Opportunities and limitations of genetically modified nonhuman primate models for neuroscience research

Proceedings of the National Academy of Sciences, Год журнала: 2020, Номер 117(39), С. 24022 - 24031

Опубликована: Авг. 19, 2020

The recently developed new genome-editing technologies, such as the CRISPR/Cas system, have opened door for generating genetically modified nonhuman primate (NHP) models basic neuroscience and brain disorders research. complex circuit formation experience-dependent refinement of human are very difficult to model in vitro, thus require use vivo whole-animal models. For many neurodevelopmental psychiatric disorders, abnormal might be at center their pathophysiology. Importantly, critical circuits regional cell populations implicated higher cognitive function not present lower mammalian brains, while these analogous areas replicated NHP brains. Indeed, neuropsychiatric represent a tremendous health economic burden globally. emerging field has potential transform our study dramatically facilitate development effective treatment disorders. In this paper, we discuss importance developing models, infrastructure training needed maximize impact ethical standards required using

Язык: Английский

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Dopamine blockade impairs the exploration-exploitation trade-off in rats

Scientific Reports, Год журнала: 2019, Номер 9(1)

Опубликована: Май 1, 2019

Abstract In a volatile environment where rewards are uncertain, successful performance requires delicate balance between exploitation of the best option and exploration alternative choices. It has theoretically been proposed that dopamine contributes to control this exploration-exploitation trade-off, specifically higher level tonic dopamine, more is favored. We demonstrate here there formal relationship rescaling positive reward prediction errors trade-off in simple non-stationary multi-armed bandit tasks. further show rats performing such task systemically antagonizing receptors greatly increases number random choices without affecting learning capacities. Simulations comparison set different computational models (an extended Q-learning model, directed meta-learning model) fitted on each individual confirm that, independently decreasing dopaminergic activity does not affect rate but equivalent an increase rate. This study shows could adapt decision-making when facing changing environmental contingencies.

Язык: Английский

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Neural circuits and activity dynamics underlying sex-specific effects of chronic social isolation stress

Cell Reports, Год журнала: 2021, Номер 34(12), С. 108874 - 108874

Опубликована: Март 1, 2021

Exposure to prolonged stress in critical developmental periods induces heightened vulnerability psychiatric disorders, which may have sex-specific consequences. Here we investigate the neuronal circuits mediating behavioral changes mice after chronic adolescent social isolation stress. Escalated aggression is exhibited stressed males, while withdrawal shown females. In vivo multichannel recordings of free-moving animals indicate that pyramidal neurons prefrontal cortex (PFC) from males exhibit significantly decreased spike activity during aggressive attacks, PFC females show a blunted increase discharge rates sociability tests. Chemogenetic and electrophysiological evidence shows hypofunctioning BLA principal neuron hyperactivity contribute elevated VTA dopamine hypoactivity diminished These results establish framework for understanding circuit physiological mechanisms underlying divergent effects

Язык: Английский

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Global reward state affects learning and activity in raphe nucleus and anterior insula in monkeys

Nature Communications, Год журнала: 2020, Номер 11(1)

Опубликована: Июль 28, 2020

Abstract People and other animals learn the values of choices by observing contingencies between them their outcomes. However, decisions are not guided choice-linked reward associations alone; macaques also maintain a memory general, average rate – global state in an environment. Remarkably, affects way that each choice outcome is valued influences future so impact both success failure different rich poor environments. Successful more likely to be repeated but this especially case Unsuccessful abandoned Functional magnetic resonance imaging (fMRI) revealed two distinct patterns activity, one anterior insula dorsal raphe nucleus, track as well specific events.

Язык: Английский

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Divergent Strategies for Learning in Males and Females

Current Biology, Год журнала: 2020, Номер 31(1), С. 39 - 50.e4

Опубликована: Окт. 30, 2020

A frequent assumption in value-based decision-making tasks is that agents make decisions based on the feature dimension reward probabilities vary on. However, complex, multidimensional environments, stimuli can multiple dimensions at once, meaning deserving most credit for outcomes not always obvious. As a result, individuals may strategies used to sample across dimensions, and these have an unrecognized influence decision-making. Sex proxy genetic endocrine influences behavior, including how environments are sampled. In this study, we examined adopted by female male mice as they learned value of varied both image location visually cued two-armed bandit, allowing two possible learn about. Female acquired correct image-value associations more quickly than mice, preferring fundamentally different strategy. were likely constrain their decision-space early learning preferentially sampling one over which images varied. Conversely, be inconsistent, changing choice frequently responding immediate experience stochastic rewards. Individual related sex-biased changes neuronal activation learning. Together, find sex associated with divergent about world, revealing substantial variability approaches implemented during decision making.

Язык: Английский

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Western Diet Consumption During Development: Setting the Stage for Neurocognitive Dysfunction

Frontiers in Neuroscience, Год журнала: 2021, Номер 15

Опубликована: Фев. 10, 2021

The dietary pattern in industrialized countries has changed substantially over the past century due to technological advances agriculture, food processing, storage, marketing, and distribution practices. availability of highly palatable, calorically dense foods that are shelf-stable facilitated a environment where overconsumption have high percentage calories derived from fat (particularly saturated fat) sugar is extremely common modern Westernized societies. In addition being predictor obesity metabolic dysfunction, consumption Western diet (WD) related poorer cognitive performance across lifespan. particular, WD during critical early life stages development negative consequences on various abilities later adulthood. This review highlights rodent model research identifying dietary, metabolic, neurobiological mechanisms linking periods (gestation, lactation, juvenile adolescence) with behavioral impairments multiple domains, including anxiety-like behavior, learning memory function, reward-motivated social behavior. literature supports which leads long-lasting neurocognitive largely dissociable effects dysfunction.

Язык: Английский

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Relationship between nuclei-specific amygdala connectivity and mental health dimensions in humans

Nature Human Behaviour, Год журнала: 2022, Номер 6(12), С. 1705 - 1722

Опубликована: Сен. 22, 2022

Язык: Английский

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Amygdala-cortical collaboration in reward learning and decision making

eLife, Год журнала: 2022, Номер 11

Опубликована: Сен. 5, 2022

Adaptive reward-related decision making requires accurate prospective consideration of the specific outcome each option and its current desirability. These mental simulations are informed by stored memories associative relationships that exist within an environment. In this review, I discuss recent investigations function circuitry between basolateral amygdala (BLA) lateral (lOFC) medial (mOFC) orbitofrontal cortex in learning use reward memories. draw conclusions from data collected using sophisticated behavioral approaches to diagnose content appetitive memory combination with modern circuit dissection tools. propose that, via their direct bidirectional connections, BLA OFC collaborate help us encode detailed, outcome-specific, state-dependent those enable predictions inferences support adaptive making. Whereas lOFC→BLA projections mediate encoding outcome-specific memories, mOFC→BLA regulate ability these inform pursuit decisions. lOFC mOFC both contribute guide The BLA→lOFC pathway mediates represent identity a predicted BLA→mOFC facilitates understanding value events. Thus, outline neuronal architecture for provide new testable hypotheses as well implications maladaptive

Язык: Английский

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Fear-Neuro-Inspired Reinforcement Learning for Safe Autonomous Driving

IEEE Transactions on Pattern Analysis and Machine Intelligence, Год журнала: 2023, Номер 46(1), С. 267 - 279

Опубликована: Окт. 6, 2023

Ensuring safety and achieving human-level driving performance remain challenges for autonomous vehicles, especially in safety-critical situations. As a key component of artificial intelligence, reinforcement learning is promising has shown great potential many complex tasks; however, its lack guarantees limits real-world applicability. Hence, further advancing learning, from the perspective, importance driving. revealed by cognitive neuroscientists, amygdala brain can elicit defensive responses against threats or hazards, which crucial survival adaptation to risky environments. Drawing inspiration this scientific discovery, we present fear-neuro-inspired framework realize safe through modeling functionality. This new technique facilitates an agent learn behaviors achieve decision making with fewer violations. Through experimental tests, show that proposed approach enables attain state-of-the-art compared baseline agents perform comparably 30 certified human drivers, across various scenarios. The results demonstrate feasibility effectiveness our while also shedding light on role simulating function application domains.

Язык: Английский

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Goal-directed learning in adolescence: neurocognitive development and contextual influences

Nature reviews. Neuroscience, Год журнала: 2024, Номер 25(3), С. 176 - 194

Опубликована: Янв. 23, 2024

Язык: Английский

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