Mitochondrial heterogeneity and homeostasis through the lens of a neuron

Nature Metabolism, Год журнала: 2022, Номер 4(7), С. 802 - 812

Опубликована: Июль 11, 2022

Язык: Английский

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Paying the brain's energy bill

Current Opinion in Neurobiology, Год журнала: 2022, Номер 78, С. 102668 - 102668

Опубликована: Дек. 24, 2022

How have animals managed to maintain metabolically expensive brains given the volatile and fleeting availability of calories in natural world? Here we review studies support three strategies that involve: 1) a reallocation energy from peripheral tissues functions cover costs brain, 2) an implementation energy-efficient neural coding, enabling brain operate at reduced costs, 3) efficient use costly resources during food scarcity. Collectively, these reveal heterogeneous set energy-saving mechanisms make energy-costly fit for survival.

Язык: Английский

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Lactate supply overtakes glucose when neural computational and cognitive loads scale up

Proceedings of the National Academy of Sciences, Год журнала: 2022, Номер 119(47)

Опубликована: Ноя. 14, 2022

Neural computational power is determined by neuroenergetics, but how and which energy substrates are allocated to various forms of memory engram unclear. To solve this question, we asked whether neuronal fueling glucose or lactate scales differently upon increasing neural computation cognitive loads. Here, using electrophysiology, two-photon imaging, tasks, mathematical modeling, show that both involved in formation, with supporting long-term synaptic plasticity evoked high-stimulation load activity patterns high attentional tasks being sufficient for less demanding learning tasks. Indeed, mandatory computation, such as theta-burst stimulation, while lighter activity-dependent potentiation (LTP), spike timing–dependent (STDP). We find subtle variations number frequency STDP shift the on-demand from lactate. Finally, demonstrate necessary a task requiring load, object-in-place task, corresponding vivo hippocampal LTP expression not needed simple novel object recognition. Overall, these results metabolism differentially engaged depending on complexity behavior.

Язык: Английский

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Mitochondrial fission drives neuronal metabolic burden to promote stress susceptibility in male mice

Nature Metabolism, Год журнала: 2023, Номер 5(12), С. 2220 - 2236

Опубликована: Ноя. 20, 2023

Язык: Английский

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Liraglutide restores impaired associative learning in individuals with obesity

Nature Metabolism, Год журнала: 2023, Номер 5(8), С. 1352 - 1363

Опубликована: Авг. 17, 2023

Survival under selective pressure is driven by the ability of our brain to use sensory information advantage control physiological needs. To that end, neural circuits receive and integrate external environmental cues internal metabolic signals form learned associations, consequently motivating adapting behaviour. The dopaminergic midbrain plays a crucial role in learning adaptive behaviour particularly sensitive peripheral signals, including intestinal peptides, such as glucagon-like peptide 1 (GLP-1). In single-blinded, randomized, controlled, crossover basic human functional magnetic resonance imaging study relying on computational model process underlying behavioural responses, we show reduced when sensing impaired obesity, indexed insulin sensitivity (participants: N = 30 with normal sensitivity; 24 sensitivity). Treatment GLP-1 receptor agonist liraglutide normalizes associations men women obesity. Collectively, findings reveal activation modulates associative people obesity via its central effects within mesoaccumbens pathway. These provide evidence for how can act neuromodulators adapt body's state agonists work clinics.

Язык: Английский

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Machine learning without a processor: Emergent learning in a nonlinear analog network

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(28)

Опубликована: Июль 2, 2024

Standard deep learning algorithms require differentiating large nonlinear networks, a process that is slow and power-hungry. Electronic contrastive local networks (CLLNs) offer potentially fast, efficient, fault-tolerant hardware for analog machine learning, but existing implementations are linear, severely limiting their capabilities. These systems differ significantly from artificial neural as well the brain, so feasibility utility of incorporating elements have not been explored. Here, we introduce CLLN—an electronic network made self-adjusting resistive based on transistors. We demonstrate system learns tasks unachievable in linear systems, including XOR (exclusive or) regression, without computer. find our decentralized reduces modes training error order (mean, slope, curvature), similar to spectral bias networks. The circuitry robust damage, retrainable seconds, performs learned microseconds while dissipating only picojoules energy across each transistor. This suggests enormous potential low-power computing edge like sensors, robotic controllers, medical devices, manufacturability at scale performing studying emergent learning.

Язык: Английский

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Thyroid hormone remodels cortex to coordinate body-wide metabolism and exploration

Cell, Год журнала: 2024, Номер 187(20), С. 5679 - 5697.e23

Опубликована: Авг. 22, 2024

Animals adapt to environmental conditions by modifying the function of their internal organs, including brain. To be adaptive, alterations in behavior must coordinated with functional state organs throughout body. Here, we find that thyroid hormone-a regulator metabolism many peripheral organs-directly activates cell-type-specific transcriptional programs frontal cortex adult male mice. These are enriched for axon-guidance genes glutamatergic projection neurons, synaptic regulatory both astrocytes and pro-myelination factors oligodendrocytes, suggesting widespread plasticity cortical circuits. Indeed, whole-cell electrophysiology revealed hormone alters excitatory inhibitory transmission, an effect requires hormone-induced gene presynaptic neurons. Furthermore, action regulates innate exploratory behaviors causally promotes decision-making. Thus, acts directly on cerebral males coordinate whole-body metabolic state.

Язык: Английский

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Cortical sensory processing across motivational states during goal-directed behavior

Neuron, Год журнала: 2022, Номер 110(24), С. 4176 - 4193.e10

Опубликована: Окт. 13, 2022

Behavioral states can influence performance of goal-directed sensorimotor tasks. Yet, it is unclear how altered neuronal sensory representations in these relate to task and learning. We trained water-restricted mice a two-whisker discrimination study cortical circuits underlying perceptual decision-making under different levels thirst. identified somatosensory cortices as well the premotor cortex part circuit necessary for execution. Two-photon calcium imaging areas populations selective or motor events. Analysis during individual sessions revealed distinct behavioral induced by decreasing thirst-related motivation. Learning was better explained improvements motivational state control rather than association. Whisker were across states. In particular, whisker stimuli could be decoded from activity high states, suggesting that state-dependent changes processing decision-making.

Язык: Английский

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Rationality, preferences, and emotions with biological constraints: it all starts from our senses

Trends in Cognitive Sciences, Год журнала: 2024, Номер 28(3), С. 264 - 277

Опубликована: Фев. 9, 2024

Is the role of our sensory systems to represent physical world as accurately possible? If so, are preferences and emotions, often deemed irrational, decoupled from these 'ground-truth' experiences? We show why answer both questions is 'no'. Brain function metabolically costly, brain loses some fraction information that it encodes transmits. Therefore, if brains maximize objective functions increase fitness their species, they should adapt objective-maximizing rules environment at earliest stages processing. Consequently, observed 'irrationalities', preferences, emotions stem necessity for early process while considering metabolic costs internal states organism.

Язык: Английский

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Human voltage-gated Na ⁺ and K ⁺ channel properties underlie sustained fast AP signaling

Science Advances, Год журнала: 2023, Номер 9(41)

Опубликована: Окт. 12, 2023

Human cortical pyramidal neurons are large, have extensive dendritic trees, and yet unexpectedly fast input-output properties: Rapid subthreshold synaptic membrane potential changes reliably encoded in timing of action potentials (APs). Here, we tested whether biophysical properties voltage-gated sodium (Na

Язык: Английский

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