Trends in Neurosciences最新文献

Reward processing is a critical brain function. Zichó and colleagues recently identified a previously unrecognized brainstem nucleus, the subventricular tegmental nucleus (SVTg), as a novel reward center that modulates dopamine release and regulates reward processing by balancing the lateral habenula (LHb)-ventral tegmental area (VTA) axis.

Hippocampal replay is widely thought to support two key cognitive functions: online decision-making and offline memory consolidation. In this review, we take a closer look at the hypothesized link between awake replay and online decision-making in rodents, and find only marginal evidence in support of this role. By contrast, the consolidation view is bolstered by new computational ideas and recent data, suggesting that (i) replay performs offline fictive learning for later goal-oriented behavior; and (ii) replay tags memories prior to sleep, prioritizing them for consolidation. Based on these recent advances, we favor an updated and refined role for awake replay - that is, supporting prioritized offline learning and tagging outside the hippocampus - rather than a direct, online role in guiding behavior.

Novel object recognition tasks are commonly used to assess memory in rodents. These tests rely on an innate preference for exploring objects that are new or have been moved or changed. However, this preference, while normally seen in control conditions, is not immutable. Stressful experiences as well as lesions and genetic mutations can lead mice and rats to show clear preferences for exploring familiar objects and familiar locations. This opinion article discusses the evidence for changes in novelty preference, implications of this lability for assessing memory, and the significance of shifts in novelty preference as a readout of changes in curiosity with implications in approach-avoidance behavior and explore-exploit decision-making. Finally, we provide some recommendations for reporting and interpreting novelty preference task findings moving forward.

How do neurons cope with chronic stress? In a recent study using blind Drosophila models, Shekhar and colleagues uncovered that chronic sensory deprivation induces brain-wide accumulation of aggregates sequestering transcription factors of the Integrated Stress Response (ISR). However, this protective mechanism prevents cells from triggering adapted transcriptional responses upon exogenous stress.

Chemotherapy treatment can significantly increase the survival of patients with cancer, but it also causes collateral damage in the body that can lead to treatment dose reductions and can reduce patient quality of life. One understudied side effect of chemotherapy is circadian disruption, which is associated with lasting biological and behavioral toxicities. Mechanisms of how chemotherapy alters circadian rhythms remain largely unknown, although leveraging rodent models may provide insights into causes and consequences of this disruption. Here, we review physiological, molecular, and behavioral evidence of central and peripheral circadian disruption in various rodent models of chemotherapy and discuss possible mechanisms driving these circadian disruptions. Overall, restoring circadian rhythms following treatment-induced disruptions may be a novel target by which to improve the health and quality of life of survivors.

Memory consolidation is thought to rely on the interplay of sleep-related brain oscillations. Drawing on recent findings that highlight the influence of respiration on these rhythms, we outline a framework positioning respiration as pacemaker for sleep's memory function. By orchestrating the cardinal non-rapid eye movement (NREM) oscillations, namely slow oscillations, spindles, and sharp wave-ripples, respiration may coordinate the hippocampo-cortical crosstalk essential for memory consolidation.

Despite extensive functional mapping studies using rodent functional magnetic resonance imaging (fMRI), interpreting the fMRI signals in relation to their neuronal origins remains challenging due to the hemodynamic nature of the response. Ultra high-resolution rodent fMRI, beyond merely enhancing spatial specificity, has revealed vessel-specific hemodynamic responses, highlighting the distinct contributions of intracortical arterioles and venules to fMRI signals. This 'single-vessel' fMRI approach shifts the paradigm of rodent fMRI, enabling its integration with other neuroimaging modalities to investigate neuro-glio-vascular (NGV) signaling underlying a variety of brain dynamics. Here, we review the emerging trend of combining multimodal fMRI with opto/chemogenetic neuromodulation and genetically encoded biosensors for cellular and circuit-specific recording, offering unprecedented opportunities for cross-scale brain dynamic mapping in rodent models.

Tau phosphorylation plays an essential role in regulating tau's microtubule-stabilizing function, but its hyperphosphorylation drives tauopathies such as Alzheimer's disease (AD). In a recent study, Kim and colleagues decipher that tyrosine kinase 2 (TYK2) phosphorylates tau at tyrosine 29, promoting its stabilization and aggregation by interfering with autophagic clearance, providing novel insights into tau pathology and potential therapeutic strategies.

Microglia are known to be involved in the modulation of amyloid-β (Aβ) plaques in Alzheimer's disease (AD). In a recent study, Jacquet et al. describe how microglia degrade larger Aβ aggregates by forming lysosomal synapses, further implicating the microglial release of lysosomal Aβ, amongst other processes, in the growth and spread of fibrillary Aβ.

The precise organization of the complex set of synaptic proteins at the nanometer scale is crucial for synaptic transmission. At the heart of this nanoscale architecture lies the nanocolumn. This aligns presynaptic neurotransmitter release with a high local density of postsynaptic receptor channels, thereby optimizing synaptic strength. Although synapses exhibit diverse protein compositions and nanoscale organizations, the role of structural diversity in the notable differences observed in synaptic physiology remains poorly understood. In this review we examine the current literature on the molecular mechanisms underlying the formation and maintenance of nanocolumns, as well as their role in modulating various aspects of synaptic transmission. We also discuss how the reorganization of nanocolumns contributes to functional dynamics in both synaptic plasticity and pathology.