Neuron最新文献

Visual neuroscience benefits from high-quality datasets with neuronal responses to many images. Several neuroimaging datasets have been published in recent years, but no comparable dataset with spiking activity exists. Here, we introduce the THINGS ventral stream spiking dataset (TVSD). We extensively sampled neuronal activity in response to >25,000 natural images from the THINGS database in macaques, using high-channel-count implants in three key cortical regions: primary visual cortex (V1), V4, and the inferotemporal cortex. We showcase the utility of TVSD by using an artificial neural network to visualize the tuning of neurons. We also characterize the correlated fluctuations in activity within and between areas and demonstrate that these noise correlations are strongest between neurons with similar tuning. The TVSD allows researchers to answer many questions about neuronal tuning, analyze the interactions within and between cortical regions, and compare spiking activity in monkeys to human neuroimaging data.

Spinal cord injury (SCI) increasingly affects aged individuals, where functional impairment and mortality are highest. However, the aging-dependent mechanisms underpinning tissue damage remain elusive. Here, we find that natural killer-like T (NKLT) cells seed the intact aged human and murine spinal cord and multiply further after injury. NKLT cells accumulate in the spinal cord via C-X-C motif chemokine receptor 6 and ligand 16 signaling to clonally expand by engaging with major histocompatibility complex (MHC)-I-expressing myeloid cells. NKLT cells expressing natural killer cell granule protein 7 (Nkg7) disrupt myeloid-cell-dependent wound healing in the aged injured cord. Nkg7 deletion in mice curbs NKLT cell degranulation to normalize the myeloid cell phenotype, thus promoting tissue repair and axonal integrity. Monoclonal antibodies neutralizing CD8⁺ T cells after SCI enhance neurological recovery by promoting wound healing. Our results unveil a reversible role for NKG7⁺CD8⁺ NKLT cells in exacerbating tissue damage, suggesting a clinically relevant treatment for SCI.

Gamma-band oscillations (GBOs) in the primary somatosensory cortex (S1) play key roles in nociceptive processing. Yet, one crucial question remains unaddressed: what neuronal mechanisms underlie nociceptive-evoked GBOs? Here, we addressed this question using a range of somatosensory stimuli (nociceptive and non-nociceptive), neural recording techniques (electroencephalography in humans and silicon probes and calcium imaging in rodents), and optogenetics (alone or simultaneously with electrophysiology in mice). We found that (1) GBOs encoded pain intensity independent of stimulus intensity in humans, (2) GBOs in S1 encoded pain intensity and were triggered by spiking of S1 interneurons, (3) parvalbumin (PV)-positive interneurons preferentially tracked pain intensity, and critically, (4) PV S1 interneurons causally modulated GBOs and pain-related behaviors for both thermal and mechanical pain. These findings provide causal evidence that nociceptive-evoked GBOs preferentially encoding pain intensity are generated by PV interneurons in S1, thereby laying a solid foundation for developing GBO-based targeted pain therapies.

Autophagy is a conserved mechanism that degrades damaged or superfluous cellular contents and enables nutrient recycling under starvation conditions. Many neurodegeneration-associated proteins are autophagy substrates, and autophagy upregulation ameliorates disease in many animal models of neurodegeneration by enhancing the clearance of toxic proteins, proinflammatory molecules, and dysfunctional organelles. Autophagy inhibition also induces neuronal and glial senescence, a phenomenon that occurs with increasing age in non-diseased brains as well as in response to neurodegeneration-associated stresses. However, aging and many neurodegeneration-associated proteins and mutations impair autophagy. This creates a potentially detrimental feedback loop whereby the accumulation of these disease-associated proteins impairs their autophagic clearance, facilitating their further accumulation and aggregation. Thus, understanding how autophagy interacts with aging, senescence, and neurodegenerative diseases in a temporal, cellular, and genetic context is important for the future clinical application of autophagy-modulating therapies in aging and neurodegeneration.

The cognitive neuroscience of human aging seeks to identify neural mechanisms behind the commonalities and individual differences in age-related behavioral changes. This goal has been pursued predominantly through structural or "task-free" resting-state functional neuroimaging. The former has elucidated the material foundations of behavioral decline, and the latter has provided key insight into how functional brain networks change with age. Crucially, however, neither is able to capture brain activity representing specific cognitive processes as they occur. In contrast, task-based functional imaging allows a direct probe into how aging affects real-time brain-behavior associations in any cognitive domain, from perception to higher-order cognition. Here, we outline why task-based functional neuroimaging must move center stage to better understand the neural bases of cognitive aging. In turn, we sketch a multi-modal, behavior-first research framework that is built upon cognitive experimentation and emphasizes the importance of theory and longitudinal design.

Every cell in the body has a biological sex. The expansion of aging research to investigate female- and male-specific biology heralds a major advance for human health. Unraveling and harnessing mechanistic etiologies of sex differences may reveal new diagnostics and therapeutics for the aging brain.

As global life expectancy increases, age-related brain diseases such as stroke and dementia have become leading causes of death and disability. The aging of the neurovasculature is a critical determinant of brain aging and disease risk. Neurovascular cells are particularly vulnerable to aging, which induces significant structural and functional changes in arterial, venous, and lymphatic vessels. Consequently, neurovascular aging impairs oxygen and glucose delivery to active brain regions, disrupts endothelial transport mechanisms essential for blood-brain exchange, compromises proteostasis by reducing the clearance of potentially toxic proteins, weakens immune surveillance and privilege, and deprives the brain of key growth factors required for repair and renewal. In this review, we examine the effects of neurovascular aging on brain function and its role in stroke, vascular cognitive impairment, and Alzheimer's disease. Finally, we discuss key unanswered questions that must be addressed to develop neurovascular strategies aimed at promoting healthy brain aging.

Aging has a detrimental impact on white matter, resulting in reduced volume, compromised structural integrity of myelinated axons, and an increase in white matter hyperintensities. These changes are closely linked to cognitive decline and neurological disabilities. The deterioration of myelin and its diminished ability to regenerate as we age further contribute to the progression of neurodegenerative disorders. Understanding these changes is crucial for devising effective disease prevention strategies. Here, we will discuss the structural alterations in white matter that occur with aging and examine the cellular and molecular mechanisms driving these aging-related transformations. We highlight how the progressive disruption of white matter may initiate a self-perpetuating cycle of inflammation and neural damage.

DNA damage is a major risk factor for the decline of neuronal functions with age and in neurodegenerative diseases. While how DNA damage causes neurodegeneration is still being investigated, innovations over the past decade have provided significant insights into this issue. Breakthroughs in next-generation sequencing methods have begun to reveal the characteristics of neuronal DNA damage hotspots and the causes of DNA damage. Chromosome conformation capture-based approaches have shown that, while DNA damage and the ensuing cellular response alter chromatin topology, chromatin organization at damage sites also affects DNA repair outcomes in neurons. Additionally, neuronal activity results in the formation of programmed DNA breaks, which could burden DNA repair mechanisms and promote neuronal dysfunction. Finally, emerging evidence implicates DNA damage-induced inflammation as an important contributor to the age-related decline in neuronal functions. Together, these discoveries have ushered in a new understanding of the significance of genome maintenance for neuronal function.

Brain health is intimately connected to fluid flow dynamics that cleanse the brain of potentially harmful waste material. This system is regulated by vascular dynamics, the maintenance of perivascular spaces, neural activity during sleep, and lymphatic drainage in the meningeal layers. However, aging can impinge on each of these layers of regulation, leading to impaired brain cleansing and the emergence of various age-associated neurological disorders, including Alzheimer's and Parkinson's diseases. Understanding the intricacies of fluid flow regulation in the brain and how this becomes altered with age could reveal new targets and therapeutic strategies to tackle age-associated neurological decline.