RESUMO
The lateral habenula (LHb) is an epithalamic structure differentiated in a medial (LHbM) and a lateral division (LHbL). Together with the rostromedial tegmental nucleus (RMTg), the LHb has been implicated in the processing of aversive stimuli and inhibitory control of monoamine nuclei. The inhibitory LHb influence on midbrain dopamine neurons has been shown to be mainly mediated by the RMTg, a mostly GABAergic nucleus that receives a dominant input from the LHbL. Interestingly, the RMTg also projects to the dorsal raphe nucleus (DR), which also receives direct LHb projections. To compare the organization and transmitter phenotype of LHb projections to the DR, direct and indirect via the RMTg, we first placed injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin into the LHb or the RMTg. We then confirmed our findings by retrograde tracing and investigated a possible GABAergic phenotype of DR-projecting RMTg neurons by combining retrograde tracing with in situ hybridization for GAD67. We found only moderate direct LHb projections to the DR, which mainly emerged from the LHbM and were predominantly directed to the serotonin-rich caudal DR. In contrast, RMTg projections to the DR were more robust, emerged from RMTg neurons enriched in GAD67 mRNA, and were focally directed to a distinctive DR subdivision immunohistochemically characterized as poor in serotonin and enriched in presumptive glutamatergic neurons. Thus, besides its well-acknowledged role as a GABAergic control center for the ventral tegmental area (VTA)-nigra complex, our findings indicate that the RMTg is also a major GABAergic relay between the LHb and the DR.
Assuntos
Habenula/anatomia & histologia , Neurônios/citologia , Núcleos da Rafe/anatomia & histologia , Tegmento Mesencefálico/anatomia & histologia , Animais , Imunofluorescência , Habenula/metabolismo , Técnicas Imunoenzimáticas , Imuno-Histoquímica , Masculino , Vias Neurais/anatomia & histologia , Vias Neurais/metabolismo , Técnicas de Rastreamento Neuroanatômico , Neurônios/metabolismo , Núcleos da Rafe/metabolismo , Ratos , Ratos Wistar , Neurônios Serotoninérgicos/citologia , Neurônios Serotoninérgicos/metabolismo , Serotonina/metabolismo , Tegmento Mesencefálico/metabolismo , Proteínas Vesiculares de Transporte de Glutamato/metabolismo , Ácido gama-Aminobutírico/metabolismoRESUMO
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
Striatal activation can modify activity in cortical areas related to specific striatal functions possibly through a process of disinhibition within the basal ganglia. Anatomical studies have shown substantial GABAergic innervation from these nuclei to the pedunculopontine tegmental nucleus (PPT). Thus, dopaminergic stimulation of the striatum could produce PPT disinhibition and result in non-specific cortical activation. To test this hypothesis, d-amphetamine was infused both into the striatum of freely moving rats for motor and electrocorticographic recordings, and into the striatum of animals under deep anesthesia for c-Fos immunohistochemistry. The results show that intrastriatal amphetamine increases wakefulness independent of motor activity, and it increases c-Fos expression in the PPT and adjacent areas. They also suggest that the striatum participates in non-specific cortical activation probably as a result of its relationship with the PPT.
Assuntos
Corpo Estriado/metabolismo , Dopamina/metabolismo , Vias Neurais/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Tegmento Mesencefálico/metabolismo , Vigília/fisiologia , Animais , Doenças dos Gânglios da Base/complicações , Fibras Colinérgicas/metabolismo , Corpo Estriado/citologia , Corpo Estriado/efeitos dos fármacos , Dextroanfetamina/farmacologia , Globo Pálido/citologia , Globo Pálido/efeitos dos fármacos , Globo Pálido/metabolismo , Masculino , Neostriado/citologia , Neostriado/efeitos dos fármacos , Neostriado/metabolismo , Inibição Neural/efeitos dos fármacos , Inibição Neural/fisiologia , Vias Neurais/citologia , Vias Neurais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/metabolismo , Transtornos do Sono-Vigília/fisiopatologia , Tegmento Mesencefálico/citologia , Tegmento Mesencefálico/efeitos dos fármacos , Vigília/efeitos dos fármacosRESUMO
Using immunocytochemistry we have described the distribution and ontogeny of three distinct gonadotropin-releasing hormone (GnRH) neural systems, emphasizing the analysis during the period of sex differentiation in the South American cichlid fish Cichlasoma dimerus. In the forebrain a group of neurones immunoreactive to salmon GnRH that formed clusters in the nucleus olfacto retinalis (NOR), was located at the junction of the olfactory bulb and the telencephalon. These neurones differentiated 3 days after fertilization from the olfactory placodes. GnRH immunoreactive neurones along the olfactory nerves through the rostrobasal olfactory bulb were observed on day 4 and at the NOR on day 10. A group of neurones immunoreactive to chicken GnRH II was seen in the dorsal midbrain tegmentum. They originate from the ventricular ependyma between days 5 and 6. These neurones remained close to blood vessels throughout development. Between days 22 and 30 a group of neurones immunoreactive to seabream GnRH was detected in the anterior basal preoptic area. GnRH innervation of the pituitary was detected after the differentiation of preoptic neurones and in coincidence with gonadal differentiation. We hypothesize that the GnRH neural systems have three distinct embryonic origins. Furthermore, we show that the NOR and the midbrain GnRH neurones might have functions other than gonadal development, whereas the preoptic GnRH neurones in C. dimerus might be associated with gonadal sex differentiation.