Norepinephrine Signals Through Astrocytes To Modulate Synapses

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 22, 2024

Abstract Locus coeruleus (LC)-derived norepinephrine (NE) drives network and behavioral adaptations to environmental saliencies by reconfiguring circuit connectivity, but the underlying synapse-level mechanisms are elusive. Here, we show that NE remodeling of synaptic function is independent from its binding on neuronal receptors. Instead, astrocytic adrenergic receptors Ca 2+ dynamics fully gate effect synapses as astrocyte-specific deletion three astrocyte-silencing approaches all render insensitive NE. Additionally, find suppression strength results an ATP-derived adenosine A1 receptor-mediated control presynaptic efficacy. An accompanying study Chen et al. reveals existence analogous pathway in larval zebrafish highlights importance state transitions. Together, these findings fuel a new model wherein astrocytes core component neuromodulatory systems effector through which produces adaptations, challenging 80-year-old status quo.

Язык: Английский

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Playful brains: a possible neurobiological pathway to cognitive health in aging

Frontiers in Human Neuroscience, Год журнала: 2025, Номер 19

Опубликована: Фев. 7, 2025

Healthy cognitive aging emphasizes preserving functions essential for independence and well-being. Developing interventions that promote cognition resilience in older individuals is crucial. Social playfulness, characterized by spontaneity mutual enjoyment, allows to step away from routine roles engage novel surprising exchanges. Emerging evidence suggests social playfulness a promising approach supporting joyful engaging way. In this theory hypothesis manuscript, we propose neurobiological pathway mediating the effects of on cognition. Playful interactions generate high levels uncertainty, requiring continuous adaptation exploration. We suggest these demands locus coeruleus-noradrenaline (LC-NA) system, which crucial navigating uncertainty sustaining arousal flexibility needed adapt dynamic unpredictable nature playful interactions. Importantly, collaborative safe environment transforms uncertainty-driven noradrenergic activation into an rewarding experience, enhancing focus, positive affect, flexibility. adults, where LC-NA functionality may decline with age, could counteract upregulating system. review linking integrity health explore how might mitigate deterioration functioning training executive promoting novelty This framework bridges neuroscience, psychology, creative-arts therapies, highlighting as tool healthy aging. emphasize need further research validate its implications designing leverage enhance populations.

Язык: Английский

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Thalamocortical architectures for flexible cognition and efficient learning

Trends in Cognitive Sciences, Год журнала: 2024, Номер 28(8), С. 739 - 756

Опубликована: Июнь 17, 2024

The brain exhibits a remarkable ability to learn and execute context-appropriate behaviors. How it achieves such flexibility, without sacrificing learning efficiency, is an important open question. Neuroscience, psychology, engineering suggest that reusing repurposing computations are part of the answer. Here, we review evidence thalamocortical architectures may have evolved facilitate these objectives flexibility efficiency by coordinating distributed computations. Recent work suggests prefrontal cortical networks compute with flexible codes, mediodorsal thalamus provides regularization promote efficient reuse. Thalamocortical interactions resemble hierarchical Bayesian computations, their network implementation can be related existing gating, synchronization, hub theories thalamic function. By reviewing recent findings providing novel synthesis, highlight key research horizons integrating computation, cognition, systems neuroscience.

Язык: Английский

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Norepinephrine changes behavioral state via astroglial purinergic signaling

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 23, 2024

Both neurons and glia communicate via diffusible neuromodulatory substances, but the substrates of computation in such networks are unclear. During behavioral transitions larval zebrafish, neuromodulator norepinephrine drives fast excitation delayed inhibition behavior circuit activity. We find that inhibitory arm this feedforward motif is implemented by astroglial purinergic signaling. Neuromodulator imaging, pharmacology, perturbations astroglia reveal triggers release adenosine triphosphate, extracellular conversion into adenosine, suppression through activation hindbrain neuronal receptors. This work, along with a companion piece Lefton colleagues demonstrating an analogous pathway mediating effect on synaptic connectivity mice, identifies computational role for evolutionarily conserved signaling axis norepinephrine-mediated brain state transitions.

Язык: Английский

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Event boundaries drive norepinephrine release and distinctive neural representations of space in the rodent hippocampus

Опубликована: Янв. 31, 2025

Episodic memories are temporally segmented around event boundaries that tend to coincide with moments of environmental change. During these times, the state brain should change rapidly, or reset, ensure information encountered before and after an boundary is encoded in different neuronal populations. Norepinephrine (NE) thought facilitate this network reorganization. However, it unknown whether drive NE release hippocampus and, if so, how relates changes hippocampal firing patterns. The advent new GRAB sensor now allows for measurement binding sub-second resolution. Using tool mice, we tested released into dorsal during defined by unexpected transitions between spatial contexts presentations novel objections. We found dynamics were well explained time elapsed each changes, not related conditioned behaviors, exploratory bouts movement, reward. Familiarity a context accelerated rate which phasic decayed baseline. Knowing when elevated, coding space differs moments. Immediately observed relatively unique patterns neural spiking settled modal at similar returned These results consistent model wherein drives representations away from steady-state attractor. hypothesize distinctive codes may long-term memory contribute basis primacy effect.

Язык: Английский

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Event boundaries drive norepinephrine release and distinctive neural representations of space in the rodent hippocampus

Опубликована: Янв. 31, 2025

Episodic memories are temporally segmented around event boundaries that tend to coincide with moments of environmental change. During these times, the state brain should change rapidly, or reset, ensure information encountered before and after an boundary is encoded in different neuronal populations. Norepinephrine (NE) thought facilitate this network reorganization. However, it unknown whether drive NE release hippocampus and, if so, how relates changes hippocampal firing patterns. The advent new GRAB sensor now allows for measurement binding sub-second resolution. Using tool mice, we tested released into dorsal during defined by unexpected transitions between spatial contexts presentations novel objections. We found dynamics were well explained time elapsed each changes, not related conditioned behaviors, exploratory bouts movement, reward. Familiarity a context accelerated rate which phasic decayed baseline. Knowing when elevated, coding space differs moments. Immediately observed relatively unique patterns neural spiking settled modal at similar returned These results consistent model wherein drives representations away from steady-state attractor. hypothesize distinctive codes may long-term memory contribute basis primacy effect.

Язык: Английский

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Enhanced Working Memory Representations for Rare Events

Psychophysiology, Год журнала: 2025, Номер 62(3)

Опубликована: Март 1, 2025

ABSTRACT Rare events ( oddballs ) produce a variety of enhanced physiological responses relative to frequent standards ), including the P3b component event‐related potential (ERP) waveform. Previous research has suggested that is related working memory, which implies memory representations will be for rare stimuli. To test this hypothesis, we devised modified oddball paradigm where target disk was presented at one 16 different locations, were divided into and sets. Participants made binary response on each trial report whether appeared in set or set. As expected, much larger stimuli appearing location within We also included occasional probe trials subject reported exact target. Accuracy higher than locations. In addition, reports more accurate participants with amplitudes (although not participants). applied multivariate pattern analysis ERP data “decode” remembered Decoding accuracy greater locations then replicated extended our behavioral findings follow‐up experiment. These electrophysiological results demonstrate although both are stored performance events.

Язык: Английский

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Neuron-astrocyte coupling in lateral habenula mediates depressive-like behaviors

Cell, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

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A rat model of volitional mutual social interactions

Neuropsychopharmacology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 25, 2025

Язык: Английский

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Subcortical nuclei of the human ascending arousal system encode anticipated reward but do not predict subsequent memory

Cerebral Cortex, Год журнала: 2025, Номер 35(5)

Опубликована: Апрель 10, 2025

Abstract Subcortical nuclei of the ascending arousal system (AAS) play an important role in regulating brain and cognition. However, functional MRI (fMRI) these humans involves unique challenges due to their size location deep within brain. Here, we used ultra-high-field other methodological advances investigate activity 6 subcortical during reward anticipation memory encoding: locus coeruleus (LC), basal forebrain, median dorsal raphe nuclei, substantia nigra, ventral tegmental area. Participants performed a monetary incentive delay task, which successfully induced state anticipation, 24-h delayed surprise test. Region-of-interest analyses revealed that all increased potential rewards as opposed neutral outcomes. In contrast, none predicted performance 24 h later. These findings provide new insights into cognitive functions are supported by human AAS.

Язык: Английский

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