidopamine (6-OHDA)-lesioned rats. In addition, it was studied the aminoacid neurotransmitter release in the PPN of rats with lesion of the subthalamic nucleus by quinolinic acid (QUIN) (100 nmol) intracerebral injection. MATERIALS AND METHODS: Rats were assigned to five groups: untreated rats (I) (n = 13), 6-OHDA lesion (II) (n = 11), 6-OHDA + QUIN lesion (III) (n = 9), sham-operated (IV) (n = 10), QUIN, STN (V) lesioned (n = 9). The extracellular concentrations of glutamic acid (GLU) and gamma-aminobutyric acid (GABA) were determined by brain microdialysis and high performance liquid chromatography (HPLC). RESULTS. GLU released in PPN from 6-OHDA lesioned rats (group II), was significantly increased in comparison with the others groups (F(4, 47) = 18.21, p < 0.001). GABA released shows significant differences between experimental groups (F(4, 45) = 12.75, p < 0.001). It was detected a higher valour (p < 0.05) in-group II. The groups III and IV exhibited intermeddle valour (p < 0.001) and groups I and IV (p < 0.001) showed the lower GABA extracellular concentrations. The infusion of artificial cerebrospinal fluid with higher potassium (100 mmol) induced an increase in the GLU and GABA released in all groups, which confirm the neuronal origin of the extracellular content. CONCLUSION: These results are in agreement with the current model of basal ganglia functioning and suggest the role of STN-PPN projection in the physiopathology of Parkinson's disease.
Assuntos
Ácido Glutâmico/metabolismo , Núcleo Tegmental Pedunculopontino/metabolismo , Substância Negra , Ácido gama-Aminobutírico/metabolismo , Adrenérgicos/farmacologia , Animais , Encéfalo/citologia , Encéfalo/metabolismo , Encéfalo/patologia , Química Encefálica , Dopamina/metabolismo , Ácido Glutâmico/química , Masculino , Microdiálise , Neurônios/citologia , Neurônios/metabolismo , Oxidopamina/farmacologia , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Núcleo Tegmental Pedunculopontino/citologia , Ratos , Ratos Wistar , Substância Negra/anatomia & histologia , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Substância Negra/patologia , Ácido gama-Aminobutírico/químicaRESUMO
The human dopamine D4 receptor (D4R) has received considerable attention because of its high affinity for the atypical antipsychotic clozapine and the unusually polymorphic nature of its gene. To clarify the in vivo role of the D4R, we produced and analyzed mutant mice (D4R-/-) lacking this protein. Although less active in open field tests, D4R-/- mice outperformed wild-type mice on the rotarod and displayed locomotor supersensitivity to ethanol, cocaine, and methamphetamine. Biochemical analyses revealed that dopamine synthesis and its conversion to DOPAC were elevated in the dorsal striatum from D4R-/- mice. Based on these findings, we propose that the D4R modulates normal, coordinated and drug-stimulated motor behaviors as well as the activity of nigrostriatal dopamine neurons.
Assuntos
Depressores do Sistema Nervoso Central/farmacologia , Cocaína/farmacologia , Dopaminérgicos/farmacologia , Etanol/farmacologia , Metanfetamina/farmacologia , Entorpecentes/farmacologia , Receptores de Dopamina D2/genética , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Sequência de Aminoácidos , Animais , Antipsicóticos/farmacologia , Comportamento Animal/efeitos dos fármacos , Clozapina/farmacologia , Corpo Estriado/anatomia & histologia , Corpo Estriado/química , Corpo Estriado/metabolismo , Dopamina/metabolismo , Genótipo , Humanos , Levodopa/análise , Levodopa/farmacocinética , Locomoção/efeitos dos fármacos , Comportamento Materno/efeitos dos fármacos , Camundongos , Camundongos Knockout , Dados de Sequência Molecular , Atividade Motora/efeitos dos fármacos , Mutagênese Sítio-Dirigida/fisiologia , Núcleo Accumbens/química , Núcleo Accumbens/metabolismo , Receptores de Dopamina D2/deficiência , Receptores de Dopamina D4 , Sensibilidade e Especificidade , Substância Negra/anatomia & histologia , Substância Negra/química , Substância Negra/metabolismo , Transcrição Gênica/genéticaRESUMO
Evaluation of the participation of different substantia nigra sites in the sensitization of resistant (R) animals to audiogenic seizures (AS), was performed after series of small (5 mC; n = 28), medium (10 mC; n = 57) and large (15 mC; 3 points of 5 mC each, n = 19) unilateral electrolytic lesions of the substantia nigra (SN) in R rats. Animals were evaluated at 5, 10, 15, and 30 days post surgery and behavior was measured by a neuroethological method. Small unilateral lesions induced AS susceptibility in 14% R animals with 3% of them displaying tonic-clonic AS. Medium sized lesions induced AS susceptibility in 50% of the animals with 18% of these exhibiting tonic-clonic seizures similar to those displayed by naturally susceptible (S) animals, but with predominance of wild running (gyri, jumping and atonic falling) contralateral to the lesioned SN. AS severity was significantly higher at day 5 postsurgery, decreasing at days 10, 15 and 30. Large unilateral lesions destroying the entire SN failed to cause tonic-clonic seizures although wild running occurred in 10% of the animals. Bilateral large SN lesions (15 mC; n = 24) did not modify AS severity in S animals, but only induced a statistically significant increase in the AS latency. The present data suggest: (i) AS severity after SN lesions is not a linear function of the lesion size; (ii) functionally different and antagonistic AS related substrates may exist in the SN; (iii) neurochemical and hodological characterization of these areas should be important for a better understanding of their role in AS.
Assuntos
Convulsões/fisiopatologia , Substância Negra/fisiologia , Estimulação Acústica , Animais , Comportamento Animal/fisiologia , Mapeamento Encefálico , Epilepsia Tônico-Clônica/fisiopatologia , Epilepsia Tônico-Clônica/psicologia , Masculino , Atividade Motora/fisiologia , Ratos , Ratos Wistar , Restrição Física , Convulsões/psicologia , Técnicas Estereotáxicas , Substância Negra/anatomia & histologiaRESUMO
Presentamos nuevos conceptos relativos a la etiología de la Enfermedad de Parkinson (EP). Basado en los hallazgos sobre la angio-arquitectura, relaciones neurono-vasculares y actividad metabólica de la zona compacta de la sustancia negra normal y parkinsoniana, nosotros creemos que una reducción subóptima en el flujo sanguíneo y su persistencia crónica a al sustancia negra, puede ser la clave en la patogénesis de la EP. Por el contrario, suponiendo que nuestra hipótesis es correcta, una revascularización de la sustancia negra podría detener o mejorar esta enfermedad.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Doença de Parkinson/etiologia , Substância Negra/lesões , Microcirculação/anormalidades , Substância Negra/anatomia & histologiaRESUMO
Substantia nigra (SN) is known to play an important role in seizure generalization. Both excitatory and inhibitory neurotransmitters can modulate this role of SN. Previous studies have shown that GABA as well as aspartate and glutamate participate in seizure regulation through this site. Evidence for such a role comes from studies on the genetically epilepsy-prone rat (GEPR) and other seizure models. In the GEPR, bilateral microinjections of NMDA receptor antagonists in SN block or reduce seizure severity. In order to further evaluate which neurotransmitters are specifically involved at the SN level of seizure regulation in the GEPR, we undertook a microdialysis study of K+ stimulated release of amino acids in the SN of GEPR-9s- and non-epileptic controls. A 1 mm loop-type microdialysis probe was inserted through pre-implanted guides into the SN of awake and freely moving rats (seven GEPR-9s and four non-epileptic controls), and used to perfuse a 100 mM K+ (high K+) solution for 2 h. Four 30 microliters samples were collected prior to high K+ stimulation (basal release), during high K+ perfusion, and after high K+ infusion. After precolumn derivatization with phenylisothiocyanate, levels of aspartic (ASP) and glutamic (GLU) acids, glycine (GLY), taurine (TAU) and GABA were measured by reversed phase high performance liquid chromatography. Two hours after the initiation of high K+ infusion, the increases relative to basal were, for non-epileptic controls, 35%, 74%, 68%, 847% and 283% respectively for ASP, GLU, GLY, TAU and GABA. Corresponding increases for GEPR-9s were 14%, 10%, 41%, 505% and 123% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Aminoácidos/metabolismo , Epilepsia/metabolismo , Espaço Extracelular/metabolismo , Convulsões/fisiopatologia , Substância Negra/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Epilepsia/genética , Masculino , Microdiálise , Potássio/farmacologia , Ratos , Ratos Endogâmicos , Espectrofotometria Ultravioleta , Substância Negra/anatomia & histologia , Taurina/metabolismoRESUMO
Midbrain tectum (MT) structures such as the dorsal periaqueductal gray matter and deep layers of superior colliculus are well-known for the organization and generation of defensive behaviour. Electrical stimulation or microinjection of GABA antagonists into these structures produce aversive behaviour. In order to determine whether the nigrocollicular GABAergic fibers exert some control over this behaviour, rats bearing neurochemical lesions with kainic acid in the substantia nigra, pars reticulata (SNpr) and compacta (SNpc), were submitted to MT microinjections of bicuculline or electrical stimulation at aversive thresholds. The same procedure was carried out after enhancement or inhibition of GABAergic transmission in SNpr through microinjections of muscimol or bicuculline, respectively. Animals with SNpr neurochemical lesion exhibited a significant decrease in the aversive thresholds and an increase in the responsiveness to bicuculline microinjections. An opposite effect was observed following microinjections of bicuculline into the SNpr. The enhancement of the GABAergic transmission into the SNpr following microinjection of muscimol mimicked the effects produced by the lesion with kainic acid. These results suggest an inhibitory control of GABAergic fibers from the substantia nigra, pars reticulata, on aversive behaviour induced by midbrain stimulation.
Assuntos
Agressão/fisiologia , Mesencéfalo/fisiologia , Substância Negra/fisiologia , Colículos Superiores/fisiologia , Ácido gama-Aminobutírico/fisiologia , Agressão/efeitos dos fármacos , Animais , Bicuculina/administração & dosagem , Bicuculina/farmacologia , Estimulação Elétrica , Reação de Fuga/efeitos dos fármacos , Antagonistas GABAérgicos , Ácido Caínico/administração & dosagem , Ácido Caínico/farmacologia , Masculino , Mesencéfalo/anatomia & histologia , Microinjeções , Muscimol/administração & dosagem , Muscimol/farmacologia , Fibras Nervosas/fisiologia , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Ratos , Ratos Wistar , Estimulação Química , Substância Negra/anatomia & histologia , Colículos Superiores/anatomia & histologiaRESUMO
Circumscribed lesions of the caudate nucleus were made in four cats and two kittens. A third kitten was lesioned in the Middle Forebrain Bundle (MFB). Cats were sacrificed 8 days after the lesion and perfused intraventricularly with 10 per cent Formalin. Kittens were sacrificed 3 days after the lesion. Coronal frozen sections of the brains were made and studied under the light microscope with the Fink and Heimer staining method. Degeneration was observed in the contralateral caudate nucleus, in the homo and contralateral putamen, in the globus pallidum and in the accumbens. The substantia nigra was intensely involved as well as the red nucleus and the mesencephalic reticular formation. Patches of degeneration were also found in the superior colliculus and in the thalamus. As a preliminary conclusion we think that the projection of the caudate reaches all those structures by the middle forebrain bundle. The degeneration of the contralateral areas could be explained through a path of the anterior commissure.