RESUMO
Perceptual decisions should depend on sensory evidence. However, such decisions are also influenced by past choices and outcomes. These choice history biases may reflect advantageous strategies to exploit temporal regularities of natural environments. However, it is unclear whether and how observers can adapt their choice history biases to different temporal regularities, to exploit the multitude of temporal correlations that exist in nature. Here, we show that male mice adapt their perceptual choice history biases to different temporal regularities of visual stimuli. This adaptation was slow, evolving over hundreds of trials across several days. It occurred alongside a fast non-adaptive choice history bias, limited to a few trials. Both fast and slow trial history effects are well captured by a normative reinforcement learning algorithm with multi-trial belief states, comprising both current trial sensory and previous trial memory states. We demonstrate that dorsal striatal dopamine tracks predictions of the model and behavior, suggesting that striatal dopamine reports reward predictions associated with adaptive choice history biases. Our results reveal the adaptive nature of perceptual choice history biases and shed light on their underlying computational principles and neural correlates.
Assuntos
Comportamento de Escolha , Corpo Estriado , Dopamina , Animais , Masculino , Dopamina/metabolismo , Camundongos , Corpo Estriado/metabolismo , Corpo Estriado/fisiologia , Comportamento de Escolha/fisiologia , Camundongos Endogâmicos C57BL , Tomada de Decisões/fisiologia , Recompensa , Estimulação Luminosa , Percepção Visual/fisiologia , Reforço PsicológicoRESUMO
A large-scale biophysical network model for the isolated striatal body is developed to optimise potential intrastriatal deep brain stimulation applied to, e.g. obsessive-compulsive disorder. The model is based on modified Hodgkin-Huxley equations with small-world connectivity, while the spatial information about the positions of the neurons is taken from a detailed human atlas. The model produces neuronal spatiotemporal activity patterns segregating healthy from pathological conditions. Three biomarkers were used for the optimisation of stimulation protocols regarding stimulation frequency, amplitude and localisation: the mean activity of the entire network, the frequency spectrum of the entire network (rhythmicity) and a combination of the above two. By minimising the deviation of the aforementioned biomarkers from the normal state, we compute the optimal deep brain stimulation parameters, regarding position, amplitude and frequency. Our results suggest that in the DBS optimisation process, there is a clear trade-off between frequency synchronisation and overall network activity, which has also been observed during in vivo studies.
Assuntos
Estimulação Encefálica Profunda , Modelos Neurológicos , Estimulação Encefálica Profunda/métodos , Humanos , Corpo Estriado/fisiologia , Neurônios/fisiologia , Rede Nervosa/fisiologia , Transtorno Obsessivo-Compulsivo/terapia , Transtorno Obsessivo-Compulsivo/fisiopatologiaRESUMO
The anterior cingulate cortex (ACC) has been implicated across multiple highly specialized cognitive functions-including task engagement, motivation, error detection, attention allocation, value processing, and action selection. Here, we ask if ACC lesions disrupt task performance and firing in dorsomedial striatum (DMS) during the performance of a reward-guided decision-making task that engages many of these cognitive functions. We found that ACC lesions impacted several facets of task performance-including decreasing the initiation and completion of trials, slowing reaction times, and resulting in suboptimal and inaccurate action selection. Reductions in movement times towards the end of behavioral sessions further suggested attenuations in motivation, which paralleled reductions in directional action selection signals in the DMS that were observed later in recording sessions. Surprisingly, however, beyond altered action signals late in sessions-neural correlates in the DMS were largely unaffected, even though behavior was disrupted at multiple levels. We conclude that ACC lesions result in overall deficits in task engagement that impact multiple facets of task performance during our reward-guided decision-making task, which-beyond impacting motivated action signals-arise from dysregulated attentional signals in the ACC and are mediated via downstream targets other than DMS.
Assuntos
Corpo Estriado , Tomada de Decisões , Giro do Cíngulo , Neurônios , Recompensa , Giro do Cíngulo/fisiologia , Giro do Cíngulo/fisiopatologia , Animais , Masculino , Tomada de Decisões/fisiologia , Neurônios/fisiologia , Corpo Estriado/fisiologia , Corpo Estriado/fisiopatologia , Potenciais de Ação/fisiologia , Tempo de Reação/fisiologia , Motivação/fisiologia , Desempenho Psicomotor/fisiologiaRESUMO
The frontal cortex-striatum circuit plays a pivotal role in adaptive goal-directed behaviors. However, it remains unclear how decision-related signals are mediated through cross-regional transmission between the medial frontal cortex and the striatum by neuronal ensembles in making decision based on outcomes of past action. Here, we analyzed neuronal ensemble activity obtained through simultaneous multiunit recordings in the secondary motor cortex (M2) and dorsal striatum (DS) in rats performing an outcome-based left-or-right choice task. By adopting tensor component analysis (TCA), a single-trial-based unsupervised dimensionality reduction approach, for concatenated ensembles of M2 and DS neurons, we identified distinct three spatiotemporal neural dynamics (TCA components) at the single-trial level specific to task-relevant variables. Choice-position-selective neural dynamics reflected the positions chosen and was correlated with the trial-to-trial fluctuation of behavioral variables. Intriguingly, choice-pattern-selective neural dynamics distinguished whether the incoming choice was a repetition or a switch from the previous choice before a response choice. Other neural dynamics was selective to outcome and increased within-trial activity following response. Our results demonstrate how the concatenated ensembles of M2 and DS process distinct features of decision-related signals at various points in time. Thereby, the M2 and DS collaboratively monitor action outcomes and determine the subsequent choice, whether to repeat or switch, for action selection.
Assuntos
Comportamento de Escolha , Corpo Estriado , Tomada de Decisões , Neurônios , Animais , Masculino , Corpo Estriado/fisiologia , Tomada de Decisões/fisiologia , Comportamento de Escolha/fisiologia , Neurônios/fisiologia , Córtex Motor/fisiologia , Ratos , Ratos Long-Evans , Potenciais de Ação/fisiologia , Lobo Frontal/fisiologia , Vias Neurais/fisiologiaRESUMO
The balance between goal-directed and habitual control has been proposed to determine the flexibility of instrumental behaviour, in both humans and animals. This view is supported by neuroscientific studies that have implicated dissociable neural pathways in the ability to flexibly adjust behaviour when outcome values change. A previous Diffusion Tensor Imaging study provided preliminary evidence that flexible instrumental performance depends on the strength of parallel cortico-striatal white-matter pathways previously implicated in goal-directed and habitual control. Specifically, estimated white-matter strength between caudate and ventromedial prefrontal cortex correlated positively with behavioural flexibility, and posterior putamen-premotor cortex connectivity correlated negatively, in line with the notion that these pathways compete for control. However, the sample size of the original study was limited, and so far, there have been no attempts to replicate these findings. In the present study, we aimed to conceptually replicate these findings by testing a large sample of 205 young adults to relate cortico-striatal connectivity to performance on the slips-of-action task. In short, we found only positive neural correlates of goal-directed performance, including striatal connectivity (caudate and anterior putamen) with the dorsolateral prefrontal cortex. However, we failed to provide converging evidence for the existence of a neural habit system that puts limits on the capacity for flexible, goal-directed action. We discuss the implications of our findings for dual-process theories of instrumental action.
Assuntos
Corpo Estriado , Objetivos , Vias Neurais , Substância Branca , Humanos , Substância Branca/fisiologia , Substância Branca/diagnóstico por imagem , Substância Branca/anatomia & histologia , Masculino , Feminino , Adulto , Corpo Estriado/fisiologia , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/anatomia & histologia , Adulto Jovem , Vias Neurais/fisiologia , Adolescente , Córtex Cerebral/fisiologia , Córtex Cerebral/diagnóstico por imagem , Imagem de Tensor de Difusão/métodosRESUMO
The hippocampal-dependent memory system and striatal-dependent memory system modulate reinforcement learning depending on feedback timing in adults, but their contributions during development remain unclear. In a 2-year longitudinal study, 6-to-7-year-old children performed a reinforcement learning task in which they received feedback immediately or with a short delay following their response. Children's learning was found to be sensitive to feedback timing modulations in their reaction time and inverse temperature parameter, which quantifies value-guided decision-making. They showed longitudinal improvements towards more optimal value-based learning, and their hippocampal volume showed protracted maturation. Better delayed model-derived learning covaried with larger hippocampal volume longitudinally, in line with the adult literature. In contrast, a larger striatal volume in children was associated with both better immediate and delayed model-derived learning longitudinally. These findings show, for the first time, an early hippocampal contribution to the dynamic development of reinforcement learning in middle childhood, with neurally less differentiated and more cooperative memory systems than in adults.
Assuntos
Corpo Estriado , Hipocampo , Aprendizagem , Reforço Psicológico , Humanos , Criança , Hipocampo/fisiologia , Estudos Longitudinais , Feminino , Masculino , Corpo Estriado/fisiologia , Aprendizagem/fisiologia , Imageamento por Ressonância Magnética , Tomada de Decisões/fisiologia , Tempo de Reação/fisiologiaRESUMO
Environmental cues, through Pavlovian learning, become conditioned stimuli that invigorate and guide animals toward rewards. Dopamine (DA) neurons in the ventral tegmental area (VTA) and substantia nigra (SNc) are crucial for this process, via engagement of a reciprocally connected network with their striatal targets. Critically, it remains unknown how dopamine neuron activity itself engages dopamine signals throughout the striatum, across learning. Here, we investigated how optogenetic Pavlovian cue conditioning of VTA or SNc dopamine neurons directs cue-evoked behavior and shapes subregion-specific striatal dopamine dynamics. We used a fluorescent biosensor to monitor dopamine in the nucleus accumbens (NAc) core and shell, dorsomedial striatum (DMS), and dorsolateral striatum (DLS). We demonstrate spatially heterogeneous, learning-dependent dopamine changes across striatal regions. Although VTA stimulation-evoked robust dopamine release in NAc core, shell, and DMS, predictive cues preferentially recruited dopamine release in NAc core, starting early in training, and DMS, late in training. Negative prediction error signals, reflecting a violation in the expectation of dopamine neuron activation, only emerged in the NAc core and DMS. Despite the development of vigorous movement late in training, conditioned dopamine signals did not emerge in the DLS, even during Pavlovian conditioning with SNc dopamine neuron activation, which elicited robust DLS dopamine release. Together, our studies show a broad dissociation in the fundamental prediction and reward-related information generated by VTA and SNc dopamine neuron populations and signaled by dopamine across the striatum. Further, they offer new insight into how larger-scale adaptations across the striatal network emerge during learning to coordinate behavior.
Assuntos
Condicionamento Clássico , Corpo Estriado , Dopamina , Neurônios Dopaminérgicos , Área Tegmentar Ventral , Animais , Dopamina/metabolismo , Neurônios Dopaminérgicos/fisiologia , Neurônios Dopaminérgicos/metabolismo , Área Tegmentar Ventral/fisiologia , Área Tegmentar Ventral/metabolismo , Masculino , Corpo Estriado/metabolismo , Corpo Estriado/fisiologia , Camundongos , Condicionamento Clássico/fisiologia , Aprendizagem/fisiologia , Sinais (Psicologia) , Optogenética , Substância Negra/metabolismo , Substância Negra/fisiologia , Camundongos Endogâmicos C57BL , Núcleo Accumbens/metabolismo , Núcleo Accumbens/fisiologiaRESUMO
We used a step-wheel system to examine the activity of striatal projection neurons as mice practiced stepping on complexly arranged foothold pegs in this Ferris-wheel-like device to receive reward. Sets of dorsolateral striatal projection neurons were sensitive to specific parameters of repetitive motor coordination during the runs. They responded to combinations of the parameters of continuous movements (interval, phase, and repetition), forming "chunking responses"-some for combinations of these parameters across multiple body parts. Recordings in sensorimotor cortical areas exhibited notably fewer such responses but were documented for smaller neuron sets whose heterogeneity was significant. Striatal movement encoding via chunking responsivity could provide insight into neural strategies governing effective motor control by the striatum. It is possible that the striking need for external rhythmic cuing to allow movement sequences by Parkinson's patients could, at least in part, reflect dysfunction in such striatal coding.
Assuntos
Corpo Estriado , Movimento , Animais , Corpo Estriado/fisiologia , Camundongos , Movimento/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Neurônios/fisiologia , Periodicidade , Atividade Motora/fisiologiaRESUMO
Adolescent risk-taking has been attributed to earlier-developing motivational neurocircuitry that is poorly controlled by immature executive-control neurocircuitry. Functional magnetic resonance imaging findings of increased ventral striatum (VS) recruitment by reward prospects in adolescents compared to adults support this theory. Other studies found blunted VS recruitment by reward-predictive cues in adolescents compared to adults. Task features may explain this discrepancy but have never been systematically explored. Adolescents and adults performed a novel reward task that holds constant the expected value of all rewards but varies whether rewards are dependent on vigilance-intensive responding versus making a lucky choice during a relaxed response window. We examined group by sub-task contrast differences in activation of VS and more motoric regions of striatum in response to anticipatory cues. Reward anticipation in both task conditions activated portions of striatum in both groups. In voxel-wise comparison, adults showed greater anticipatory recruitment of VS in trials involving choice during a relaxed time window, not in the more vigilance-demanding trials as hypothesized. In accord with our hypotheses, however, adults showed greater activation in dorsal striatum and putamen volumes of interest during reward anticipation under vigilance-demanding conditions. Following trial outcome notifications, adolescents showed greater activation of the VS during reward notification but lower activation during loss notification. These data extend findings of cross-sectional age-group differences in incentive-anticipatory recruitment of striatum, by demonstrating in adults relatively greater recruitment of motor effector regions of striatum by attentional and motor demands.
Assuntos
Atenção , Corpo Estriado , Imageamento por Ressonância Magnética , Recompensa , Humanos , Adolescente , Masculino , Feminino , Imageamento por Ressonância Magnética/métodos , Atenção/fisiologia , Adulto Jovem , Adulto , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/fisiologia , Antecipação Psicológica/fisiologia , Sinais (Psicologia) , Mapeamento Encefálico/métodosRESUMO
Functional deficits in basal ganglia (BG) circuits contribute to cognitive and motor dysfunctions in alcohol use disorder. Chronic alcohol exposure alters synaptic function and neuronal excitability in the dorsal striatum, but it remains unclear how it affects BG output that is mediated by the substantia nigra pars reticulata (SNr). Here, we describe a neuronal subpopulation-specific synaptic organization of striatal and subthalamic (STN) inputs to the medial and lateral SNr. Chronic alcohol exposure (CIE) potentiated dorsolateral striatum (DLS) inputs but did not change dorsomedial striatum and STN inputs to the SNr. Chemogenetic inhibition of DLS direct pathway neurons revealed an enhanced role for DLS direct pathway neurons in execution of an instrumental lever-pressing task. Overall, we reveal a subregion-specific organization of striatal and subthalamic inputs onto the medial and lateral SNr and find that potentiated DLS-SNr inputs are accompanied by altered BG control of action execution following CIE.
Assuntos
Gânglios da Base , Corpo Estriado , Etanol , Plasticidade Neuronal , Substância Negra , Animais , Plasticidade Neuronal/efeitos dos fármacos , Gânglios da Base/fisiologia , Gânglios da Base/fisiopatologia , Substância Negra/efeitos dos fármacos , Substância Negra/fisiologia , Etanol/farmacologia , Corpo Estriado/fisiologia , Masculino , Camundongos , Neurônios/fisiologia , Neurônios/efeitos dos fármacos , Alcoolismo/fisiopatologia , Vias NeuraisRESUMO
Advancing our understanding of brain function and developing treatments for neurological diseases hinge on the ability to modulate neuronal groups in specific brain areas without invasive techniques. Here, we introduce Airy-beam holographic sonogenetics (AhSonogenetics) as an implant-free, cell type-specific, spatially precise, and flexible neuromodulation approach in freely moving mice. AhSonogenetics utilizes wearable ultrasound devices manufactured using 3D-printed Airy-beam holographic metasurfaces. These devices are designed to manipulate neurons genetically engineered to express ultrasound-sensitive ion channels, enabling precise modulation of specific neuronal populations. By dynamically steering the focus of Airy beams through ultrasound frequency tuning, AhSonogenetics is capable of modulating neuronal populations within specific subregions of the striatum. One notable feature of AhSonogenetics is its ability to flexibly stimulate either the left or right striatum in a single mouse. This flexibility is achieved by simply switching the acoustic metasurface in the wearable ultrasound device, eliminating the need for multiple implants or interventions. AhSonogentocs also integrates seamlessly with in vivo calcium recording via fiber photometry, showcasing its compatibility with optical modalities without cross talk. Moreover, AhSonogenetics can generate double foci for bilateral stimulation and alleviate motor deficits in Parkinson's disease mice. This advancement is significant since many neurological disorders, including Parkinson's disease, involve dysfunction in multiple brain regions. By enabling precise and flexible cell type-specific neuromodulation without invasive procedures, AhSonogenetics provides a powerful tool for investigating intact neural circuits and offers promising interventions for neurological disorders.
Assuntos
Holografia , Neurônios , Animais , Holografia/métodos , Camundongos , Neurônios/fisiologia , Dispositivos Eletrônicos Vestíveis , Ondas Ultrassônicas , Corpo Estriado/fisiologia , Encéfalo/fisiologiaRESUMO
Deepfakes are viral ingredients of digital environments, and they can trick human cognition into misperceiving the fake as real. Here, we test the neurocognitive sensitivity of 25 participants to accept or reject person identities as recreated in audio deepfakes. We generate high-quality voice identity clones from natural speakers by using advanced deepfake technologies. During an identity matching task, participants show intermediate performance with deepfake voices, indicating levels of deception and resistance to deepfake identity spoofing. On the brain level, univariate and multivariate analyses consistently reveal a central cortico-striatal network that decoded the vocal acoustic pattern and deepfake-level (auditory cortex), as well as natural speaker identities (nucleus accumbens), which are valued for their social relevance. This network is embedded in a broader neural identity and object recognition network. Humans can thus be partly tricked by deepfakes, but the neurocognitive mechanisms identified during deepfake processing open windows for strengthening human resilience to fake information.
Assuntos
Percepção da Fala , Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Percepção da Fala/fisiologia , Rede Nervosa/fisiologia , Córtex Auditivo/fisiologia , Voz/fisiologia , Corpo Estriado/fisiologiaRESUMO
Measuring the dynamic relationship between neuromodulators, such as dopamine, and neuronal action potentials is imperative to understand how these fundamental modes of neural signaling interact to mediate behavior. We developed methods to measure concurrently dopamine and extracellular action potentials (i.e., spikes) in monkeys. Standard fast-scan cyclic voltammetric (FSCV) electrochemical (EChem) and electrophysiological (EPhys) recording systems are combined and used to collect spike and dopamine signals, respectively, from an array of carbon fiber (CF) sensors implanted in the monkey striatum. FSCV requires the application of small voltages at the implanted sensors to measure redox currents generated from target molecules, such as dopamine. These applied voltages create artifacts at neighboring EPhys measurement sensors which may lead to misclassification of these signals as physiological spikes. Therefore, simple automated temporal interpolation algorithms were designed to remove these artifacts and enable accurate spike extraction. We validated these methods using simulated artifacts and demonstrated an average spike recovery rate of 84.5%. We identified and discriminated cell type-specific units in the monkey striatum that were shown to correlate to specific behavioral task parameters related to reward size and eye movement direction. Synchronously recorded spike and dopamine signals displayed contrasting relations to the task variables, suggesting a complex relationship between these two modes of neural signaling. Future application of our methods will help advance our understanding of the interactions between neuromodulator signaling and neuronal activity, to elucidate more detailed mechanisms of neural circuitry and plasticity mediating behaviors in health and in disease.
Assuntos
Potenciais de Ação , Fibra de Carbono , Dopamina , Macaca mulatta , Animais , Potenciais de Ação/fisiologia , Dopamina/metabolismo , Masculino , Neurônios/fisiologia , Neurônios/metabolismo , Eletrodos Implantados , Corpo Estriado/fisiologia , Corpo Estriado/metabolismo , Artefatos , Técnicas Eletroquímicas/métodos , Movimentos Oculares/fisiologia , RecompensaRESUMO
Greater exposure to stressors over the life course is believed to promote striatum-dependent over hippocampus-dependent learning and memory processes under stressful conditions. However, little research in this context has actually assessed lifetime stressor exposure and, moreover, it remains unknown whether greater cumulative lifetime stressor exposure exerts comparable effects on striatum-dependent learning and hippocampus-dependent learning in non-stressful contexts. To investigate this issue, we used the Stress and Adversity Inventory for Adults (Adult STRAIN) and Multicued Search Task to investigate the relation between cumulative lifetime stressor exposure and striatum-dependent stimulus-response learning and hippocampus-dependent contextual learning under non-stressful conditions among healthcare professionals (N = 205; 157 females, 48 males; Age: M = 34.23, SD 9.3, range 20-59 years). Individuals with moderate, but not low, cumulative lifetime stressor exposure exhibited impaired learning for stimulus-response associations. In contrast, learning for context associations was unrelated to participants' lifetime stressor exposure profiles. These results thus provide first evidence that cumulative lifetime stressor exposure may have negative consequences on human striatum-dependent stimulus-response learning under non-stressful environmental conditions.
Assuntos
Aprendizagem , Estresse Psicológico , Humanos , Masculino , Feminino , Adulto , Estresse Psicológico/fisiopatologia , Pessoa de Meia-Idade , Adulto Jovem , Aprendizagem/fisiologia , Hipocampo/fisiologia , Corpo Estriado/fisiologiaRESUMO
The neocortex and striatum are topographically organized for sensory and motor functions. While sensory and motor areas are lateralized for touch and motor control, respectively, frontal areas are involved in decision-making, where lateralization of function may be less important. This study contrasted the topographic precision of cell-type-specific ipsilateral and contralateral cortical projections while varying the injection site location in transgenic mice of both sexes. While sensory cortical areas had strongly topographic outputs to the ipsilateral cortex and striatum, they were weaker and not as topographically precise to contralateral targets. The motor cortex had somewhat stronger projections but still relatively weak contralateral topography. In contrast, frontal cortical areas had high degrees of topographic similarity for both ipsilateral and contralateral projections to the cortex and striatum. Corticothalamic organization is mainly ipsilateral, with weaker, more medial contralateral projections. Corticostriatal computations might integrate input outside closed basal ganglia loops using contralateral projections, enabling the two hemispheres to act as a unit to converge on one result in motor planning and decision-making.
Assuntos
Lobo Frontal , Camundongos Transgênicos , Córtex Motor , Vias Neurais , Córtex Somatossensorial , Animais , Córtex Motor/fisiologia , Masculino , Feminino , Camundongos , Córtex Somatossensorial/fisiologia , Lobo Frontal/fisiologia , Vias Neurais/fisiologia , Lateralidade Funcional/fisiologia , Corpo Estriado/fisiologiaRESUMO
A large body of evidence has shown that treatments that interfere with memory consolidation become ineffective when animals are subjected to an intense learning experience; this effect has been observed after systemic and local administration of amnestic drugs into several brain areas, including the striatum. However, the effects of amnestic treatments on the process of extinction after intense training have not been studied. Previous research demonstrated increased spinogenesis in the dorsomedial striatum, but not in the dorsolateral striatum after intense training, indicating that the dorsomedial striatum is involved in the protective effect of intense training. To investigate this issue, male Wistar rats, previously trained with low, moderate, or high levels of foot shock, were used to study the effect of tetrodotoxin inactivation of dorsomedial striatum on memory consolidation and subsequent extinction of inhibitory avoidance. Performance of the task was evaluated during seven extinction sessions. Tetrodotoxin produced a marked deficit of memory consolidation of inhibitory avoidance trained with low and moderate intensities of foot shock, but normal consolidation occurred when a relatively high foot shock was used. The protective effect of intense training was long-lasting, as evidenced by the high resistance to extinction exhibited throughout the extinction sessions. We discuss the possibility that increased dendritic spinogenesis in dorsomedial striatum may underly this protective effect, and how this mechanism may be related to the resilient memory typical of post-traumatic stress disorder (PTSD).
Assuntos
Aprendizagem da Esquiva , Corpo Estriado , Extinção Psicológica , Ratos Wistar , Tetrodotoxina , Animais , Masculino , Extinção Psicológica/efeitos dos fármacos , Extinção Psicológica/fisiologia , Ratos , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Corpo Estriado/fisiologia , Corpo Estriado/efeitos dos fármacos , Tetrodotoxina/farmacologia , Consolidação da Memória/efeitos dos fármacos , Consolidação da Memória/fisiologia , Amnésia/fisiopatologia , Amnésia/prevenção & controle , EletrochoqueRESUMO
Many self-motivated and goal-directed behaviours display highly flexible, approximately 4 hour ultradian (shorter than a day) oscillations. Despite lacking direct correspondence to physical cycles in the environment, these ultradian rhythms may be involved in optimizing functional interactions with the environment and reflect intrinsic neural dynamics. Current evidence supports a role of mesostriatal dopamine (DA) in the expression and propagation of ultradian rhythmicity, however, the biochemical processes underpinning these oscillations remain to be identified. Here, we use a mathematical model to investigate D2 autoreceptor-dependent DA self-regulation as the source of ultradian behavioural rhythms. DA concentration at the midbrain-striatal synapses is governed through a dual-negative feedback-loop structure, which naturally gives rise to rhythmicity. This model shows the propensity of striatal DA to produce an ultradian oscillation characterized by a flexible period that is highly sensitive to parameter variations. Circadian (approximately 24 hour) regulation consolidates the ultradian oscillations and alters their response to the phase-dependent, rapid-resetting effect of a transient excitatory stimulus. Within a circadian framework, the ultradian rhythm orchestrates behavioural activity and enhances responsiveness to an external stimulus. This suggests a role for the circadian-ultradian timekeeping hierarchy in governing organized behaviour and shaping daily experience through coordinating the motivation to engage in recurring, albeit not highly predictable events, such as social interactions.
Assuntos
Dopamina , Receptores de Dopamina D2 , Ritmo Ultradiano , Dopamina/metabolismo , Dopamina/fisiologia , Receptores de Dopamina D2/metabolismo , Ritmo Ultradiano/fisiologia , Animais , Modelos Neurológicos , Humanos , Ritmo Circadiano/fisiologia , Corpo Estriado/fisiologia , Corpo Estriado/metabolismo , Biologia ComputacionalRESUMO
The sense of agency varies as a function of arousal in negative emotional contexts. As yet, it is unknown whether the same is true for positive affect, and how inter-individual characteristics might predict these effects. Temporal binding, an implicit measure of the sense of agency, was measured in 59 participants before and after watching either an emotionally neutral film clip or a positive film clip with high or low arousal. Analyses included participants' individual differences in subjective affective ratings, physiological arousal (pupillometry, skin conductance, heart rate), striatal dopamine levels via eye blink rates, and psychopathy. Linear mixed models showed that sexual arousal decreased temporal binding whereas calm pleasure had no facilitation effect on binding. Striatal dopamine levels were positively linked whereas subjective and physiological arousal may be negatively associated with binding towards actions. Psychopathic traits reduced the effect of high arousal on binding towards actions. These results provide evidence that individual differences influence the extent to which the temporal binding is affected by high arousing states with positive valence.
Assuntos
Nível de Alerta , Individualidade , Humanos , Nível de Alerta/fisiologia , Masculino , Feminino , Adulto , Adulto Jovem , Resposta Galvânica da Pele/fisiologia , Dopamina/metabolismo , Emoções/fisiologia , Frequência Cardíaca/fisiologia , Corpo Estriado/metabolismo , Corpo Estriado/fisiologia , Piscadela/fisiologia , Adolescente , Afeto/fisiologiaRESUMO
The striatum plays a central role in directing many complex behaviors ranging from motor control to action choice and reward learning. In our study, we used 55 male CFW mice with rapid decay linkage disequilibrium to systematically mine the striatum-related behavioral functional genes by analyzing their striatal transcriptomes and 79 measured behavioral phenotypic data. By constructing a gene coexpression network, we clustered the genes into 13 modules, with most of them being positively correlated with motor traits. Based on functional annotations as well as Fisher's exact and hypergeometric distribution tests, brown and magenta modules were identified as core modules. They were significantly enriched for striatal-related functional genes. Subsequent Mendelian randomization analysis verified the causal relationship between the core modules and dyskinesia. Through the intramodular gene connectivity analysis, Adcy5 and Kcnma1 were identified as brown and magenta module hub genes, respectively. Knock outs of both Adcy5 and Kcnma1 lead to motor dysfunction in mice, and KCNMA1 acts as a risk gene for schizophrenia and smoking addiction in humans. We also evaluated the cellular composition of each module and identified oligodendrocytes in the striatum to have a positive role in motor regulation.
Assuntos
Adenilil Ciclases , Corpo Estriado , Animais , Camundongos , Masculino , Corpo Estriado/metabolismo , Corpo Estriado/fisiologia , Adenilil Ciclases/genética , Comportamento Animal/fisiologia , Redes Reguladoras de Genes/genética , TranscriptomaRESUMO
Coordinated multijoint limb and digit movements-"manual dexterity"-underlie both specialized skills (e.g., playing the piano) and more mundane tasks (e.g., tying shoelaces). Impairments in dexterous skill cause significant disability, as occurs with motor cortical injury, Parkinson's disease, and a range of other pathologies. Clinical observations, as well as basic investigations, suggest that corticostriatal circuits play a critical role in learning and performing dexterous skills. Furthermore, dopaminergic signaling in these regions is implicated in synaptic plasticity and motor learning. Nonetheless, the role of striatal dopamine signaling in skilled motor learning remains poorly understood. Here, we use fiber photometry paired with a genetically encoded dopamine sensor to investigate striatal dopamine release in both male and female mice as they learn and perform a skilled reaching task. Dopamine rapidly increases during a skilled reach and peaks near pellet consumption. In the dorsolateral striatum, dopamine dynamics are faster than in the dorsomedial and ventral striatum. Across training, as reaching performance improves, dopamine signaling shifts from pellet consumption to cues that predict pellet availability, particularly in medial and ventral areas of the striatum. Furthermore, performance prediction errors are present across the striatum, with reduced dopamine release after an unsuccessful reach. These findings show that dopamine dynamics during skilled motor behaviors change with learning and are differentially regulated across striatal subregions.