RESUMO
Persistent activity underlying short-term memory encodes sensory information or instructs specific future movement and, consequently, has a crucial role in cognition. Despite extensive study, how the same set of neurons respond differentially to form selective persistent activity remains unknown. Here, we report that the cortico-basal ganglia-thalamo-cortical (CBTC) circuit supports the formation of selective persistent activity in mice. Optogenetic activation or inactivation of the basal ganglia output nucleus substantia nigra pars reticulata (SNr)-to-thalamus pathway biased future licking choice, without affecting licking execution. This perturbation differentially affected persistent activity in the frontal cortex and selectively modulated neural trajectory that encodes one choice but not the other. Recording showed that SNr neurons had selective persistent activity distributed across SNr, but with a hotspot in the mediolateral region. Optogenetic inactivation of the frontal cortex also differentially affected persistent activity in the SNr. Together, these results reveal a CBTC channel functioning to produce selective persistent activity underlying short-term memory.
Assuntos
Memória de Curto Prazo , Parte Reticular da Substância Negra , Animais , Gânglios da Base/fisiologia , Camundongos , Vias Neurais/fisiologia , Parte Reticular da Substância Negra/fisiologia , Substância Negra/fisiologia , Tálamo/fisiologiaRESUMO
Models of basal ganglia (BG) function predict that tonic inhibitory output to motor thalamus (MT) suppresses unwanted movements, and that a decrease in such activity leads to action selection. Further, for unilateral activity changes in the BG, a lateralized effect on contralateral movements can be expected due to ipsilateral thalamocortical connectivity. However, a direct test of these outcomes of thalamic inhibition has not been performed. To conduct such a direct test, we utilized rapid optogenetic activation and inactivation of the GABAergic output of the substantia nigra pars reticulata (SNr) to MT in male and female mice that were trained in a sensory cued left/right licking task. Directional licking tasks have previously been shown to depend on a thalamocortical feedback loop between ventromedial MT and antero-lateral premotor cortex. In confirmation of model predictions, we found that unilateral optogenetic inhibition of GABAergic output from the SNr, during ipsilaterally cued trials, biased decision making towards a contralateral lick without affecting motor performance. In contrast, optogenetic excitation of SNr terminals in MT resulted in an opposite bias towards the ipsilateral direction confirming a bidirectional effect of tonic nigral output on directional decision making. However, direct optogenetic excitation of neurons in the SNr resulted in bilateral movement suppression, which is in agreement with previous results that show such suppression for nigral terminals in the superior colliculus (SC), which receives a bilateral projection from SNr.
Assuntos
Gânglios da Base/fisiologia , Tomada de Decisões/fisiologia , Movimento/fisiologia , Inibição Neural/fisiologia , Substância Negra/fisiologia , Animais , Antecipação Psicológica/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Dependovirus/genética , Feminino , Lateralidade Funcional/fisiologia , Masculino , Camundongos , Córtex Motor/fisiologia , Vias Neurais/fisiologia , Optogenética , Substância Negra/efeitos dos fármacos , Tálamo/fisiologia , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/genéticaRESUMO
Glutamatergic projections of the thalamic rostral intralaminar nuclei of the thalamus (rILN) innervate the dorsal striatum (DS) and are implicated in dopamine (DA)-dependent incubation of drug seeking. However, the mechanism by which rILN signaling modulates reward seeking and striatal DA release is unknown. We find that activation of rILN inputs to the DS drives cholinergic interneuron burst-firing behavior and DA D2 receptor-dependent post-burst pauses in cholinergic interneuron firing. In vivo, optogenetic activation of this pathway drives reinforcement in a DA D1 receptor-dependent manner, and chemogenetic suppression of the rILN reduces dopaminergic nigrostriatal terminal activity as measured by fiber photometry. Altogether, these data provide evidence that the rILN activates striatal cholinergic interneurons to enhance the pursuit of reward through local striatal DA release and introduce an additional level of complexity in our understanding of striatal DA signaling.
Assuntos
Corpo Estriado/fisiologia , Dopamina/metabolismo , Recompensa , Tálamo/fisiologia , Animais , Corpo Estriado/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Optogenética , Substância Negra/metabolismo , Substância Negra/fisiologia , Tálamo/metabolismoRESUMO
Although attention deficit hyperactivity disorder is associated with deficits in docosahexaenoic acid (DHA), an omega-3 fatty acid implicated in dopamine and glutamate synaptic plasticity, its role in neuroplastic brain changes that occur following repeated amphetamine (AMPH) treatment are not known. This study used pharmacological magnetic resonance imaging to investigate the impact of repeated AMPH exposure and alterations in brain DHA levels on AMPH-induced brain activation patterns. Male rats were fed a diet with no n-3 fatty acids (Deficient, DEF, n = 20), a diet fortified with preformed DHA (fish oil, FO, n = 20), or a control diet fortified with alpha-linolenic acid (n = 20) from P21 to P90. During adolescence (P40-60), one-half of each diet group received daily AMPH injections escalated weekly (0.5, 1.0, 2.5, 5.0â mg/kg/d) or drug vehicle. Following a 30-d abstinence period blood oxygen level dependent (BOLD) responses were determined in a 7â T Bruker Biospec system following an AMPH challenge (7.5â mg/kg, i.v). Postmortem erythrocyte and forebrain DHA composition were determined by gas chromatography. Compared with control rats, forebrain and erythrocyte DHA levels were significantly lower in DEF rats and significantly higher in FO rats. Across AMPH doses DEF rats exhibited greater locomotor activity compared to control and FO rats. In AMPH-naïve rats, the AMPH challenge increased BOLD activity in the substantia nigra and basal forebrain and no diet group differences were observed. In AMPH-pretreated control and FO rats, the AMPH challenge similarly increased BOLD activation in the bilateral caudate putamen, thalamus, and motor and cingulate cortices. In contrast, BOLD activation in AMPH-pretreated DEF rats was similar to AMPH-naïve DEF animals, and AMPH-pretreated DEF rats exhibited attenuated frontostriatal BOLD activation compared with AMPH-pretreated control and FO rats. These findings demonstrate that chronic escalating AMPH treatment induces enduring frontostriatal recruitment and that peri-adolescent deficits in brain DHA accrual impair this response.
Assuntos
Anfetamina/administração & dosagem , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Ácidos Docosa-Hexaenoicos/administração & dosagem , Animais , Prosencéfalo Basal/efeitos dos fármacos , Prosencéfalo Basal/fisiologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/fisiologia , Ácidos Docosa-Hexaenoicos/metabolismo , Eritrócitos/metabolismo , Giro do Cíngulo/efeitos dos fármacos , Giro do Cíngulo/fisiologia , Locomoção/efeitos dos fármacos , Imageamento por Ressonância Magnética , Masculino , Córtex Motor/efeitos dos fármacos , Córtex Motor/fisiologia , Prosencéfalo/metabolismo , Ratos Long-Evans , Substância Negra/efeitos dos fármacos , Substância Negra/fisiologia , Tálamo/efeitos dos fármacos , Tálamo/fisiologiaRESUMO
To investigate the effects of Lycium barbarum polysaccharide (LBP) on pathological symptoms and behavioral deficits in a Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. The therapeutic effects of LBP were monitored with an Open field test, a Rotarod test and a Morris water maze test. We also investigated the mechanisms with qRT-PCR and Western blotting analyses. After a relatively short-term LBP treatment, the total distance and walking time of PD mice significantly increased. The staying duration on the rod of PD mice increased in the Rotarod test. LBP can up-regulate levels of SOD2, CAT and GPX1 and inhibit the abnormal aggregation of α-synuclein induced by MPTP. LBP treatment can also up-regulate the phosphorylation of AKT and mTOR, and may play its protective role by activating the PTEN/AKT/mTOR signaling axis. These results suggest that LBP can effectively alleviate the degeneration in the nigrostriatal system induced by MPTP treatment. It may be a potential candidate for the treatment of Parkinson's disease.
Assuntos
Dopamina/fisiologia , Medicamentos de Ervas Chinesas/farmacologia , PTEN Fosfo-Hidrolase/metabolismo , Transtornos Parkinsonianos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/fisiologia , Medicamentos de Ervas Chinesas/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transtornos Parkinsonianos/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Substância Negra/efeitos dos fármacos , Substância Negra/fisiologiaRESUMO
The acoustic startle reflex (ASR) is a short and intense defensive reaction in response to a loud and unexpected acoustic stimulus. In the rat, a primary startle pathway encompasses three serially connected central structures: the cochlear root neurons, the giant neurons of the nucleus reticularis pontis caudalis (PnC), and the spinal motoneurons. As a sensorimotor interface, the PnC has a central role in the ASR circuitry, especially the integration of different sensory stimuli and brain states into initiation of motor responses. Since the basal ganglia circuits control movement and action selection, we hypothesize that their output via the substantia nigra (SN) may interplay with the ASR primary circuit by providing inputs to PnC. Moreover, the pedunculopontine tegmental nucleus (PPTg) has been proposed as a functional and neural extension of the SN, so it is another goal of this study to describe possible anatomical connections from the PPTg to PnC. Here, we made 6-OHDA neurotoxic lesions of the SN pars compacta (SNc) and submitted the rats to a custom-built ASR measurement session to assess amplitude and latency of motor responses. We found that following lesion of the SNc, ASR amplitude decreased and latency increased compared to those values from the sham-surgery and control groups. The number of dopamine neurons remaining in the SNc after lesion was also estimated using a stereological approach, and it correlated with our behavioral results. Moreover, we employed neural tract-tracing techniques to highlight direct projections from the SN to PnC, and indirect projections through the PPTg. Finally, we also measured levels of excitatory amino acid neurotransmitters in the PnC following lesion of the SN, and found that they change following an ipsi/contralateral pattern. Taken together, our results identify nigrofugal efferents onto the primary ASR circuit that may modulate motor responses.
Assuntos
Vias Auditivas/fisiologia , Movimento/fisiologia , Reflexo de Sobressalto/fisiologia , Formação Reticular/fisiologia , Substância Negra/fisiologia , Estimulação Acústica , Animais , Vias Auditivas/efeitos dos fármacos , Biotina/análogos & derivados , Biotina/metabolismo , Conectoma , Dextranos/metabolismo , Lateralidade Funcional/efeitos dos fármacos , Masculino , NADPH Desidrogenase/metabolismo , Neurotoxinas/toxicidade , Neurotransmissores/metabolismo , Oxidopamina/toxicidade , Ratos , Ratos Wistar , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Reflexo de Sobressalto/efeitos dos fármacos , Formação Reticular/efeitos dos fármacos , Medula Espinal/citologia , Medula Espinal/efeitos dos fármacos , Estilbamidinas/metabolismo , Substância Negra/lesões , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
In this paper, we used a classic basal ganglia-corticothalamic model(BGCT) to study the onset and control mechanism of absence epilepsy in specific relay nuclei (SRN) of thalamus. It was found that the seizure state may appear in SRN by turning the coupling strength -vsr and signal transmission delay τ on the route "Thalamic reticular nuclei (TRN) of thalamus ⶠSRN". With increasing of -vsr, the seizure state appeared two times, and its onset mechanism has not been discussed in previous studies. The seizure activity can be well controlled by adjusting the activation level of the substantia nigra pars reticulata (SNr) in basal ganglia, which is a main output tissue to the corticothalamic system through two direct inhibitory pathways "SNr ⶠSRN" and "SNr ⶠTRN" in our model. We found that the interesting bidirectional regulation phenomenon appeared as considering the single pathway "SNr ⶠSRN" and "SNr ⶠTRN", or when they coexisted in one network, the mechanism of which is also different from some previous theoretical studies. At last, we pointed out that the mechanism obtained above can also explain the onset and control of the poly-spikes slow wave appeared in SRN by turning τ to large enough. Therefore, the results in the paper will further deepen our understanding of the generation and control mechanism of epilepsy disease.
Assuntos
Epilepsia Tipo Ausência/fisiopatologia , Modelos Neurológicos , Convulsões/fisiopatologia , Tálamo/fisiologia , Animais , Eletroencefalografia , Humanos , Vias Neurais , Parte Reticular da Substância Negra/fisiologia , Substância Negra/fisiologiaRESUMO
Appetite and body weight regulation are controlled by the central nervous system (CNS) in a rather complicated manner. The human brain plays a central role in integrating internal and external inputs to modulate energy homeostasis. Although homeostatic control by the hypothalamus is currently considered to be primarily responsible for controlling appetite, most of the available evidence derives from experiments in rodents, and the role of this system in regulating appetite in states of hunger/starvation and in the pathogenesis of overeating/obesity remains to be fully elucidated in humans. Further, cognitive and affective processes have been implicated in the dysregulation of eating behavior in humans, but their exact relative contributions as well as the respective underlying mechanisms remain unclear. We briefly review each of these systems here and present the current state of research in an attempt to update clinicians and clinical researchers alike on the status and future directions of obesity research.
Assuntos
Regulação do Apetite , Sistema Nervoso Central/fisiologia , Modelos Neurológicos , Neurônios/fisiologia , Mapeamento Encefálico , Sistema Nervoso Central/fisiopatologia , Cognição , Neurônios Dopaminérgicos/fisiologia , Emoções , Ingestão de Energia , Metabolismo Energético , Neuroimagem Funcional , Humanos , Hipotálamo/fisiologia , Hipotálamo/fisiopatologia , Memória , Núcleo Accumbens/fisiologia , Núcleo Accumbens/fisiopatologia , Obesidade/metabolismo , Obesidade/fisiopatologia , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/fisiopatologia , Recompensa , Substância Negra/fisiologia , Substância Negra/fisiopatologia , Área Tegmentar Ventral/fisiologia , Área Tegmentar Ventral/fisiopatologiaRESUMO
Recent findings from our lab indicate that metabotropic glutamate receptor (mGluR) activation elicits eating, and the goal of the current study was to specify whether the lateral hypothalamus (LH) is the actual brain site mediating this effect. To examine this issue we injected the selective mGluR group I agonist (S)-3,5-dihydroxyphenylglycine (DHPG) unilaterally into the LH and surrounding regions (n=5-8 subjects/brain site) of satiated adult male Sprague-Dawley rats and measured elicited feeding. We determined that 1.0 nmol elicited food intake only within the LH. Increasing the dose to 10 or 25 nmol produced a more sustained effect in the LH, and also elicited eating in several other brain sites. These results, demonstrating that the LH mediates the eating elicited by low doses of DHPG, suggest that the LH may contain mGluR whose activation can produce eating behavior.
Assuntos
Ingestão de Alimentos/fisiologia , Região Hipotalâmica Lateral/fisiologia , Receptor de Glutamato Metabotrópico 5/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/fisiologia , Animais , Relação Dose-Resposta a Droga , Ingestão de Alimentos/efeitos dos fármacos , Agonistas de Aminoácidos Excitatórios/farmacologia , Glicina/análogos & derivados , Glicina/farmacologia , Região Hipotalâmica Lateral/efeitos dos fármacos , Masculino , Núcleo Mediodorsal do Tálamo/efeitos dos fármacos , Núcleo Mediodorsal do Tálamo/fisiologia , Ratos Sprague-Dawley , Receptor de Glutamato Metabotrópico 5/agonistas , Receptores de Glutamato Metabotrópico/agonistas , Resorcinóis/farmacologia , Saciação/efeitos dos fármacos , Saciação/fisiologia , Substância Negra/efeitos dos fármacos , Substância Negra/fisiologia , Tálamo/efeitos dos fármacos , Tálamo/fisiologiaRESUMO
Human decision making in situations of inequity has long been regarded as a competition between the sense of fairness and self-interest, primarily based on behavioral and neuroimaging studies of inequity that disfavor the actor while favoring others. Here, we use functional magnetic resonance imaging experiments to study refusals and protests using both favoring and disfavoring inequity in three economic exchange games with undercompensating, nearly equal, and overcompensating offers. Refusals of undercompensating offers recruited a heightened activity in the right dorsolateral prefrontal cortex (dlPFC). Accepting of overcompensating offers recruited significantly higher node activity in, and network activity among, the caudate, the cingulate cortex, and the thalamus. Protesting of undercompensating fixed offers activated the network consisting of the right dlPFC and the left ventrolateral prefrontal cortex and midbrain in the substantia nigra. These findings suggest that perceived fairness and social decisions are the results of coordination between evaluated fairness norms, self-interest, and reward.
Assuntos
Encéfalo/fisiologia , Tomada de Decisões/fisiologia , Percepção/fisiologia , Recompensa , Adulto , Mapeamento Encefálico/métodos , Núcleo Caudado/fisiologia , Feminino , Giro do Cíngulo/fisiologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Rede Nervosa/fisiologia , Córtex Pré-Frontal/fisiologia , Comportamento Social , Substância Negra/fisiologia , Tálamo/fisiologia , Adulto JovemRESUMO
The basal ganglia (BG), which influence cortical activity via the thalamus, play a major role in motor activity, learning and memory, sensory processing, and many aspects of behavior. The substantia nigra (SN) consists of GABAergic neurons of the pars reticulata that inhibit thalamic neurons and provide the primary output of the BG, and dopaminergic neurons of the pars compacta that modulate thalamic excitability. Little is known about the functional properties of the SNâthalamus synapses, and anatomical characterization has been controversial. Here we use a combination of anatomical, electrophysiological, genetic, and optogenetic approaches to re-examine these synaptic connections in mice. We find that neurons in the SN inhibit neurons in the ventroposterolateral nucleus of the thalamus via GABAergic synapses, excite neurons in the thalamic nucleus reticularis, and both excite and inhibit neurons within the posterior nucleus group. Glutamatergic SN neurons express the vesicular glutamate receptor transporter vGluT2 and receive inhibitory synapses from striatal neurons, and many also express tyrosine hydroxylase, a marker of dopaminergic neurons. Thus, in addition to providing inhibitory outputs, which is consistent with the canonical circuit, the SN provides glutamatergic outputs that differentially target thalamic nuclei. This suggests that an increase in the activity of glutamatergic neurons in the SN allows the BG to directly excite neurons in specific thalamic nuclei. Elucidating an excitatory connection between the BG and the thalamus provides new insights into how the BG regulate thalamic activity, and has important implications for understanding BG function in health and disease.
Assuntos
Gânglios da Base/citologia , Inibição Neural/fisiologia , Substância Negra/fisiologia , Tálamo/fisiologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Gânglios da Base/fisiologia , Channelrhodopsins , Dependovirus/genética , Glutamato Descarboxilase/genética , Glutamato Descarboxilase/metabolismo , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Inibição Neural/efeitos dos fármacos , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiologia , Neurotransmissores/farmacologia , Estimulação Luminosa , Proteína Vesicular 2 de Transporte de Glutamato/genéticaRESUMO
Obesity resistance due to elevated orexin signaling is accompanied by high levels of spontaneous physical activity (SPA). The behavioral and neural mechanisms underlying this observation have not been fully worked out. We determined the contribution of hypothalamic orexin receptors (OXRs) to SPA stimulated by orexin A (OXA), whether OXA-stimulated SPA was secondary to arousal and whether voluntary wheel running led to compensations in 24-h SPA. We further tested whether orexin action on dopamine one receptors (DA1R) in the substantia nigra (SN) plays an important role in the generation of SPA. To test this, SPA response was determined in lean and obese rats with cannulae targeted toward the rostral lateral hypothalamus (rLH) or SN. Sleep/wake states were also measured in rats with rLH cannula and electroencephalogram/electromyogram radiotelemetry transmitters. SPA in lean rats was more sensitive to antagonism of the OX1R and in the early response to the orexin 2 agonist. OXA increased arousal equally in lean and obese rodents, which is discordant from the greater SPA response in lean rats. Obesity-resistant rats ran more and wheel running was directly related to 24-h SPA levels. The OX1R antagonist, SB-334867-A, and the DA1R antagonist, SCH3390, in SN more effectively reduced SPA stimulated by OXA in obesity-resistant rats. These data suggest OXA-stimulated SPA is not secondary to enhanced arousal, propensity for SPA parallels inclination to run and that orexin action on dopaminergic neurons in SN may participate in the mediation of SPA and running wheel activity.
Assuntos
Atividade Motora/fisiologia , Obesidade/fisiopatologia , Fatores Etários , Animais , Benzazepinas/farmacologia , Benzoxazóis/farmacologia , Peso Corporal/efeitos dos fármacos , Antagonistas de Dopamina/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Eletromiografia , Movimentos Oculares/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Hipotálamo/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/farmacologia , Masculino , Atividade Motora/efeitos dos fármacos , Naftiridinas , Neuropeptídeos/farmacologia , Antagonistas dos Receptores de Orexina , Orexinas , Ratos , Ratos Sprague-Dawley , Sono/efeitos dos fármacos , Substância Negra/efeitos dos fármacos , Substância Negra/fisiologia , Ureia/análogos & derivados , Ureia/farmacologia , Vigília/efeitos dos fármacosRESUMO
BACKGROUND: Our previous study demonstrated that essential fatty acid (EFA) dietary restriction over two generations induced midbrain dopaminergic cell loss and oxidative stress in the substantia nigra (SN) but not in the striatum of young rats. In the present study we hypothesized that omega-3 deficiency until adulthood would reduce striatum's resilience, increase nitric oxide (NO) levels and the number of BDNF-expressing neurons, both potential mechanisms involved in SN neurodegeneration. METHODS: Second generation rats were raised from gestation on control or EFA-restricted diets until young or adulthood. Lipoperoxidation, NO content, total superoxide dismutase (t-SOD) and catalase enzymatic activities were assessed in the SN and striatum. The number of tyrosine hydroxylase (TH)- and BDNF-expressing neurons was analyzed in the SN. RESULTS: Increased NO levels were observed in the striatum of both young and adult EFA-deficient animals but not in the SN, despite a similar omega-3 depletion (~65%) in these regions. Increased lipoperoxidation and decreased catalase activity were found in both regions, while lower tSOD activity was observed only in the striatum. Fewer TH- (~40%) and BDNF-positive cells (~20%) were detected at the SN compared to the control. CONCLUSION: The present findings demonstrate a differential effect of omega-3 deficiency on NO production in the rat's nigrostriatal system. Prolonging omega-3 depletion until adulthood impaired striatum's anti-oxidant resources and BDNF distribution in the SN, worsening dopaminergic cell degeneration. GENERAL SIGNIFICANCE: Omega-3 deficiency can reduce the nigrostriatal system's ability to maintain homeostasis under oxidative conditions, which may enhance the risk of Parkinson's disease.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/fisiologia , Ácidos Graxos Ômega-3/fisiologia , Óxido Nítrico/biossíntese , Doença de Parkinson/etiologia , Substância Negra/fisiologia , Animais , Fator Neurotrófico Derivado do Encéfalo/análise , Catalase/metabolismo , Feminino , Peroxidação de Lipídeos , Masculino , Estresse Oxidativo , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Tirosina 3-Mono-Oxigenase/análiseRESUMO
Four suites of behavioral traits have been associated with four broad neural systems: the 1) dopamine and related norepinephrine system; 2) serotonin; 3) testosterone; 4) and estrogen and oxytocin system. A 56-item questionnaire, the Fisher Temperament Inventory (FTI), was developed to define four temperament dimensions associated with these behavioral traits and neural systems. The questionnaire has been used to suggest romantic partner compatibility. The dimensions were named: Curious/Energetic; Cautious/Social Norm Compliant; Analytical/Tough-minded; and Prosocial/Empathetic. For the present study, the FTI was administered to participants in two functional magnetic resonance imaging studies that elicited feelings of love and attachment, near-universal human experiences. Scores for the Curious/Energetic dimension co-varied with activation in a region of the substantia nigra, consistent with the prediction that this dimension reflects activity in the dopamine system. Scores for the Cautious/Social Norm Compliant dimension correlated with activation in the ventrolateral prefrontal cortex in regions associated with social norm compliance, a trait linked with the serotonin system. Scores on the Analytical/Tough-minded scale co-varied with activity in regions of the occipital and parietal cortices associated with visual acuity and mathematical thinking, traits linked with testosterone. Also, testosterone contributes to brain architecture in these areas. Scores on the Prosocial/Empathetic scale correlated with activity in regions of the inferior frontal gyrus, anterior insula and fusiform gyrus. These are regions associated with mirror neurons or empathy, a trait linked with the estrogen/oxytocin system, and where estrogen contributes to brain architecture. These findings, replicated across two studies, suggest that the FTI measures influences of four broad neural systems, and that these temperament dimensions and neural systems could constitute foundational mechanisms in personality structure and play a role in romantic partnerships.
Assuntos
Córtex Pré-Frontal/fisiologia , Substância Negra/fisiologia , Temperamento , Adulto , Idoso , Mapeamento Encefálico , Relações Familiares , Feminino , Humanos , Hipotálamo/fisiologia , Relações Interpessoais , Locus Cerúleo/fisiologia , Amor , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Modelos Psicológicos , Inventário de Personalidade , Reprodutibilidade dos Testes , Inquéritos e Questionários , Adulto JovemRESUMO
Studies have sought to assess various potential neuroprotective therapeutics in Parkinson's disease. The aim of this study was to evaluate the effects of static magnetic field stimulation 14 days after a 6-Hydroxydopamine (6-OHDA) substantia nigra compacta (SNc) lesion on motor behavior, as assessed by the rotarod (RR) test and brain tissue morphology. Forty male Wistar rats were used and were divided into five groups: control group, sham group (SG), lesion group (LG), lesion north pole group (LNPG) and lesion south pole group (LSPG). In groups with magnetic stimulation, a 3200-gauss magnet was fixed to the skull. After the experiments, the animals were anesthetized for brain perfusion. Coronal sections of the SNc were stained with Nissl. The RR test showed a decrease in the time spent on the apparatus in the LG compared with all groups. The LNPG and LSPG had significant increases in the time spent when compared to the LG. A morphometric analysis revealed a significant reduction in the number of neurons in the LG, LNPG and LSPG in relation to the SG. There were a higher number of neurons in the LNPG and LSPG than the LG, and a higher number of neurons in the LSPG than the LNPG. We observed that the LG, LNPG and LSPG showed a higher number of glial cells than the SG, and the LNPG and LSPG showed a lower number of glial cells than the LG. Our results demonstrate a potential therapeutic use of static magnetic fields for the preservation of motor behavior and brain morphology in the SNc after 14 days with 6-OHDA lesion.
Assuntos
Comportamento Animal/efeitos dos fármacos , Campos Magnéticos , Neurotoxinas/toxicidade , Oxidopamina/metabolismo , Oxidopamina/toxicidade , Substância Negra/efeitos dos fármacos , Animais , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Magnetoterapia , Masculino , Atividade Motora/efeitos dos fármacos , Neurônios/citologia , Neurônios/efeitos dos fármacos , Ratos , Ratos Wistar , Substância Negra/citologia , Substância Negra/fisiologiaRESUMO
To explore the handedness effects on phase asymmetries in deep gray matter of healthy adults by using magnetic susceptibility-weighted imaging (SWI) phase. Thirty left-handed (16 men, 14 women; age range, 20 to 57 years) and 30 age- and sex-matched right-handed (16 men, 14 women; age range, 20 to 58 years) healthy adults were examined at 3.0 T MRI. For each subject, phase values were detected in bilateral frontal white matters (FWM), caudate nucleus (CA), putamen (PU), globus pallidus (GP), thalamus (TH), red nucleus (RN) and substantia nigra (SN) on phase images. Statistical analysis was performed with paired-samples t-test and independent-samples t-test. In both handedness groups, the corrected phase values in the left hemisphere were significantly lower than those in the right one in FWM, CA, PU, GP (P < 0.05) and there was no significant hemispheric asymmetry in TH, RN and SN (P > 0.05). Differences in corrected phase values in corresponding brain regions of the same hemisphere between left-handed and right-handed groups were not statistically significant (P > 0.05). Hemispheric asymmetry of SWI phase in deep gray matter may not associate with handedness in adult brain.
Assuntos
Encéfalo/fisiologia , Lateralidade Funcional/fisiologia , Imageamento por Ressonância Magnética/métodos , Adulto , Gânglios da Base/fisiologia , Feminino , Lobo Frontal/fisiologia , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Núcleo Rubro/fisiologia , Substância Negra/fisiologia , Tálamo/fisiologia , Adulto JovemRESUMO
BACKGROUND: Responsive deep brain stimulation (rDBS) has been recently proposed to block epileptic seizures at onset. Yet, long-term stability of brain responses to such kind of stimulation is not known. OBJECTIVE: To quantify the neural adaptation to repeated rDBS as measured by the changes of anti-epileptic efficacy of bilateral DBS of the substantia nigra pars reticulata (SNr) versus auditory stimulation, in a rat model of spontaneous recurrent absence seizures (GAERS). METHODS: Local field potentials (LFP) were recorded in freely moving animals during 1 h up to 24 h under automated responsive stimulations (SNr-DBS and auditory). Comparison of seizure features was used to characterise transient (repetition-suppression effect) and long-lasting (stability of anti-epileptic efficacy, i.e. ratio of successfully interrupted seizures) effects of responsive stimulations. RESULTS: SNr-DBS was more efficient than auditory stimulation in blocking seizures (97% vs. 52% of seizures interrupted, respectively). Sensitivity to minimal interstimulus interval was much stronger for SNr-DBS than for auditory stimulation. Anti-epileptic efficacy of SNr-DBS was remarkably stable during long-term (24 h) recordings. CONCLUSIONS: In the GAERS model, we demonstrated the superiority of SNr-DBS to suppress seizures, as compared to auditory stimulation. Importantly, we found no long-term habituation to rDBS. However, when seizure recurrence was frequent, rDBS lack anti-epileptic efficacy because responsive stimulations became too close (time interval < 40 s) suggesting the existence of a refractory period. This study thus motivates the use of automated rDBS in patients having transient seizures separated by sufficiently long intervals.
Assuntos
Estimulação Acústica/métodos , Adaptação Fisiológica/fisiologia , Estimulação Encefálica Profunda/métodos , Epilepsia Tipo Ausência/fisiopatologia , Epilepsia Tipo Ausência/terapia , Substância Negra/fisiologia , Análise de Variância , Animais , Anticonvulsivantes/uso terapêutico , Modelos Animais de Doenças , Eletroencefalografia , Epilepsia Tipo Ausência/genética , Potenciais Evocados Auditivos/fisiologia , Masculino , Ratos , Fatores de TempoRESUMO
Activation of type 1 cannabinoid receptors (CB1R) decreases GABA and glutamate release in cortical and subcortical regions, with complex outcomes on cortical network activity. To date there have been few attempts to disentangle the region- and cell-specific mechanisms underlying the effects of cannabinoids on cortical network activity in vivo. Here we addressed this issue by combining in vivo electrophysiological recordings with local and systemic pharmacological manipulations in conditional mutant mice lacking CB1R expression in different neuronal populations. First we report that cannabinoids induce hypersynchronous thalamocortical oscillations while decreasing the amplitude of faster cortical oscillations. Then we demonstrate that CB1R at striatonigral synapses (basal ganglia direct pathway) mediate the thalamocortical hypersynchrony, whereas activation of CB1R expressed in cortical glutamatergic neurons decreases cortical synchrony. Finally we show that activation of CB1 expressed in cortical glutamatergic neurons limits the cannabinoid-induced thalamocortical hypersynchrony. By reporting that CB1R activations in cortical and subcortical regions have contrasting effects on cortical synchrony, our study bridges the gap between cellular and in vivo network effects of cannabinoids. Incidentally, the thalamocortical hypersynchrony we report suggests a potential mechanism to explain the sensory "high" experienced during recreational consumption of marijuana.
Assuntos
Canabinoides/farmacologia , Córtex Cerebral/citologia , Corpo Estriado/citologia , Neurônios GABAérgicos/metabolismo , Rede Nervosa/fisiologia , Receptor CB1 de Canabinoide/metabolismo , Animais , Córtex Cerebral/fisiologia , Corpo Estriado/fisiologia , Sincronização Cortical , Cicloexanóis , Eletromiografia , Ácido Glutâmico/metabolismo , Camundongos , Camundongos Mutantes , Rede Nervosa/efeitos dos fármacos , Piperidinas , Pirazóis , Receptor CB1 de Canabinoide/deficiência , Receptor CB1 de Canabinoide/genética , Estatísticas não Paramétricas , Substância Negra/fisiologia , Tálamo/fisiologiaRESUMO
BACKGROUND: Parkinson's disease (PD) is a degenerative brain disorder that is caused by neural defects in the substantia nigra. Numerous studies have reported that acupuncture treatment on GB34 (Yanglingquan) leads to significant improvements in patients with PD and in PD animal models. Studies using functional magnetic resonance imaging (fMRI) have shown that patients with PD, compared to healthy participants, have lower neural responses in extensive brain regions including the putamen, thalamus, and the supplementary motor area. OBJECTIVE: This study investigated the reported association between acupuncture point GB34 and PD. METHODS: Using fMRI, neural responses of 12 patients with PD and 12 healthy participants were examined before and after acupuncture stimulation. RESULTS: Acupuncture stimulation increased neural responses in regions including the substantia nigra, caudate, thalamus, and putamen, which are impaired caused by PD. CONCLUSIONS: Areas associated with PD were activated by the acupuncture stimulation on GB34. This shows that acupuncture treatment on GB34 may be effective in improving the symptoms of PD. Although more randomized controlled trials on the topic will be needed, this study shows that acupuncture may be helpful in the treatment of symptoms involving PD.
Assuntos
Terapia por Acupuntura , Mapeamento Encefálico , Encéfalo/fisiologia , Vias Neurais/fisiologia , Doença de Parkinson/terapia , Pontos de Acupuntura , Adulto , Idoso , Estudos de Casos e Controles , Núcleo Caudado/fisiologia , Potenciais Evocados/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Putamen/fisiologia , Valores de Referência , Substância Negra/fisiologia , Tálamo/fisiologiaRESUMO
In this study we have constructed a mathematical model of a recently proposed functional model known to be responsible for inducing waking, NREMS and REMS. Simulation studies using this model reproduced sleep-wake patterns as reported in normal animals. The model helps to explain neural mechanism(s) that underlie the transitions between wake, NREMS and REMS as well as how both the homeostatic sleep-drive and the circadian rhythm shape the duration of each of these episodes. In particular, this mathematical model demonstrates and confirms that an underlying mechanism for REMS generation is pre-synaptic inhibition from substantia nigra onto the REM-off terminals that project on REM-on neurons, as has been recently proposed. The importance of orexinergic neurons in stabilizing the wake-sleep cycle is demonstrated by showing how even small changes in inputs to or from those neurons can have a large impact on the ensuing dynamics. The results from this model allow us to make predictions of the neural mechanisms of regulation and patho-physiology of REMS.