RESUMO
Methamphetamine (Meth) seeking progressively increases after cessation from drug self-administration (incubation of Meth craving). We have previously shown that both dorsomedial and dorsolateral striatum (DMS and DLS) play critical roles in this incubation in male rats. Moreover, our recent anatomical tracing study examined afferent projections into DMS and demonstrated a novel role of projections from anterior intralaminar nucleus of thalamus (AIT) to DMS in incubation of Meth craving in male rats. Here we investigated projection-specific activation of afferent glutamate projections into DLS associated with incubated Meth seeking in female rats. We trained female rats to self-administer Meth (6-h/d for 10 d). On abstinence day 12, we injected cholera toxin subunit B (CTb, a retrograde tracer) unilaterally into DLS. On abstinence day 26, we tested rats for relapse to Meth seeking and measured Fos (a neuronal activity marker), and double-labeling of CTb and Fos in anterior cingulate cortex, anterior insula cortex, orbitofrontal cortex, basolateral amygdala, AIT, and parafascicular nuclei of thalamus. We observed neuronal activation in both cortical and thalamic regions associated with incubated Meth seeking. At the circuit level, AITâDLS projections were strongly activated, followed by other corticostriatal projections. Overall our results suggest that AIT to DLS may play a role in Meth seeking after prolonged abstinence in female rats.
Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Corpo Estriado/metabolismo , Comportamento de Procura de Droga/efeitos dos fármacos , Núcleos Intralaminares do Tálamo/metabolismo , Metanfetamina/farmacologia , Transtornos Relacionados ao Uso de Anfetaminas/metabolismo , Animais , Córtex Cerebral/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Fissura/efeitos dos fármacos , Feminino , Núcleos Intralaminares do Tálamo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Autoadministração/métodos , Tálamo/efeitos dos fármacos , Tálamo/metabolismoRESUMO
Non-competitive N-methyl-d-aspartate receptor antagonists mimic schizophrenia symptoms and produce immediate and persistent antidepressant effects. We investigated the effects of ketamine and phencyclidine (PCP) on thalamo-cortical network activity in awake, freely-moving male Wistar rats to gain new insight into the neuronal populations and brain circuits involved in the effects of NMDA-R antagonists. Single unit and local field potential (LFP) recordings were conducted in mediodorsal/centromedial thalamus and in medial prefrontal cortex (mPFC) using microelectrode arrays. Ketamine and PCP moderately increased the discharge rates of principal neurons in both areas while not attenuating the discharge of mPFC GABAergic interneurons. They also strongly affected LFP activity, reducing beta power and increasing that of gamma and high-frequency oscillation bands. These effects were short-lasting following the rapid pharmacokinetic profile of the drugs, and consequently were not present at 24â¯h after ketamine administration. The temporal profile of both drugs was remarkably different, with ketamine effects peaking earlier than PCP effects. Although this study is compatible with the glutamate hypothesis for fast-acting antidepressant action, it does not support a local disinhibition mechanism as the source for the increased pyramidal neuron activity in mPFC. The short-lasting increase in thalamo-cortical activity is likely associated with the rapid psychotomimetic action of both agents but could also be part of a cascade of events ultimately leading to the persistent antidepressant effects of ketamine. Changes in spectral contents of high-frequency bands by the drugs show potential as translational biomarkers for target engagement of NMDA-R modulators.
Assuntos
Potenciais de Ação/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Neurônios GABAérgicos/efeitos dos fármacos , Núcleos Intralaminares do Tálamo/efeitos dos fármacos , Ketamina/farmacologia , Núcleo Mediodorsal do Tálamo/efeitos dos fármacos , Fenciclidina/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Animais , Neurônios GABAérgicos/metabolismo , Interneurônios/efeitos dos fármacos , Interneurônios/metabolismo , Núcleos Intralaminares do Tálamo/citologia , Núcleos Intralaminares do Tálamo/metabolismo , Núcleo Mediodorsal do Tálamo/citologia , Núcleo Mediodorsal do Tálamo/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/metabolismo , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Tálamo , VigíliaRESUMO
The thalamic reticular nucleus (TRN), a cluster of GABAergic cells, is thought to regulate bottom-up and top-down streams of sensory processing in the loop circuitry between the thalamus and cortex. Provided that sensory inputs of different modalities interact in the TRN, the TRN could contribute to fast and flexible cross-modal modulation of attention and perception that incessantly takes place in our everyday life. Indeed, diverse subthreshold interactions of auditory and visual inputs have been revealed in TRN cells (Kimura, 2014). To determine whether such sensory interaction could extend across modalities as a universal neural mechanism, the present study examined TRN cell activities elicited by auditory and cutaneous electrical stimulations in anesthetized rats. Juxta-cellular recording and labeling techniques were used. Recordings were obtained from 129 cells. Auditory or somatosensory responses were modulated by subthreshold electrical stimulation or sound (noise burst) in the majority of recordings (77 of 85 auditory and 13 of 15 somatosensory cells). Additionally, 22 bimodal cells and seven cells that responded only to combined stimulation were recognized. Suppression was predominant in modulation that was observed in both early and repeatedly evoked late responses. Combined stimulation also induced de novo cell activities. Further, response latency and burst spiking were modulated. Axonal projections of cells showing modulation terminated in first- or higher-order thalamic nuclei. Nine auditory cells projected to somatosensory thalamic nuclei. These results suggest that the TRN could regulate sensory processing in the loop circuitry between the thalamus and cortex through the sensory interaction pervasive across modalities.
Assuntos
Vias Auditivas/fisiologia , Núcleos Intralaminares do Tálamo/metabolismo , Núcleos Intralaminares do Tálamo/fisiologia , Estimulação Acústica , Animais , Atenção/fisiologia , Percepção Auditiva/fisiologia , Axônios/fisiologia , Córtex Cerebral/fisiologia , Estimulação Elétrica , Corpos Geniculados/fisiologia , Masculino , Neurônios/fisiologia , Ratos , Ratos Wistar , Pele , Núcleos Talâmicos/fisiologia , Tálamo/metabolismo , Tálamo/fisiologia , Estimulação Elétrica Nervosa TranscutâneaRESUMO
T-type calcium channels (Cav3) are key mediators of thalamic bursting activity, but also regulate single cells excitability, dendritic integration, synaptic strength and transmitter release. These functions are strongly influenced by the subcellular and subsynaptic localization of Cav3 channels along the somatodendritic domain of thalamic cells. In Parkinson's disease, T-type calcium channels dysfunction in the basal ganglia-receiving thalamic nuclei likely contributes to pathological thalamic bursting activity. In this study, we analyzed the cellular, subcellular, and subsynaptic localization of the Cav3.1 channel in the ventral anterior (VA) and centromedian/parafascicular (CM/Pf) thalamic nuclei, the main thalamic targets of basal ganglia output, in normal and parkinsonian monkeys. All thalamic nuclei displayed strong Cav3.1 neuropil immunoreactivity, although the intensity of immunolabeling in CM/Pf was significantly lower than in VA. Ultrastructurally, 70-80 % of the Cav3.1-immunoreactive structures were dendritic shafts. Using immunogold labeling, Cav3.1 was commonly found perisynaptic to asymmetric and symmetric axo-dendritic synapses, suggesting a role of Cav3.1 in regulating excitatory and inhibitory neurotransmission. Significant labeling was also found at non-synaptic sites along the plasma membrane of thalamic neurons. There was no difference in the overall pattern and intensity of immunostaining between normal and parkinsonian monkeys, suggesting that the increased rebound bursting in the parkinsonian state is not driven by changes in Cav3.1 expression. Thus, T-type calcium channels are located to subserve neuronal bursting, but also regulate glutamatergic and non-glutamatergic transmission along the whole somatodendritic domain of basal ganglia-receiving neurons of the primate thalamus.
Assuntos
Canais de Cálcio Tipo T/metabolismo , Neurônios/metabolismo , Doença de Parkinson/metabolismo , Sinapses/metabolismo , Tálamo/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Núcleos Intralaminares do Tálamo/metabolismo , Núcleos Intralaminares do Tálamo/ultraestrutura , Macaca mulatta , Neurônios/ultraestrutura , Transtornos Parkinsonianos/metabolismo , Sinapses/ultraestrutura , Tálamo/ultraestrutura , Núcleos Ventrais do Tálamo/metabolismo , Núcleos Ventrais do Tálamo/ultraestruturaRESUMO
Although the intralaminar thalamus is a target of alpha-synuclein pathology in Parkinson's disease, the degree of neuronal loss in Lewy body diseases has not been assessed. We have used unbiased stereological techniques to quantify neuronal loss in intralaminar thalamic nuclei concentrating alpha-synuclein pathology (the anterodorsal, cucullar, parataenial, paraventricular, central medial, central lateral and centre-median/parafascicular complex) in different clinical forms of Lewy body disease (Parkinson's disease with and without dementia, and dementia with Lewy bodies, N=21) compared with controls (N=5). Associations were performed in the Lewy body cases between intralaminar cell loss and the main diagnostic clinical (parkinsonism, dementia, fluctuation in consciousness, and visual hallucinations) and pathological (Braak stage of Parkinson's disease) features of these diseases, as well as between cell loss and the scaled severity of the alpha-synuclein deposition within the intralaminar thalamus. As expected, significant alpha-synuclein accumulation occurred in the intralaminar thalamus in the cases with Lewy body disease. Pathology concentrated anteriorly and in the central lateral and paraventricular nuclei was related to the Braak stage of Parkinson's disease, ageing, and the presence of dementia. Across all types of Lewy body cases there was substantial atrophy and neuronal loss in the central lateral, cucullar and parataenial nuclei, and neuronal loss without atrophy in the centre-median/parafascicular complex. Cases with visual hallucinations showed a greater degree of atrophy of the cucullar nucleus, possibly due to amygdala denervation. The significant degeneration demonstrated in the intralaminar thalamus is likely to contribute to the movement and cognitive dysfunction observed in Lewy body disorders.
Assuntos
Núcleos Intralaminares do Tálamo/patologia , Doença por Corpos de Lewy/patologia , Tálamo/patologia , Idoso , Idoso de 80 Anos ou mais , Atrofia , Contagem de Células , Demência/patologia , Demência/fisiopatologia , Feminino , Alucinações/patologia , Alucinações/fisiopatologia , Humanos , Núcleos Intralaminares do Tálamo/metabolismo , Núcleos Intralaminares do Tálamo/fisiopatologia , Doença por Corpos de Lewy/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Tálamo/metabolismo , Tálamo/fisiopatologia , alfa-Sinucleína/metabolismoRESUMO
The situation of the caudal intralaminar thalamic nuclei within basal ganglia circuits has gained increased attention over the past few years. Although initially considered as a "non-specific" thalamic nuclei, tract-tracing studies carried out over the past two decades have demonstrated that the centromedian-parafascicular thalamic complex (CM-Pf) is connected to virtually all basal ganglia components and related nuclei. Although the anatomical basis sustaining the thalamic modulation of basal ganglia circuits has long been characterized, the functional significance of these transverse circuits still remain to be properly accommodated within the basal ganglia model, both under normal conditions as well as in situations of dopaminergic depletion. However, the recent demonstration of primary (e.g., non-dopamine related) neurodegenerative phenomena restricted to the CM-Pf in Parkinson's disease (PD) has renewed interest in the role played by the caudal intralaminar nuclei in the pathophysiology of PD. Concomitantly, evidence has become available of increased metabolic activity in the caudal intralaminar nuclei in rodent models of PD. Finally, CM-Pf neurosurgery in patients suffering from PD has produced contrasting outcomes, indicating that a consensus is still to be reached regarding the potential usefulness of targeting the caudal intralaminar nuclei to treat movement disorders of basal ganglia origin.
Assuntos
Núcleos Intralaminares do Tálamo/fisiopatologia , Transtornos dos Movimentos/fisiopatologia , Vias Neurais/fisiopatologia , Doença de Parkinson/fisiopatologia , Animais , Gânglios da Base/patologia , Gânglios da Base/fisiopatologia , Terapia por Estimulação Elétrica/métodos , Humanos , Núcleos Intralaminares do Tálamo/metabolismo , Núcleos Intralaminares do Tálamo/patologia , Transtornos dos Movimentos/terapia , Doença de Parkinson/terapia , Resultado do TratamentoRESUMO
The acetylcholine (ACh) innervation of thalamus arises mainly from the brainstem pedunculopontine and laterodorsal tegmental nuclei. By using immunocytochemistry with a monoclonal antibody against whole rat choline acetyltransferase (ChAT), we quantified the distribution and characterized the ultrastructural features of these nerve terminals (axon varicosities) in the dorsolateral geniculate (DLG), parafascicular (PF), and reticular thalamic (Rt) nuclei of adult rat. The regional density of ACh innervation was the highest in PF (2.1 x 10(6) varicosities/mm(3)), followed by Rt (1.7 x 10(6)) and DLG (1.3 x 10(6)). In single thin sections, ChAT-immunostained varicosity profiles appeared comparable in shape and content in the three nuclei, but significantly larger in PF than in DLG and Rt. The number of these profiles displaying a synaptic junction was also much higher in PF than in DLG and Rt, indicating that all ChAT-immunostained varicosities in PF were synaptic, but only 39% in DLG and 33% in Rt. The hypothesis that glutamate corelease might account for the maintenance of the entirely synaptic ACh innervation in PF was refuted by the lack of colocalization of ChAT and vesicular glutamate transporter 2 (VGLUT2) in PF axon varicosities after dual immunolabeling. These data suggest that diffuse as well as synaptic transmission convey modulatory effects of the ACh input from brainstem to DLG and Rt during waking. In contrast, the entirely synaptic ACh input to PF should allow for a direct relaying of the information from brainstem, affecting basal ganglia function as well as perceptual awareness, including attention and pain perception.
Assuntos
Acetilcolina/metabolismo , Fibras Colinérgicas/metabolismo , Núcleo Tegmental Pedunculopontino/metabolismo , Terminações Pré-Sinápticas/metabolismo , Tálamo/metabolismo , Animais , Nível de Alerta/fisiologia , Colina O-Acetiltransferase/metabolismo , Fibras Colinérgicas/ultraestrutura , Corpos Geniculados/metabolismo , Corpos Geniculados/ultraestrutura , Ácido Glutâmico/metabolismo , Núcleos Intralaminares do Tálamo/metabolismo , Núcleos Intralaminares do Tálamo/ultraestrutura , Masculino , Microscopia Imunoeletrônica , Vias Neurais/metabolismo , Vias Neurais/ultraestrutura , Núcleo Tegmental Pedunculopontino/ultraestrutura , Terminações Pré-Sinápticas/ultraestrutura , Ratos , Ratos Sprague-Dawley , Transmissão Sináptica/fisiologia , Tálamo/ultraestrutura , Proteína Vesicular 2 de Transporte de Glutamato/metabolismo , Vigília/fisiologiaRESUMO
The ventral part of the oral pontine reticular nucleus (vRPO) is a demonstrated site of brainstem REM-sleep generation and maintenance. The vRPO has reciprocal connections with structures that control other states of the sleep-wakefulness cycle, many situated in the basal forebrain and the diencephalon. Some of these connections utilize the inhibitory neurotransmitter GABA. The aim of the present work is to map the local origin of the basal forebrain and diencephalon projections to the vRPO whether GABAergic or non-GABAergic. A double-labelling technique combining vRPO injections of the neuronal tracer, cholera-toxin (CTB), with GAD-immunohistochemistry, was used for this purpose in adult cats. All of the numerous CTB-positive neurons in the reticular thalamic and dorsocaudal hypothalamic nuclei were double-labelled (CTB/GAD-positive) neurons. Approximately 15%, 14% and 16% of the CTB-positive neurons in the zona incerta and the dorsal and lateral hypothalamic areas are, respectively, CTB/GAD-positive neurons. However, only some double-labelled neurons were found in other hypothalamic nuclei with abundant CTB-positive neurons, such as the paraventricular nucleus, perifornical area and H1 Forel field. In addition, CTB-positive neurons were abundant in the central amygdaline nucleus, terminal stria bed nuclei, median preoptic nucleus, medial and lateral preoptic areas, dorsomedial and ventromedial hypothalamic nuclei, posterior hypothalamic area and periventricular thalamic nucleus. The GABAergic and non-GABAergic connections described here may be the morphological pillar through which these prosencephalic structures modulate, either by inhibiting or by exciting, the vRPO REM-sleep inducing neurons during the different sleep-wakefulness cycle states.
Assuntos
Diencéfalo/anatomia & histologia , Ponte/anatomia & histologia , Formação Reticular/anatomia & histologia , Sono REM/fisiologia , Telencéfalo/anatomia & histologia , Ácido gama-Aminobutírico/metabolismo , Vias Aferentes/anatomia & histologia , Vias Aferentes/metabolismo , Animais , Mapeamento Encefálico , Gatos , Toxina da Cólera , Diencéfalo/metabolismo , Glutamato Descarboxilase/metabolismo , Hipotálamo/anatomia & histologia , Hipotálamo/metabolismo , Imuno-Histoquímica , Núcleos Intralaminares do Tálamo/anatomia & histologia , Núcleos Intralaminares do Tálamo/metabolismo , Masculino , Inibição Neural/fisiologia , Neurônios/metabolismo , Ponte/metabolismo , Formação Reticular/metabolismo , Subtálamo/anatomia & histologia , Subtálamo/metabolismo , Telencéfalo/metabolismoRESUMO
The present study is focused on the analysis of the vesicular glutamate transporters 1 and 2 (VGLUT1 and VGLUT2) used by thalamic neurons giving rise to the thalamostriatal system. Instead of studying the distribution of VGLUT proteins at the level of thalamostriatal terminals, this report is focused on identifying the expression of the VGLUT mRNAs within the parent cell bodies of thalamic neurons innervating the striatum. For this purpose, we have combined dual in situ hybridization to detect both VGLUT1 and VGLUT2 mRNAs together with retrograde tracing with cholera toxin. Our results show that VGLUT2 is the only vesicular glutamate transporter expressed in thalamostriatal-projecting neurons located in the midline and intralaminar nuclei, whereas all neurons from the ventral thalamic nuclei innervating the striatum express both VGLUTs, at least at the mRNA level. Indeed, the mRNAs encoding for VGLUT1 and VGLUT2 displayed a sharp complementary subcellular distribution within neurons from the ventral thalamic nuclei giving rise to thalamostriatal projections. The differential distribution of VGLUT mRNAs lead us to conclude that the thalamostriatal pathway is a dual system, composed by a preponderant projection arising from the midline and intralaminar nuclei using VGLUT2 as the glutamate transporter, together with another important source of striatal afferents arising from neurons in the ventral thalamic relay nuclei containing both kinds of vesicular glutamate transporters.
Assuntos
Corpo Estriado/metabolismo , Ácido Glutâmico/metabolismo , Tálamo/metabolismo , Proteína Vesicular 1 de Transporte de Glutamato/genética , Proteína Vesicular 2 de Transporte de Glutamato/genética , Animais , Mapeamento Encefálico , Toxina da Cólera/metabolismo , Corpo Estriado/citologia , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Núcleos Intralaminares do Tálamo/citologia , Núcleos Intralaminares do Tálamo/metabolismo , Masculino , Núcleos da Linha Média do Tálamo/citologia , Núcleos da Linha Média do Tálamo/metabolismo , Vias Neurais/citologia , Vias Neurais/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Coloração e Rotulagem , Transmissão Sináptica/fisiologia , Tálamo/citologiaRESUMO
Vesicular glutamate transporters (VGLUTs) are responsible for glutamate trafficking and for the subsequent regulated release of this excitatory neurotransmitter at the synapse. Three isoforms of the VGLUT have been identified, now known as VGLUT1, VGLUT2, and VGLUT3. Both VGLUT1 and VGLUT2 have been considered definitive markers of glutamatergic neurons, whereas VGLUT3 is expressed in nonglutamatergic neurons such as cholinergic striatal interneurons. It is widely believed that VGLUT1 and VGLUT2 are expressed in a complementary manner at the cortical and thalamic levels, suggesting that these glutamatergic neurons fulfill different physiological functions. In the present work, we analyzed the pattern of VGLUT1 and VGLUT2 mRNA expression at the thalamic level by using single and dual in situ hybridization. In accordance with current beliefs, we found significant expression of VGLUT2 mRNA in all the thalamic nuclei, while moderate expression of VGLUT1 mRNA was consistently found in both the principal relay and the association thalamic nuclei. Interestingly, individual neurons within these nuclei coexpressed both VGLUT1 and VGLUT2 mRNAs, suggesting that these individual thalamic neurons may have different ways of trafficking glutamate. These results call for a reappraisal of the previously held concept regarding the mutually exclusive distribution of VGLUT transporters in the central nervous system.
Assuntos
RNA Mensageiro/metabolismo , Tálamo/metabolismo , Proteína Vesicular 1 de Transporte de Glutamato/genética , Proteína Vesicular 2 de Transporte de Glutamato/genética , Animais , Biomarcadores/análise , Biomarcadores/metabolismo , Ácido Glutâmico/metabolismo , Habenula/anatomia & histologia , Habenula/metabolismo , Hibridização In Situ , Núcleos Intralaminares do Tálamo/anatomia & histologia , Núcleos Intralaminares do Tálamo/metabolismo , Masculino , Vias Neurais/anatomia & histologia , Vias Neurais/metabolismo , Ratos , Ratos Wistar , Transmissão Sináptica/fisiologia , Tálamo/anatomia & histologiaRESUMO
Immunohistochemical methods were used to label singly and/or in combination glutamic acid decarboxylase (GAD, the sole synthesizing enzyme for the inhibitory neurotransmitter gamma-aminobutyric acid) and phosphate-activated glutaminase (GLN, a synthesizing enzyme for glutamate) in neurons of lateral reticular nucleus (LRN) of thalamus of adult cats. (1) GAD- and GLN-immunoreactivity (IR) exhibited matching regional patterns of organization within LRN. (2) GAD- and GLN-IR co-localized within most if not all LRN neuronal cell bodies as shown by light microscopy. (3) GAD- and GLN-IR had distinct subcellular localizations in LRN neurons as shown by correlative light/electron microscopy. LRN neurons are important conceptual models where strongly inhibitory cells receive predominant excitatory glutamatergic afferents (from neocortex). Consistent with known actions of intermediary astrocytes, LRN neurons demonstrate GLN enrichment synergistically coupled with glutamatergic innervation to supplement the glutamate pool for GABA synthesis (via GAD) and for metabolic utilization (via the GABA shunt/tricarboxylic acid cycle) but not, apparently, for excitatory neurotransmission.
Assuntos
Glutamato Descarboxilase/biossíntese , Glutaminase/biossíntese , Núcleos Intralaminares do Tálamo/metabolismo , Neurônios/metabolismo , Animais , Gatos , Feminino , Imuno-Histoquímica , Masculino , Microscopia Eletrônica , FotomicrografiaRESUMO
Many studies have implicated GABA(B) receptors in pain transmission mechanisms, especially in the spinal cord. In the thalamus, mRNA expression of the GABA(B(1b)) isoform was shown to be regulated in relay nuclei in response to chronic noxious input arising from experimental monoarthritis. GABA(B(1a)) and GABA(B2) mRNA expression was here determined by in situ hybridisation in the brain of control, 2, 4, 7 and 14 days monoarthritic rats, to evaluate whether this expression was regulated by chronic noxious input in thalamic nuclei. mRNA labelling was analysed quantitatively in the ventrobasal complex, posterior, central medial/central lateral and reticular thalamic nuclei; the thalamic visual relay and dentate gyrus were examined for control. No mRNA expression was detected for GABA(B(1a)) in control and monoarthritic animals. Similarly, GABA(B2) mRNA was not found in the reticular nucleus. However, GABA(B2) mRNA expression was observed in the ventrobasal complex, posterior and central medial/central lateral nuclei of control animals. A significant decrease of 42% at 2 days and 27% at 4 days of monoarthritis was observed in the ventrobasal complex contralaterally, when compared with controls, returning to basal levels at 7 days of monoarthritis. In the ipsilateral posterior nucleus, there was a significant decrease of 38% at 2 days of monoarthritis. No significant changes were observed in central medial/central lateral nuclei. The data suggest that GABA(B2) mRNA expression in the ventrobasal complex and posterior nucleus is regulated by noxious input and that GABA(B) receptors might play a role in the plasticity of these relay nuclei during chronic inflammatory pain.
Assuntos
Artralgia/fisiopatologia , Artrite/fisiopatologia , RNA Mensageiro/metabolismo , Receptores de GABA-A/genética , Tálamo/fisiopatologia , Vias Aferentes/metabolismo , Vias Aferentes/fisiopatologia , Animais , Artralgia/genética , Artralgia/metabolismo , Artrite/genética , Artrite/metabolismo , Doença Crônica , Modelos Animais de Doenças , Regulação para Baixo/fisiologia , Lateralidade Funcional/fisiologia , Núcleos Intralaminares do Tálamo/metabolismo , Núcleos Intralaminares do Tálamo/fisiopatologia , Masculino , Inibição Neural/fisiologia , Plasticidade Neuronal/fisiologia , Nociceptores/metabolismo , Núcleos Posteriores do Tálamo/metabolismo , Núcleos Posteriores do Tálamo/fisiopatologia , Ratos , Ratos Wistar , Tálamo/metabolismo , Fatores de Tempo , Núcleos Ventrais do Tálamo/metabolismo , Núcleos Ventrais do Tálamo/fisiopatologia , Ácido gama-Aminobutírico/metabolismoRESUMO
The ventrolateral part of the parafascicular thalamic nucleus (PF), which is considered to take part in the control mechanism of orofacial motor functions, receives projection fibers not only from the dorsolateral part of the substantia nigra pars reticulata (SNr) but also from the ventral part of the reticular thalamic nucleus (RT) [Tsumori et al., Brain Res. 858 (2000) 429]. In order to better understand the influence of these fibers upon the PF projection neurons, the morphology, synaptology and chemical nature of them were examined in the present study. After ipsilateral injections of Phaseolus vulgaris-leucoagglutinin (PHA-L) into the dorsolateral part of the SNr and biotinylated dextran amine (BDA) into the ventral part of the RT, overlapping distributions of PHA-L-labeled SNr fibers and BDA-labeled RT fibers were seen in the ventrolateral part of the PF. At the electron microscopic level, the SNr terminals made synapses predominantly with the medium to small dendrites and far less frequently with the somata and large dendrites, whereas approximately half of the RT terminals made synapses with the somata and large dendrites and the rest did with the medium to small dendrites of PF neurons. Some of single dendritic as well as single somatic profiles received convergent synaptic inputs from both sets of terminals. These terminals were packed with pleomorphic synaptic vesicles and formed symmetrical synapses. After combined injections of PHA-L into the dorsolateral part of the SNr, BDA into the ventral part of the RT and wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into the ventrolateral part of the striatum or into the rostroventral part of the lateral agranular cortex, WGA-HRP-labeled neurons were embedded in the plexus of PHA-L- and BDA-labeled axon terminals within the ventrolateral part of the PF, where the PHA-L- and/or BDA-labeled terminals were in synaptic contact with single somatic and dendritic profiles of the WGA-HRP-labeled neurons. Furthermore, the SNr and RT axon terminals were revealed to be immunoreactive for gamma-aminobutyric acid (GABA), by using the anterograde BDA tracing technique combined with immunohistochemistry for GABA. The present data suggest that GABAergic SNr and RT fibers may exert different inhibitory influences on the PF neurons for regulating the thalamic outflow from the PF to the cerebral cortex and/or striatum in the control of orofacial movements.
Assuntos
Núcleos Intralaminares do Tálamo/ultraestrutura , Inibição Neural/fisiologia , Vias Neurais/ultraestrutura , Terminações Pré-Sinápticas/ultraestrutura , Substância Negra/ultraestrutura , Ácido gama-Aminobutírico/metabolismo , Animais , Corpo Estriado/metabolismo , Corpo Estriado/ultraestrutura , Dendritos/metabolismo , Dendritos/ultraestrutura , Imuno-Histoquímica , Núcleos Intralaminares do Tálamo/metabolismo , Masculino , Microscopia Eletrônica , Córtex Motor/metabolismo , Córtex Motor/ultraestrutura , Vias Neurais/metabolismo , Terminações Pré-Sinápticas/metabolismo , Ratos , Ratos Wistar , Substância Negra/metabolismo , Transmissão Sináptica/fisiologiaRESUMO
Cajal's many contributions to understanding the thalamus have been hidden by his body of work on the cerebral cortex. He delineated many thalamic nuclei in rodents, defined afferent fibers, thalamocortical relay neurons and interneurons, was first to demonstrate thalamocortical fibers and their terminations in the cortex, and recognized the feed-back provided by corticothalamic fibers. This presentation outlines modern methods for identifying classes of thalamic neurons, their chemical characteristics, synaptology and differential connections, and describes the intrinsic circuitry of the thalamus, showing how interactions between GABAergic cells of the reticular nucleus and glutamatergic relay cells underlie rhythmic activities of neurons in the thalamo-cortico-thalamic network, activities associated with changes in the conscious state, and which are generated and maintained by the corticothalamic projection. Corticothalamic fibers interact with reticular nucleus cells and relay cells through NMDA, AMPA and metabotropic receptors while interactions between reticular nucleus cells and relay cells are mediated by GABAA and GABAB receptors. Differing strengths of synaptic input to the two cell types, from which oscillatory behavior commences, depend upon differential expression at individual synapses of specific AMPA receptor subunits which modulate excitatory postsynaptic conductances. Two classes of relay cells can be distinguished by differential staining for calbindin and parvalbumin. The first forms a matrix in the thalamus, unconstrained by nuclear borders; the second is concentrated in certain nuclei in which it forms the topographically organized core. In projecting diffusely to the cortex, calbindin cells provide a substrate for binding together activities of multiple cortical areas that receive focused input from single thalamic nuclei. This, and the presence of specific and diffuse corticothalamic projections may serve to promote coherent activity of large populations of cortical and thalamic neurons in perception, attention and conscious awareness.
Assuntos
Vias Neurais/ultraestrutura , Neurônios/ultraestrutura , Tálamo/ultraestrutura , Animais , Relógios Biológicos/fisiologia , Córtex Cerebral/metabolismo , Córtex Cerebral/ultraestrutura , Humanos , Interneurônios/metabolismo , Interneurônios/ultraestrutura , Núcleos Intralaminares do Tálamo/metabolismo , Núcleos Intralaminares do Tálamo/ultraestrutura , Inibição Neural/fisiologia , Vias Neurais/metabolismo , Neurônios/metabolismo , Terminações Pré-Sinápticas/metabolismo , Terminações Pré-Sinápticas/ultraestrutura , Tálamo/metabolismoRESUMO
To study the antiepileptic mechanism of vagus nerve stimulation (VNS), we used the methods of in situ hybridyzation and image analysis to detect the expression of NMDAR1 mRNA and GABAA receptor alpha 1 subunit mRNA (GABAAR alpha 1 mRNA) in the thalamic reticular nuclus. The results show that the NMDAR1 mRNA expression of rats administered pentylenetetrazole(PTZ) is higher than that of control group. By treating with VNS, it decreased. On the contrary, the expression of GABAAR alpha 1 mRNA in the thalamic reticular nuclus of PTZ group rats is lower than that of control group. For rats treated with VNS, it increased. Therefore, it is concluded that VNS may reduce the excitability of cerebral cortices by depressing the activities of glutamic acid receptors (GluR) and by promoting the activities of gamma-aminobutyric acid receptors(GABAR) in thalamic reticular nuclus. So the formation and development of seizures are inhibited.
Assuntos
Terapia por Estimulação Elétrica/métodos , Epilepsia/terapia , Núcleos Intralaminares do Tálamo/metabolismo , Receptores de GABA-A/biossíntese , Receptores de N-Metil-D-Aspartato/biossíntese , Nervo Vago , Animais , Epilepsia/induzido quimicamente , Masculino , Pentilenotetrazol/toxicidade , RNA Mensageiro/biossíntese , Ratos , Ratos Wistar , Receptores de GABA-A/genética , Receptores de N-Metil-D-Aspartato/genética , Nervo Vago/fisiopatologiaRESUMO
Corticotropin-releasing hormone (CRH) coordinates multiple aspects of the stress response. Recently, CRH mRNA has been identified in two regions of the thalamus: the posterior nuclear group (Po), and a region located at the interface of the central medial and ventral posteromedial nucleus (parvicellular part) (CM-VPMpc). Previous studies demonstrated that in both regions CRH mRNA increases following 1 h of restraint stress, suggesting involvement of thalamic CRH in processing somatosensory and visceral information related to stress. The current study was proposed to further understand the effects of repeated and acute restraint stress on levels of thalamic CRH mRNA. Adult male rats were assigned to one of four groups in a 2 (repeated stress, no repeated) x2 (acute, no acute) design. Brain sections were processed for CRH mRNA in situ hybridization. ANOVA revealed no main effects of acute or repeated stress in either thalamic region. However, significant interactions between acute and repeated stress for levels of CRH mRNA were found for both regions of the thalamus. Compared to the no stress condition, acute restraint significantly increased CRH mRNA in the Po (39%) and the CM-VPMpc (32%). Repeated restraint did not alter baseline CRH mRNA levels, but blocked the acute restraint-induced effects. Thus, while acute stress increases levels of thalamic CRH mRNA, repeated exposure to the same stressor is without effect and prevents the acute response. These findings add to data establishing a role for thalamic CRH in the stress response and suggest a mechanism that may underlie habituation to repeated stress exposure.
Assuntos
Hormônio Liberador da Corticotropina/genética , Neurônios/metabolismo , RNA Mensageiro/metabolismo , Estresse Fisiológico/metabolismo , Tálamo/metabolismo , Regulação para Cima/genética , Doença Aguda , Animais , Regulação da Expressão Gênica/fisiologia , Núcleos Intralaminares do Tálamo/citologia , Núcleos Intralaminares do Tálamo/metabolismo , Masculino , Neurônios/citologia , Dor/metabolismo , Dor/fisiopatologia , Núcleos Posteriores do Tálamo/citologia , Núcleos Posteriores do Tálamo/metabolismo , Ratos , Ratos Sprague-Dawley , Restrição Física , Estresse Fisiológico/genética , Estresse Fisiológico/fisiopatologia , Tálamo/citologia , Tato/fisiologia , Núcleos Ventrais do Tálamo/citologia , Núcleos Ventrais do Tálamo/metabolismoRESUMO
All senses, except olfaction, are routed through the thalamus to cerebral cortex. Thus, the thalamus is often referred to as the sensory gateway to cortex. Located between thalamus and cortex is a thin lamina of neurons called the thalamic reticular nucleus, which may function as an attentional gate. The phenomenon of blocking in classical conditioning provides an opportunity to test whether an attended stimulus activates the thalamic reticular nucleus more than an unattended stimulus: when a second stimulus is presented together with a previously conditioned stimulus, conditioned responding to the second stimulus is inhibited. Different groups of rats were given conditioning sessions with a single stimulus, a light or a tone, and then given conditioning sessions with compound (light and tone) stimuli. Blocking was confirmed using probe trials of single stimulus presentations. After a final test session of compound stimulus presentations, the brains were processed for the presence of Fos protein. Here we show that Fos-positive neurons were more numerous in the sector of the thalamic reticular nucleus associated with the attended conditioned stimulus than in the sector associated with the unattended stimulus. Thus, we provide evidence for an involvement of the thalamic reticular nucleus in selective attention.