RESUMO
The dorsomedial nucleus of the hypothalamus (DMH) is part of the brain circuits that modulate organism responses to the circadian cycle, energy balance, and psychological stress. A large group of thyrotropin-releasing hormone (Trh) neurons is localized in the DMH; they comprise about one third of the DMH neurons that project to the lateral hypothalamus area (LH). We tested their response to various paradigms. In male Wistar rats, food restriction during adulthood, or chronic variable stress (CVS) during adolescence down-regulated adult DMH Trh mRNA levels compared to those in sedentary animals fed ad libitum; two weeks of voluntary wheel running during adulthood enhanced DMH Trh mRNA levels compared to pair-fed rats. Except for their magnitude, female responses to exercise were like those in male rats; in contrast, in female rats CVS did not change DMH Trh mRNA levels. A very strong negative correlation between DMH Trh mRNA levels and serum corticosterone concentration in rats of either sex was lost in CVS rats. CVS canceled the response to food restriction, but not that to exercise in either sex. TRH receptor 1 (Trhr) cells were numerous along the rostro-caudal extent of the medial LH. In either sex, fasting during adulthood reduced DMH Trh mRNA levels, and increased LH Trhr mRNA levels, suggesting fasting may inhibit the activity of TRHDMH->LH neurons. Thus, in Wistar rats DMH Trh mRNA levels are regulated by negative energy balance, exercise and chronic variable stress through sex-dependent and -independent pathways.
Assuntos
Hipotálamo , Hormônio Liberador de Tireotropina , Animais , Feminino , Masculino , Ratos , Corticosterona , Hipotálamo/metabolismo , Núcleo Mediodorsal do Tálamo , Atividade Motora , Ratos Wistar , Receptores do Hormônio Liberador da Tireotropina/genética , Receptores do Hormônio Liberador da Tireotropina/metabolismo , RNA Mensageiro/metabolismo , Hormônio Liberador de Tireotropina/genética , Hormônio Liberador de Tireotropina/metabolismoRESUMO
The thalamus is a deep cerebral structure that is crucial for proper neurological functioning as it transmits signals from nearly all pathways in the body. Insult to the thalamus can, therefore, result in complex syndromes involving sensation, cognition, executive function, fine motor control, emotion, and arousal, to name a few. Specific territories in the thalamus that are supplied by deep cerebral arteries have been shown to correlate with clinical symptoms. The aim of this review is to enhance our understanding of the arterial anatomy of the thalamus and the complications that can arise from lesions to it by considering the functions of known thalamic nuclei supplied by each vascular territory.
Assuntos
Artéria Basilar/anatomia & histologia , Infarto Encefálico/fisiopatologia , Círculo Arterial do Cérebro/anatomia & histologia , Artéria Cerebral Posterior/anatomia & histologia , Tálamo/irrigação sanguínea , Núcleos Anteriores do Tálamo/anatomia & histologia , Núcleos Anteriores do Tálamo/irrigação sanguínea , Núcleos Anteriores do Tálamo/fisiologia , Corpos Geniculados/anatomia & histologia , Corpos Geniculados/irrigação sanguínea , Corpos Geniculados/fisiologia , Humanos , Núcleos Laterais do Tálamo/anatomia & histologia , Núcleos Laterais do Tálamo/irrigação sanguínea , Núcleos Laterais do Tálamo/fisiologia , Núcleo Mediodorsal do Tálamo/anatomia & histologia , Núcleo Mediodorsal do Tálamo/irrigação sanguínea , Núcleo Mediodorsal do Tálamo/fisiologia , Pulvinar/anatomia & histologia , Pulvinar/irrigação sanguínea , Pulvinar/fisiologia , Tálamo/anatomia & histologia , Tálamo/fisiologia , Núcleos Ventrais do Tálamo/anatomia & histologia , Núcleos Ventrais do Tálamo/irrigação sanguínea , Núcleos Ventrais do Tálamo/fisiologiaRESUMO
The dorsal raphe nucleus (DR), the main source of 5-HT projections to brain areas involved in anxiety regulation, is composed by 5 subnuclei that differ morphologically, functionally and neurochemically. Based on immunohistochemical evidence, it has been proposed that whereas 5-HT cells of the dorsomedial (dmDR) and caudal subnuclei are implicated in the pathophysiology of generalized anxiety disorder (GAD), neurons of the lateral wings (lwDR) are associated with panic disorder (PD). We here tested this hypothesis from a behavioral perspective by investigating the consequences of the non-selective stimulation of neurons within the dmDR and lwDR, or the pharmacological manipulation of 5-HT1A receptors located in these nuclei, of male Wistar rats exposed to the elevated T-maze. This test allows the measurement of both a GAD- (i.e. inhibitory avoidance) and a PD- (i.e. escape) related response in the same animal. Intra-dmDR injection of either the excitatory amino acid kainic acid or the 5-HT1A receptor antagonist WAY-100635 facilitated inhibitory avoidance acquisition, suggesting an anxiogenic effect, and inhibited escape expression, a panicolytic-like effect. Microinjection of the 5-HT1A receptor agonist 8-OH-DPAT caused the opposite effect. Administration of the same drugs into the lwDR only altered escape performance. Whereas kainic acid and 8-OH-DPAT facilitated its expression, WAY-100635 inhibited it. At higher doses, kainic acid administration evoked vigorous escape reactions as measured in an open-field. These findings implicate 5-HT neurons of the dmDR in the regulation of both GAD- and PD-related defensive behaviors. They also support a primary role of the lwDR in the mediation of PD-associated responses.
Assuntos
Ansiedade/metabolismo , Núcleo Dorsal da Rafe/metabolismo , Núcleo Mediodorsal do Tálamo/metabolismo , Pânico/fisiologia , Receptor 5-HT1A de Serotonina/metabolismo , Neurônios Serotoninérgicos/metabolismo , Animais , Núcleo Dorsal da Rafe/efeitos dos fármacos , Reação de Fuga/efeitos dos fármacos , Reação de Fuga/fisiologia , Masculino , Núcleo Mediodorsal do Tálamo/efeitos dos fármacos , Pânico/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Wistar , Neurônios Serotoninérgicos/efeitos dos fármacos , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , Antagonistas do Receptor 5-HT1 de Serotonina/farmacologiaRESUMO
The mediodorsal thalamic nucleus is a prominent nucleus in the thalamus, positioned lateral to the midline nuclei and medial to the intralaminar thalamic complex in the dorsal thalamus. Several studies identify the mediodorsal thalamic nucleus as a key structure in learning and memory, as well as in emotional mechanisms and alertness due to reciprocal connections with the limbic system and prefrontal cortex. Fibers from the retina to the mediodorsal thalamic nucleus have recently been described for the first time in a crepuscular rodent, suggesting a possible regulation of the mediodorsal thalamic nucleus by visual activity. The present study shows retinal afferents in the mediodorsal thalamic nucleus of a new world primate, the marmoset (Callithrix jacchus), using B subunit of cholera toxin (CTb) as an anterograde tracer. A small population of labeled retinofugal axonal arborizations is consistently labeled in small domains of the medial and lateral periphery of the caudal half of the mediodorsal nucleus. Retinal projections in the mediodorsal thalamic nucleus are exclusively contralateral and the morphology of the afferent endings was examined. Although the functional significance of this projection remains unknown, this retina-mediodorsal thalamic nucleus pathway may be involved in a wide possibility of functional implications.
Assuntos
Toxina da Cólera , Núcleo Mediodorsal do Tálamo/anatomia & histologia , Núcleo Mediodorsal do Tálamo/fisiologia , Retina/anatomia & histologia , Retina/fisiologia , Vias Visuais/anatomia & histologia , Vias Visuais/fisiologia , Animais , Axônios/fisiologia , Callithrix , Imuno-Histoquímica , Masculino , MicrotomiaRESUMO
The present study explored the effects of early and post-weaning malnutrition and nutritional rehabilitation on orexigenic (orexin (ORX) and neuropeptide Y (NPY)) and anorexigenic peptides (alpha-melanocyte stimulating hormone (alpha-MSH)) expressed in hypothalamic nuclei. Male Wistar rats were malnourished during gestation-lactation (MGL) or from weaning to post-natal day 55 (MPW; P55). Two groups of rats were rehabilitated with a balanced diet until P90 (MGL-R and MPW-R, respectively). After a glucose tolerance test (GTT) brains were processed for immunohistochemistry. Malnourished groups were hyperglycemic after GTT. ORX expression did not display any difference. Only MGL rats showed increased NPY immunoreactivity in ARC and PVN nuclei, and both malnourished groups showed low alpha-MSH expression in the PVN and DMH, as compared with their controls. After nutritional rehabilitation rats showed normal GTT, increased rate of body and adipose tissue weights and high proportion of food ingestion. Both rehabilitated groups maintained low alpha-MSH expression in the PVN, indicating a deleterious long-lasting effect.
Assuntos
Hipotálamo/fisiopatologia , Desnutrição/fisiopatologia , Sobrepeso/fisiopatologia , alfa-MSH/metabolismo , Animais , Feminino , Teste de Tolerância a Glucose , Hiperglicemia/fisiopatologia , Hipotálamo/citologia , Imuno-Histoquímica/métodos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Lactação , Masculino , Núcleo Mediodorsal do Tálamo/fisiopatologia , Neurônios/citologia , Neurônios/metabolismo , Neuropeptídeo Y/metabolismo , Neuropeptídeos/metabolismo , Orexinas , Ratos , Ratos Wistar , DesmameRESUMO
The MD has reciprocal connections with the ventromedial prefrontal cortex (PFC) and with limbic cortices and appears to participate in learning and memory-related processes. In this study, we report the identification of a hitherto not reported direct retinal projection to the MD of the rock cavy, a typical rodent species of the Northeast region of Brazil. After unilateral intravitreal injections of cholera toxin subunit B (CTb), anterogradely transported CTb-imunoreactive fibers and presumptive terminals were seen in the MD. A few labeled retinal fibers/terminals detected in the MD of the rock cavy brain show clear varicosities, suggesting terminal fields. The present work is the first to show a direct retinal projection to the MD of rodents and may contribute for elucidating the anatomical substrate of the functional involvement of this thalamic nucleus in the modulation of the visual recognition, emotional learning and object-reward association memory.
Assuntos
Núcleo Mediodorsal do Tálamo/fisiologia , Retina/fisiologia , Vias Visuais , Animais , Masculino , RoedoresRESUMO
A amígdala, a substância cinzenta periaquedutal dorsal (SCPd) e o hipotálamo medial são reconhecidos há muito tempo como um circuito neural responsável pela geração e elaboração do medo incondicionado, designado como sistema encefálico aversivo. É bem estabelecido que esse sistema neural encontra-se sobre controle inibitório tônico exercido por mecanismos gabaérgicos. Todavia, enquanto uma quantidade apreciável de evidências sugerem que tanto a amígdala quanto a SCPd participam também da integração do medo condicionado, ainda não está claro a participação dos distintos núcleos hipotalâmicos nesse tipo de condicionamento. Portanto, o presente trabalho destinou-se a avaliar, através do modelo do sobressalto potencializado pelo medo (SPM), se mecanismos gabaérgicos da região hipotalâmica de defesa estão envolvidos na mediação de respostas aversivas condicionadas. Muscimol, agonista de receptor GABAA e semicarbazida, inibidor da síntese de descarboxilase do ácido glutâmico (DAG -enzima responsável pela síntese de GABA) foram utilizados como facilitador ou inibidor de mecanismos gabaérgicos, respectivamente. Essas drogas foram injetadas no núcleo hipotalâmico anterior (HA), na porção dorsomedial do núcleo ventromedial (HVMDM), nos núcleos dorsomedial (HDM) ou pré-mamilar dorsal (PMD) de ratos Wistar machos, antes da sessão teste do SPM. Essas regiões constituem o sistema defensivo hipotalâmico. Tanto as injeções de muscimol quanto de semicarbazida administradas no HDM ou no PMD não produziram qualquer efeito significativo sobre as respostas de SPM. Por outro lado, injeções de muscimol no HA e no HVMDM promoveram reduções significativas dessas respostas. Esses resultados mostram que, enquanto o aumento ou a diminuição da neurotransmissão gabaérgica no HDM e no PMD não influenciam as respostas de SPM, o aumento dessa neurotransmissão no HA e HVMDM diminui a expressão das respostas aversivas condicionadas...(AU)
The amygdala, the dorsal periaqueductal gray (dPAG) and the medial hypothalamus have long been recognized to be a neural system responsible for the generation and elaboration of unconditioned fear in the brain. It is algo well known that this neural substrate is under a tonic inhibitory contraI exerted by GABA mechanisms. Nevertheless, whereas there is a growing body of evidence to suggest that the amygdala and dP AG are algo able to integrate conditioned fear, it is still unclear, however, how the distinct hypothalamic nuclei participate in fear conditioning. In this work, we aimed to examine the extent to which the gabaergic mechanisms of this brain region are involved in conditioned fear using the fear- potentiated startle (FPS). Muscimol, a GABA-A receptor agonist, and semicarbazide, an inhibitor of the GABA synthetisizing enzyme glutamic acid decarboxylase (GAD), were used as an enhancer and inhibitor of the GABA mechanisms, respectively. Muscimol and semicarbazide were injected into the anterior hypothalamus (AHN), the dorsomedial part of the ventromedial nucleus (VMHDM), the dorsomedial (DMH) or the dorsal premammillary (PMD) nuclei of male Wistar rats before test sessions of the fear conditioning paradigm. The injections into the DMH and PMD did not produce any significant effects on FPS. On the other hand, muscimol injections into the AHN and VMHDM caused significant reduction in FPS. These results indicate that injections of muscimol and semicarbazide into the DMH and PMD fail to change the FPS, whereas the enhancement of the GABA transmission in the AHN and VMHDM produces a reduction of the conditioned fear responses. At the same time, the inhibition of this transmission led to an increase of this conditioned response in the AHN. Thus, whereas DMH and PMD are known to be part of the caudal-most region of the medial hypothalamic defensive system, which integrates unconditioned fear, systems ...(AU)
Assuntos
Animais , Ratos , Núcleo Hipotalâmico Anterior , Núcleo Mediodorsal do Tálamo , Núcleos Ventrais do Tálamo , Ácido gama-AminobutíricoRESUMO
The dorsal (DRN) and median (MRN) raphe nuclei are important sources of serotonergic innervation to the forebrain, projecting to sites involved in cardiovascular regulation. These nuclei have been mapped using electrical stimulation, which has the limitation of stimulating fibers of passage. The present study maps these areas with chemical stimulation, investigating their influence on cardiorespiratory parameters. Urethane-anesthetized (1.2 g/kg, iv) male Wistar rats (280-300 g) were instrumented for pulsatile and mean blood pressure (MBP), heart rate, renal nerve activity, and respiratory frequency recordings. Microinjections of L-glutamate (0.18 M, 50-100 nl with 1% Pontamine Sky Blue) were performed within the DRN or the MRN with glass micropipettes. At the end of the experiments the sites of microinjection were identified. The majority of sites within the MRN (86.1%) and DRN (85.4%) evoked pressor responses when stimulated (DRN: DeltaMBP = +14.7 +/- 1.2; MRN: DeltaMBP = +13.6 +/- 1.3 mmHg). The changes in renal nerve activity and respiratory rate caused by L-glutamate were +45 +/- 11 and +42 +/- 9% (DRN; P < 0.05%), +40 +/- 10 and +29 +/- 7% (MRN, P < 0.05), respectively. No significant changes were observed in saline-microinjected animals. This study shows that: a) the blood pressure increases previously observed by electrical stimulation within the raphe are due to activation of local neurons, b) this pressor effect is due to sympathoexcitation because the stimulation increased renal sympathetic activity but did not produce tachycardia, and c) the stimulation of cell bodies in these nuclei also increases the respiratory rate.
Assuntos
Mapeamento Encefálico , Ácido Glutâmico/farmacologia , Núcleo Mediodorsal do Tálamo/fisiologia , Neurônios/efeitos dos fármacos , Núcleos da Rafe/fisiologia , Animais , Pressão Sanguínea/fisiologia , Estimulação Elétrica , Frequência Cardíaca/fisiologia , Masculino , Núcleo Mediodorsal do Tálamo/citologia , Núcleos da Rafe/citologia , Ratos , Ratos Wistar , Mecânica Respiratória/fisiologiaRESUMO
The dorsal (DRN) and median (MRN) raphe nuclei are important sources of serotonergic innervation to the forebrain, projecting to sites involved in cardiovascular regulation. These nuclei have been mapped using electrical stimulation, which has the limitation of stimulating fibers of passage. The present study maps these areas with chemical stimulation, investigating their influence on cardiorespiratory parameters. Urethane-anesthetized (1.2 g/kg, iv) male Wistar rats (280-300 g) were instrumented for pulsatile and mean blood pressure (MBP), heart rate, renal nerve activity, and respiratory frequency recordings. Microinjections of L-glutamate (0.18 M, 50-100 nl with 1 percent Pontamine Sky Blue) were performed within the DRN or the MRN with glass micropipettes. At the end of the experiments the sites of microinjection were identified. The majority of sites within the MRN (86.1 percent) and DRN (85.4 percent) evoked pressor responses when stimulated (DRN: deltaMBP = +14.7 ± 1.2; MRN: deltaMBP = +13.6 ± 1.3 mmHg). The changes in renal nerve activity and respiratory rate caused by L-glutamate were +45 ± 11 and +42 ± 9 percent (DRN; P < 0.05 percent), +40 ± 10 and +29 ± 7 percent (MRN, P < 0.05), respectively. No significant changes were observed in saline-microinjected animals. This study shows that: a) the blood pressure increases previously observed by electrical stimulation within the raphe are due to activation of local neurons, b) this pressor effect is due to sympathoexcitation because the stimulation increased renal sympathetic activity but did not produce tachycardia, and c) the stimulation of cell bodies in these nuclei also increases the respiratory rate.
Assuntos
Animais , Masculino , Ratos , Ácido Glutâmico/farmacologia , Mapeamento Encefálico , Neurônios/efeitos dos fármacos , Núcleo Mediodorsal do Tálamo/fisiologia , Núcleos da Rafe/fisiologia , Estimulação Elétrica , Frequência Cardíaca/fisiologia , Mecânica Respiratória/fisiologia , Núcleo Mediodorsal do Tálamo/citologia , Núcleos da Rafe/citologia , Pressão Arterial/fisiologia , Ratos WistarRESUMO
The postnatal development of mediodorsal thalamic projections to the dorsomedial frontal cortex of mice was assessed by means of the retrograde peroxidase-colloidal gold complex tract tracing system. The tracer was injected into the dorsomedial frontal cortex from the day of birth (P0) to 60 days of postnatal age (P60). Since birth, a dense retrograde labeling has been found in the mediodorsal nucleus, which increased progressively from P4 to P8 and began to decrease at P10 until P13 (67.37% vs. the maximal average, P4). After P16, the mean average remains stable up to P60.
Assuntos
Vias Aferentes/crescimento & desenvolvimento , Diferenciação Celular/fisiologia , Núcleo Mediodorsal do Tálamo/crescimento & desenvolvimento , Neurônios/citologia , Córtex Pré-Frontal/crescimento & desenvolvimento , Vias Aferentes/citologia , Envelhecimento/fisiologia , Animais , Animais Recém-Nascidos , Coloide de Ouro , Núcleo Mediodorsal do Tálamo/citologia , Camundongos , Córtex Pré-Frontal/citologia , Conjugado Aglutinina do Germe de Trigo-Peroxidase do Rábano SilvestreRESUMO
The role played by the serotoninergic system in the control of puberty onset and first ovulation in rats is studied in this paper by analyzing the effects of injecting the neurotoxin 5,6-dihydroxytryptamine (5,6-DHT) into the dorsal (DRN) or medial (MRN) raphe nucleus of 30-day-old female rats. Complete lesion to the DRN resulted in the blockade of ovulation and a decrease in both the number of ovarian follicles and the serum concentration of follicle stimulating hormone (FSH). This treatment was also found to be associated with an increase in serotoninergic activity in the anterior and medial hypothalami. A lesion to the central portion of the DRN resulted in a significant decrease in the concentration of progesterone in serum and in the number of ova shed by ovulating animals. The lesion to the lateral portion of the DRN did not have an apparent effect on ovulation rate, the number of ova shed, nor in hormone serum concentration. The injection of propranolol to rats with a lesion to the DRN restored ovulation in 73% of treated animals and returned serotoninergic activity in the anterior hypothalamus to levels similar to those of sham-operated animals. In turn, in the medial hypothalamus, the increase in serotoninergic activity was not modified. The results presented herein suggest that serotoninergic inputs to the anterior hypothalamus have a direct influence on gonadotropin secretion and first ovulation, while the noradrenergic innervation exerts an indirect influence.