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1.
Psiquiatr. biol. (Internet) ; 27(2): 47-53, mayo-ago. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-193246

RESUMO

En la actualidad se defiende la interacción entre la cognición, la emoción y la motivación en el desarrollo de la alta capacidad intelectual; sin embargo, pocos son los estudios que describen los niveles de función corticales y subcorticales superpuestos para explicar su manifestación. Esta revisión pretende integrar los mecanismos neurobiológicos que facilitan la motivación y la práctica en los niños con altas capacidades durante las primeras fases de su aprendizaje. La alta sensibilidad al entorno parece estar relacionada con unas neuronas piramidales y espinosas más rápidas y eficientes, la detección y la búsqueda de la novedad con la actividad de los sistemas neuromoduladores dopaminérgicos, noradrenérgicos y glutamatérgicos en el hipocampo y el sistema mesolímbico, la mayor predisposición al desafío con un mayor número de conexiones en la corteza cingulada anterior, la motivación intrínseca y la perseverancia con la maduración precoz y la mayor plasticidad de las vías frontoparietales, frontoestriales y mesolímbicas


The interaction between cognition, emotion and motivation in giftedness development is currently advocated; however, few studies describe the levels of cortical and subcortical functions superimposed to explain their manifestation. This review aims to integrate neurobiological mechanisms that facilitate motivation and practice in giftedness children during the early stages of their learning. High sensitivity to the environment seems to be related to faster and more efficient pyramidal and spiny neurons, detection and search for novelty with the activity of the dopaminergic and noradrenergic neuromodulator systems in the hippocampus and the mesolimbic system, the greater predisposition to the challenge with a greater number of connections in the anterior cingulate cortex, the intrinsic motivation and the perseverance with the early maturation and greater plasticity of the frontoparietal, frontostriatal and mesolimbic net


Assuntos
Humanos , Criança , Motivação , Propriedade Intelectual , Cognição/fisiologia , Emoções/fisiologia , Neurobiologia , Neurônios Dopaminérgicos/fisiologia , Criança Superdotada/psicologia
2.
PLoS One ; 15(8): e0237032, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790683

RESUMO

The behavioral activation system (BAS) and the behavioral inhibition system (BIS) have been proposed to relate to stable traits that predict inter-individual differences in motivation. Prior reports point dopamine (DA) pathways, mainly including ventral tegmental area (VTA) and substantia nigra (SN), implicate in subserving reward-related functions associated with BAS and inhibitory functions related with BIS. However, as an important factor that affects DA releasing, it remains an open question whether the ovarian hormones may also be related to BIS/BAS. Here, to investigate effects of the estradiol (E2) and progesterone (PROG) on BIS/BAS and related DA pathways, we employed a BIS/BAS scale and the resting-state functional magnetic resonance imaging (fMRI) during the late follicular phase (FP) and the mid-luteal phase (LP). On the behavioral level, when women had high PROG levels, their E2 levels were found positively correlated with BIS scores, but those women whose PROG levels were low, their E2 levels were negative correlation with BIS scores. On the neural level, we demonstrated BAS was related with the VTA pathway, included brain reward regions of nucleus accumbens (NAc) and orbitofrontal cortex (OFC). Meanwhile, the BIS was correlated with the SN-dorsolateral prefrontal cortex (dlPFC) pathway. ROI-based resting-state functional connectivity (RSFC) analyses further revealed that, RSFC between the SN and dlPFC was modulated by ovarian hormones. With higher PROG levels, increased E2 levels among women were accompanied by stronger RSFC of the SN-dlPFC, but when PROG levels were low, E2 levels were negatively correlated with the SN-dlPFC RSFC. These findings revealed a combined enhancement effect of E2 and PROG on BIS, and the SN-dlPFC pathway was mainly involved in this process.


Assuntos
Encéfalo/fisiologia , Dopamina/fisiologia , Inibição Psicológica , Motivação/fisiologia , Ovário/fisiologia , Adulto , Afeto/fisiologia , Encéfalo/diagnóstico por imagem , Neurônios Dopaminérgicos/fisiologia , Estradiol/fisiologia , Feminino , Neuroimagem Funcional , Humanos , Imagem por Ressonância Magnética , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia , Progesterona/fisiologia , Psicofisiologia , Substância Negra/diagnóstico por imagem , Substância Negra/fisiologia , Área Tegmentar Ventral/diagnóstico por imagem , Área Tegmentar Ventral/fisiologia , Adulto Jovem
4.
Nat Commun ; 11(1): 3071, 2020 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-32555162

RESUMO

Unlimited access to calorie-dense, palatable food is a hallmark of Western societies and substantially contributes to the worldwide rise of metabolic disorders. In addition to promoting overconsumption, palatable diets dampen daily intake patterns, further augmenting metabolic disruption. We developed a paradigm to reveal differential timing in the regulation of food intake behavior in mice. While homeostatic intake peaks in the active phase, conditioned place preference and choice experiments show an increased sensitivity to overeating on palatable food during the rest phase. This hedonic appetite rhythm is driven by endogenous circadian clocks in dopaminergic neurons of the ventral tegmental area (VTA). Mice with disrupted clock function in the VTA lose their hedonic overconsumption rhythms without affecting homeostatic intake. These findings assign a functional role of VTA clocks in modulating palatable feeding behaviors and identify a potential therapeutic route to counteract hyperphagy in an obesogenic environment.


Assuntos
Ritmo Circadiano , Neurônios Dopaminérgicos/fisiologia , Comportamento Alimentar , Área Tegmentar Ventral/fisiologia , Animais , Apetite , Comportamento Animal , Comportamento de Escolha , Homeostase , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Oscilometria
5.
Nat Neurosci ; 23(8): 968-980, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32541962

RESUMO

The ventral tegmental area (VTA) is important for reward processing and motivation. The anatomic organization of neurotransmitter-specific inputs to the VTA remains poorly resolved. In the present study, we mapped the major neurotransmitter projections to the VTA through cell-type-specific retrograde and anterograde tracing. We found that glutamatergic inputs arose from a variety of sources and displayed some connectivity biases toward specific VTA cell types. The sources of GABAergic projections were more widespread, displayed a high degree of differential innervation of subregions in the VTA and were largely biased toward synaptic contact with local GABA neurons. Inactivation of GABA release from the two major sources, locally derived versus distally derived, revealed distinct roles for these projections in behavioral regulation. Optogenetic manipulation of individual distal GABAergic inputs also revealed differential behavioral effects. These results demonstrate that GABAergic projections to the VTA are a major contributor to the regulation and diversification of the structure.


Assuntos
Neurônios GABAérgicos/metabolismo , Transmissão Sináptica/fisiologia , Área Tegmentar Ventral/metabolismo , Animais , Condicionamento Clássico/fisiologia , Condicionamento Operante/fisiologia , Neurônios Dopaminérgicos/fisiologia , Medo/fisiologia , Feminino , Masculino , Camundongos , Atividade Motora/fisiologia , Vias Neurais/metabolismo , Optogenética , Recompensa , Autoestimulação
6.
Nat Commun ; 11(1): 3111, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32561725

RESUMO

Midbrain dopaminergic (DA) axons make long longitudinal projections towards the striatum. Despite the importance of DA striatal innervation, processes involved in establishment of DA axonal connectivity remain largely unknown. Here we demonstrate a striatal-specific requirement of transcriptional regulator Nolz1 in establishing DA circuitry formation. DA projections are misguided and fail to innervate the striatum in both constitutive and striatal-specific Nolz1 mutant embryos. The lack of striatal Nolz1 expression results in nigral to pallidal lineage conversion of striatal projection neuron subtypes. This lineage switch alters the composition of secreted factors influencing DA axonal tract formation and renders the striatum non-permissive for dopaminergic and other forebrain tracts. Furthermore, transcriptomic analysis of wild-type and Nolz1-/- mutant striatal tissue led to the identification of several secreted factors that underlie the observed guidance defects and proteins that promote DA axonal outgrowth. Together, our data demonstrate the involvement of the striatum in orchestrating dopaminergic circuitry formation.


Assuntos
Orientação de Axônios/fisiologia , Axônios/fisiologia , Corpo Estriado/crescimento & desenvolvimento , Neurônios Dopaminérgicos/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Animais , Carbocianinas/administração & dosagem , Corpo Estriado/diagnóstico por imagem , Embrião de Mamíferos , Feminino , Corantes Fluorescentes/administração & dosagem , Peptídeos e Proteínas de Sinalização Intracelular/genética , Microscopia Intravital , Camundongos Knockout , Técnicas Analíticas Microfluídicas , Microinjeções , Microscopia Confocal , Rede Nervosa/fisiologia , Proteínas do Tecido Nervoso/genética , Técnicas de Cultura de Tecidos
7.
PLoS Comput Biol ; 16(5): e1007465, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32453725

RESUMO

Decision making relies on adequately evaluating the consequences of actions on the basis of past experience and the current physiological state. A key role in this process is played by the basal ganglia, where neural activity and plasticity are modulated by dopaminergic input from the midbrain. Internal physiological factors, such as hunger, scale signals encoded by dopaminergic neurons and thus they alter the motivation for taking actions and learning. However, to our knowledge, no formal mathematical formulation exists for how a physiological state affects learning and action selection in the basal ganglia. We developed a framework for modelling the effect of motivation on choice and learning. The framework defines the motivation to obtain a particular resource as the difference between the desired and the current level of this resource, and proposes how the utility of reinforcements depends on the motivation. To account for dopaminergic activity previously recorded in different physiological states, the paper argues that the prediction error encoded in the dopaminergic activity needs to be redefined as the difference between utility and expected utility, which depends on both the objective reinforcement and the motivation. We also demonstrate a possible mechanism by which the evaluation and learning of utility of actions can be implemented in the basal ganglia network. The presented theory brings together models of learning in the basal ganglia with the incentive salience theory in a single simple framework, and it provides a mechanistic insight into how decision processes and learning in the basal ganglia are modulated by the motivation. Moreover, this theory is also consistent with data on neural underpinnings of overeating and obesity, and makes further experimental predictions.


Assuntos
Gânglios da Base/fisiologia , Comportamento de Escolha , Aprendizagem , Modelos Neurológicos , Motivação , Animais , Comportamento Animal , Simulação por Computador , Dopamina/fisiologia , Neurônios Dopaminérgicos/fisiologia , Humanos , Mesencéfalo/fisiologia , Camundongos , Vias Neurais/fisiologia , Reforço Psicológico , Recompensa
8.
J Neurosci ; 40(20): 3969-3980, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32277045

RESUMO

The amygdala is a brain area critical for the formation of fear memories. However, the nature of the teaching signal(s) that drive plasticity in the amygdala are still under debate. Here, we use optogenetic methods to investigate the contribution of ventral tegmental area (VTA) dopamine neurons to auditory-cued fear learning in male mice. Using anterograde and retrograde labeling, we found that a sparse and relatively evenly distributed population of VTA neurons projects to the basal amygdala (BA). In vivo optrode recordings in behaving mice showed that many VTA neurons, among them putative dopamine neurons, are excited by footshocks, and acquire a response to auditory stimuli during fear learning. Combined cfos imaging and retrograde labeling in dopamine transporter (DAT) Cre mice revealed that a large majority of BA projectors (>95%) are dopamine neurons, and that BA projectors become activated by the tone-footshock pairing of fear learning protocols. Finally, silencing VTA dopamine neurons, or their axon terminals in the BA during the footshock, reduced the strength of fear memory as tested 1 d later, whereas silencing the VTA-central amygdala (CeA) projection had no effect. Thus, VTA dopamine neurons projecting to the BA contribute to fear memory formation, by coding for the saliency of the footshock event and by signaling such events to the basal amygdala.SIGNIFICANCE STATEMENT Powerful mechanisms of fear learning have evolved in animals and humans to enable survival. During fear conditioning, a sensory cue, such as a tone (the conditioned stimulus), comes to predict an innately aversive stimulus, such as a mild footshock (the unconditioned stimulus). A brain representation of the unconditioned stimulus must act as a teaching signal to instruct plasticity of the conditioned stimulus representation in fear-related brain areas. Here we show that dopamine neurons in the VTA that project to the basal amygdala contribute to such a teaching signal for plasticity, thereby facilitating the formation of fear memories. Knowledge about the role of dopamine in aversively motivated plasticity might allow further insights into maladaptive plasticities that underlie anxiety and post-traumatic stress disorders in humans.


Assuntos
Tonsila do Cerebelo/fisiologia , Neurônios Dopaminérgicos/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Medo/fisiologia , Medo/psicologia , Aprendizagem/fisiologia , Área Tegmentar Ventral/fisiologia , Estimulação Acústica , Animais , Sinais (Psicologia) , Proteínas da Membrana Plasmática de Transporte de Dopamina , Fenômenos Eletrofisiológicos/fisiologia , Eletrochoque , Masculino , Camundongos , Neuroimagem
9.
Int J Mol Sci ; 21(7)2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32276415

RESUMO

Numerous studies highlighted the beneficial effects of the Mediterranean diet (MD) in maintaining health, especially during ageing. Even neurodegeneration, which is part of the natural ageing process, as well as the foundation of ageing-related neurodegenerative disorders like Alzheimer's and Parkinson's disease (PD), was successfully targeted by MD. In this regard, olive oil and its polyphenolic constituents have received increasing attention in the last years. Thus, this study focuses on two main olive oil polyphenols, hydroxytyrosol (HT) and oleuropein aglycone (OLE), and their effects on ageing symptoms with special attention to PD. In order to avoid long-lasting, expensive, and ethically controversial experiments, the established invertebrate model organism Caenorhabditis elegans was used to test HT and OLE treatments. Interestingly, both polyphenols were able to increase the survival after heat stress, but only HT could prolong the lifespan in unstressed conditions. Furthermore, in aged worms, HT and OLE caused improvements of locomotive behavior and the attenuation of autofluorescence as a marker for ageing. In addition, by using three different C. elegans PD models, HT and OLE were shown i) to enhance locomotion in worms suffering from α-synuclein-expression in muscles or rotenone exposure, ii) to reduce α-synuclein accumulation in muscles cells, and iii) to prevent neurodegeneration in α-synuclein-containing dopaminergic neurons. Hormesis, antioxidative capacities and an activity-boost of the proteasome & phase II detoxifying enzymes are discussed as potential underlying causes for these beneficial effects. Further biological and medical trials are indicated to assess the full potential of HT and OLE and to uncover their mode of action.


Assuntos
Acetatos/uso terapêutico , Monoterpenos Ciclopentânicos/uso terapêutico , Neurônios Dopaminérgicos/metabolismo , Doença de Parkinson/prevenção & controle , Álcool Feniletílico/análogos & derivados , Piranos/uso terapêutico , alfa-Sinucleína , Acetatos/farmacologia , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/efeitos dos fármacos , Monoterpenos Ciclopentânicos/farmacologia , Modelos Animais de Doenças , Neurônios Dopaminérgicos/fisiologia , Álcool Feniletílico/farmacologia , Álcool Feniletílico/uso terapêutico , Polifenóis/farmacologia , Piranos/farmacologia , Resultado do Tratamento
10.
Neuron ; 106(5): 778-788.e6, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32259476

RESUMO

Postingestive nutrient sensing can induce food preferences. However, much less is known about the ability of postingestive signals to modulate food-seeking behaviors. Here we report a causal connection between postingestive sucrose sensing and vagus-mediated dopamine neuron activity in the ventral tegmental area (VTA), supporting food seeking. The activity of VTA dopamine neurons increases significantly after administration of intragastric sucrose, and deletion of the NMDA receptor in these neurons, which affects bursting and plasticity, abolishes lever pressing for postingestive sucrose delivery. Furthermore, lesions of the hepatic branch of the vagus nerve significantly impair postingestive-dependent VTA dopamine neuron activity and food seeking, whereas optogenetic stimulation of left vagus nerve neurons significantly increases VTA dopamine neuron activity. These data establish a necessary role of vagus-mediated dopamine neuron activity in postingestive-dependent food seeking, which is independent of taste signaling.


Assuntos
Comportamento Apetitivo/efeitos dos fármacos , Neurônios Dopaminérgicos/fisiologia , Adoçantes Calóricos/administração & dosagem , Sacarose/administração & dosagem , Nervo Vago/fisiologia , Área Tegmentar Ventral/fisiologia , Animais , Comportamento Apetitivo/fisiologia , Condicionamento Operante , Alimentos , Camundongos , Camundongos Knockout , Plasticidade Neuronal/fisiologia , Adoçantes não Calóricos/administração & dosagem , Optogenética , Reforço Psicológico , Estômago , Sacarose/análogos & derivados , Canais de Cátion TRPM/genética , Paladar , Área Tegmentar Ventral/citologia
11.
Neuron ; 106(6): 977-991.e4, 2020 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-32289250

RESUMO

Forming long-term memory (LTM) often requires repetitive experience spread over time. Studies in Drosophila suggest aversive olfactory LTM is optimal after spaced training, multiple trials of differential odor conditioning with rest intervals. Memory after spaced training is frequently compared to that after the same number of trials without intervals. Here we show that, after spaced training, flies acquire additional information and form an aversive memory for the shock-paired odor and a slowly emerging and more persistent "safety-memory" for the explicitly unpaired odor. Safety-memory acquisition requires repetition, order, and spacing of the training trials and relies on triggering specific rewarding dopaminergic neurons. Co-existence of aversive and safety memories is evident as depression of odor-specific responses at different combinations of junctions in the mushroom body output network; combining two outputs appears to signal relative safety. Having complementary aversive and safety memories augments LTM performance after spaced training by making the odor preference more certain.


Assuntos
Aprendizagem da Esquiva/fisiologia , Condicionamento Clássico/fisiologia , Memória de Longo Prazo/fisiologia , Neurônios/fisiologia , Odorantes , Segurança , Animais , Neurônios Dopaminérgicos/fisiologia , Drosophila melanogaster , Corpos Pedunculados/fisiologia , Olfato , Fatores de Tempo
12.
Neuron ; 106(6): 1026-1043.e9, 2020 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-32294466

RESUMO

The central amygdala (CeA) orchestrates adaptive responses to emotional events. While CeA substrates for defensive behaviors have been studied extensively, CeA circuits for appetitive behaviors and their relationship to threat-responsive circuits remain poorly defined. Here, we demonstrate that the CeA sends robust inhibitory projections to the lateral substantia nigra (SNL) that contribute to appetitive and aversive learning in mice. CeA→SNL neural responses to appetitive and aversive stimuli were modulated by expectation and magnitude consistent with a population-level salience signal, which was required for Pavlovian conditioned reward-seeking and defensive behaviors. CeA→SNL terminal activation elicited reinforcement when linked to voluntary actions but failed to support Pavlovian associations that rely on incentive value signals. Consistent with a disinhibitory mechanism, CeA inputs preferentially target SNL GABA neurons, and CeA→SNL and SNL dopamine neurons respond similarly to salient stimuli. Collectively, our results suggest that amygdala-nigra interactions represent a previously unappreciated mechanism for influencing emotional behaviors.


Assuntos
Comportamento Apetitivo/fisiologia , Aprendizagem da Esquiva/fisiologia , Núcleo Central da Amígdala/fisiologia , Neurônios Dopaminérgicos/fisiologia , Neurônios GABAérgicos/fisiologia , Substância Negra/fisiologia , Animais , Condicionamento Clássico/fisiologia , Emoções , Camundongos , Vias Neurais , Reforço Psicológico , Recompensa , Substância Negra/citologia
13.
Neuron ; 106(3): 498-514.e8, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32145184

RESUMO

The brain dopamine (DA) system participates in forming and expressing memory. Despite a well-established role of DA neurons in the ventral tegmental area in memory formation, the exact DA circuits that control memory expression remain unclear. Here, we show that DA neurons in the dorsal raphe nucleus (DRN) and their medulla input control the expression of incentive memory. DRN DA neurons are activated by both rewarding and aversive stimuli in a learning-dependent manner and exhibit elevated activity during memory recall. Disrupting their physiological activity or DA synthesis blocks the expression of natural appetitive and aversive memories as well as drug memories associated with opioids. Moreover, a glutamatergic pathway from the lateral parabrachial nucleus to the DRN selectively regulates the expression of reward memories associated with opioids or foods. Our study reveals a specialized DA subsystem important for memory expression and suggests new targets for interventions against opioid addiction.


Assuntos
Neurônios Dopaminérgicos/fisiologia , Memória , Núcleos da Rafe/fisiologia , Recompensa , Animais , Dopamina/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Feminino , Ácido Glutâmico/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Morfina/farmacologia , Entorpecentes/farmacologia , Núcleos da Rafe/citologia , Núcleos da Rafe/metabolismo
14.
Nat Neurosci ; 23(4): 544-555, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32203499

RESUMO

Dopaminergic neurons (DANs) drive learning across the animal kingdom, but the upstream circuits that regulate their activity and thereby learning remain poorly understood. We provide a synaptic-resolution connectome of the circuitry upstream of all DANs in a learning center, the mushroom body of Drosophila larva. We discover afferent sensory pathways and a large population of neurons that provide feedback from mushroom body output neurons and link distinct memory systems (aversive and appetitive). We combine this with functional studies of DANs and their presynaptic partners and with comprehensive circuit modeling. We find that DANs compare convergent feedback from aversive and appetitive systems, which enables the computation of integrated predictions that may improve future learning. Computational modeling reveals that the discovered feedback motifs increase model flexibility and performance on learning tasks. Our study provides the most detailed view to date of biological circuit motifs that support associative learning.


Assuntos
Aprendizagem/fisiologia , Memória/fisiologia , Corpos Pedunculados/fisiologia , Animais , Neurônios Dopaminérgicos/fisiologia , Drosophila/fisiologia , Larva , Modelos Neurológicos , Vias Neurais/fisiologia
15.
J Neurosci ; 40(16): 3203-3216, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32209609

RESUMO

Giving birth triggers a wide repertoire of physiological and behavioral changes in the mother to enable her to feed and care for her offspring. These changes require coordination and are often orchestrated from the CNS, through as of yet poorly understood mechanisms. A neuronal population with a central role in puerperal changes is the tuberoinfundibular dopamine (TIDA) neurons that control release of the pituitary hormone, prolactin, which triggers key maternal adaptations, including lactation and maternal care. Here, we used Ca2+ imaging on mice from both sexes and whole-cell recordings on female mouse TIDA neurons in vitro to examine whether they adapt their cellular and network activity according to reproductive state. In the high-prolactin state of lactation, TIDA neurons shift to faster membrane potential oscillations, a reconfiguration that reverses upon weaning. During the estrous cycle, however, which includes a brief, but pronounced, prolactin peak, oscillation frequency remains stable. An increase in the hyperpolarization-activated mixed cation current, Ih, possibly through unmasking as dopamine release drops during nursing, may partially explain the reconfiguration of TIDA rhythms. These findings identify a reversible plasticity in hypothalamic network activity that can serve to adapt the dam for motherhood.SIGNIFICANCE STATEMENT Motherhood requires profound behavioral and physiological adaptations to enable caring for offspring, but the underlying CNS changes are poorly understood. Here, we show that, during lactation, neuroendocrine dopamine neurons, the "TIDA" cells that control prolactin secretion, reorganize their trademark oscillations to discharge in faster frequencies. Unlike previous studies, which typically have focused on structural and transcriptional changes during pregnancy and lactation, we demonstrate a functional switch in activity and one that, distinct from previously described puerperal modifications, reverses fully on weaning. We further provide evidence that a specific conductance (Ih) contributes to the altered network rhythm. These findings identify a new facet of maternal brain plasticity at the level of membrane properties and consequent ensemble activity.


Assuntos
Núcleo Arqueado do Hipotálamo/fisiologia , Neurônios Dopaminérgicos/fisiologia , Lactação/fisiologia , Rede Nervosa/fisiologia , Plasticidade Neuronal/fisiologia , Potenciais de Ação/fisiologia , Animais , Feminino , Masculino , Camundongos , Camundongos Transgênicos
16.
Sci Rep ; 10(1): 1838, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020036

RESUMO

The medial prefrontal cortex (mPFC) is a critical component of a cortico-basal ganglia-thalamo-cortical loop regulating limbic and cognitive functions. Within this circuit, two distinct nucleus accumbens (NAc) output neuron types, dopamine D1 or D2 receptor-expressing neurons, dynamically control the flow of information through basal ganglia nuclei that eventually project back to the mPFC to complete the loop. Thus, chronic dysfunction of the NAc may result in mPFC transcriptomal changes, which in turn contribute to disease conditions associated with the mPFC and basal ganglia. Here, we used RNA sequencing to analyse differentially expressed genes (DEGs) in the mPFC following a reversible neurotransmission blocking technique in D1 or D2 receptor-expressing NAc neurons, respectively (D1-RNB, or D2-RNB). Gene Set Enrichment Analysis revealed that gene sets of layer 5b and 6 pyramidal neurons were enriched in DEGs of the mPFC downregulated in both NAc D1- and D2-RNB mice. In contrast, gene sets of layer 5a pyramidal neurons were enriched in upregulated DEGs of the mPFC in D1-RNB mice, and downregulated DEGs of the mPFC in D2-RNB mice. These findings reveal for the first time that NAc output pathways play an important role in controlling mPFC gene expression.


Assuntos
Vias Neurais/metabolismo , Núcleo Accumbens/metabolismo , Córtex Pré-Frontal/metabolismo , Animais , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/fisiologia , Regulação da Expressão Gênica , Camundongos , Vias Neurais/fisiologia , Núcleo Accumbens/fisiologia , Células Piramidais/metabolismo , Células Piramidais/fisiologia , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Transcriptoma
17.
Science ; 367(6477): 549-555, 2020 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-32001651

RESUMO

Extinction learning allows animals to withhold voluntary actions that are no longer related to reward and so provides a major source of behavioral control. Although such learning is thought to depend on dopamine signals in the striatum, the way the circuits that mediate goal-directed control are reorganized during new learning remains unknown. Here, by mapping a dopamine-dependent transcriptional activation marker in large ensembles of spiny projection neurons (SPNs) expressing dopamine receptor type 1 (D1-SPNs) or 2 (D2-SPNs) in mice, we demonstrate an extensive and dynamic D2- to D1-SPN transmodulation across the striatum that is necessary for updating previous goal-directed learning. Our findings suggest that D2-SPNs suppress the influence of outdated D1-SPN plasticity within functionally relevant striatal territories to reshape volitional action.


Assuntos
Corpo Estriado/fisiologia , Neurônios Dopaminérgicos/fisiologia , Objetivos , Aprendizagem/fisiologia , Receptores de Dopamina D1/fisiologia , Receptores de Dopamina D2/fisiologia , Animais , Corpo Estriado/efeitos dos fármacos , Antagonistas de Dopamina/farmacologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nucleossomos/metabolismo , Racloprida/farmacologia , Receptores de Dopamina D1/antagonistas & inibidores
18.
Neuron ; 106(1): 142-153.e7, 2020 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-32027824

RESUMO

Dopamine neurons mediate the association of conditioned stimuli (CS) with reward (unconditioned stimuli, US) by signaling the discrepancy between predicted and actual reward during the US. Some theoretical models suggest that learning is also influenced by the salience or associability of the CS. A hallmark of CS associability models is that they can explain latent inhibition, i.e., the observation that novel CS are more effectively learned than familiar CS. Novel CS are known to activate dopamine neurons, but whether those responses affect associative learning has not been investigated. Here, we used fiber photometry to characterize dopamine responses to inconsequential familiar and novel stimuli. Using bidirectional optogenetic modulation during conditioning, we then show that CS-evoked dopamine promotes conditioned responses. This suggests that Pavlovian conditioning is influenced by CS dopamine, in addition to US reward prediction errors. Accordingly, the absence of dopamine responses to familiar CS might explain their slower learning in latent inhibition.


Assuntos
Aprendizagem por Associação/fisiologia , Condicionamento Clássico/fisiologia , Dopamina/metabolismo , Neurônios Dopaminérgicos/fisiologia , Parte Compacta da Substância Negra/metabolismo , Recompensa , Área Tegmentar Ventral/metabolismo , Animais , Sinais (Psicologia) , Neurônios Dopaminérgicos/metabolismo , Aprendizagem , Camundongos , Optogenética , Parte Compacta da Substância Negra/diagnóstico por imagem , Fotometria , Córtex Pré-Frontal , Terminações Pré-Sinápticas , Reconhecimento Psicológico , Área Tegmentar Ventral/diagnóstico por imagem
19.
PLoS One ; 15(2): e0229671, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32101569

RESUMO

As in vertebrates, dopaminergic neural systems are key regulators of motor programs in insects, including the fly Drosophila melanogaster. Dopaminergic systems innervate the Mushroom Bodies (MB), an important association area in the insect brain primarily associated to olfactory learning and memory, but that has been also implicated with the execution of motor programs. The main objectives of this work is to assess the idea that dopaminergic systems contribute to the execution of motor programs in Drosophila larvae, and then, to evaluate the contribution of specific dopaminergic receptors expressed in MB to these programs. Our results show that animals bearing a mutation in the dopamine transporter show reduced locomotion, while mutants for the dopaminergic biosynthetic enzymes or the dopamine receptor Dop1R1 exhibit increased locomotion. Pan-neuronal expression of an RNAi for the Dop1R1 confirmed these results. Further studies show that animals expressing the RNAi for Dop1R1 in the entire MB neuronal population or only in the MB γ-lobe forming neurons, exhibit an increased motor output, as well. Interestingly, our results also suggest that other dopaminergic receptors do not contribute to larval motor behavior. Thus, our data support the proposition that CNS dopamine systems innervating MB neurons modulate larval locomotion and that Dop1R1 mediates this effect.


Assuntos
Proteínas de Drosophila/metabolismo , Corpos Pedunculados/metabolismo , Receptores Dopaminérgicos/metabolismo , Animais , Aprendizagem da Esquiva/fisiologia , Condicionamento Clássico , Dopamina/metabolismo , Neurônios Dopaminérgicos/fisiologia , Proteínas de Drosophila/fisiologia , Drosophila melanogaster/metabolismo , Feminino , Regulação da Expressão Gênica/genética , Larva/genética , Larva/metabolismo , Locomoção/fisiologia , Masculino , Memória/fisiologia , Neurônios/metabolismo , Receptores Dopaminérgicos/fisiologia , Olfato/fisiologia
20.
Neural Netw ; 125: 10-18, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32070852

RESUMO

Recent findings suggest that acetylcholine mediates uncertainty-seeking behaviors through its projection to dopamine neurons - another neuromodulatory system known for its major role in reinforcement learning and decision-making. In this paper, we propose a leaky-integrate-and-fire model of this mechanism. It implements a softmax-like selection with an uncertainty bonus by a cholinergic drive to dopaminergic neurons, which in turn influence synaptic currents of downstream neurons. The model is able to reproduce experimental data in two decision-making tasks. It also predicts that: (i) in the absence of cholinergic input, dopaminergic activity would not correlate with uncertainty, and that (ii) the adaptive advantage brought by the implemented uncertainty-seeking mechanism is most useful when sources of reward are not highly uncertain. Moreover, this modeling work allows us to propose novel experiments which might shed new light on the role of acetylcholine in both random and directed exploration. Overall, this study contributes to a more comprehensive understanding of the role of the cholinergic system and, in particular, its involvement in decision-making.


Assuntos
Neurônios Colinérgicos/fisiologia , Tomada de Decisões , Neurônios Dopaminérgicos/fisiologia , Modelos Neurológicos , Redes Neurais de Computação , Incerteza , Acetilcolina/metabolismo , Animais , Neurônios Colinérgicos/metabolismo , Dopamina/fisiologia , Neurônios Dopaminérgicos/metabolismo , Humanos , Recompensa
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