Neuroscientist最新文献

High-grade gliomas (HGGs) are the commonest primary brain cancers. They are characterized by a pattern of aggressive growth and diffuse infiltration of the host brain that severely limits the efficacy of conventional treatments and patient outcomes, which remain generally poor. Recent work has described a suite of mechanisms via which HGGs interact, predominantly bidirectionally, with various cell types in the host brain including neurons, glial cells, immune cells, and vascular elements to drive tumor growth and invasion. These insights have the potential to inspire novel approaches to HGG therapy that are critically needed. This review explores HGG-host brain interactions and considers whether and how they might be exploited for therapeutic gain.

The vagus nerve, as an important component of the gut-brain axis, plays a crucial role in the communication between the gut and brain. It influences food intake, fat metabolism, and emotion by regulating the gut-brain axis, which is closely associated with the development of gastrointestinal, psychiatric, and metabolism-related disorders. In recent years, significant progress has been made in understanding the vagus-mediated regulatory pathway, highlighting its profound implications in the development of many diseases. Here, we summarize the latest advancements in vagus-mediated gut-brain pathways and the novel interventions targeting the vagus nerve. This will provide valuable insights for future research on treatment of obesity and gastrointestinal and depressive disorders based on vagus nerve stimulation.

Multiple cortical motor areas are critically involved in the voluntary control of discrete movement (e.g., reaching) and gait. Here, we outline experimental findings in nonhuman primates with clinical reports and research in humans that explain characteristic movement control mechanisms in the primary, supplementary, and presupplementary motor areas, as well as in the dorsal premotor area. We then focus on single-neuron activity recorded while monkeys performed motor sequences consisting of multiple discrete movements, and we consider how area-specific control mechanisms may contribute to the performance of complex movements. Following this, we explore the motor areas in cats that we have considered as analogs of those in primates based on similarities in their cortical surface topology, anatomic connections, microstimulation effects, and activity patterns. Emphasizing that discrete movement and gait modification entail similar control mechanisms, we argue that single-neuron activity in each area of the cat during gait modification is compatible with the function ascribed to the activity in the corresponding area in primates, recorded during the performance of discrete movements. The findings that demonstrate the premotor areas' contribution to locomotion, currently unique to the cat model, should offer highly valuable insights into the control mechanisms of locomotion in primates, including humans.

The current study investigates the intricate connection between neurology and islands shedding light on the historical, epidemiological, and genetic aspects. Based on an elaborate literature review, we identified neurological conditions having a significant clustering in an island(s), confined to a particular island(s), named after an island, and described first in an island. The genetic factors played a crucial role, uncovering disorders like Cayman ataxia, Machado Joseph disease, SGCE-mediated dystonia-myoclonus syndrome, X-linked dystonia parkinsonism, hereditary transthyretinrelated amyloidosis, Charcot Marie Tooth 4F, and progressive myoclonic epilepsy syndromes, that exhibited remarkable clustering in diverse islands. Local customs also left enduring imprints. Practices such as cannibalism in Papua New Guinea led to Kuru, while cycad seed consumption in Guam triggered Lytico-Bodig disease. Toxin-mediated neurologic disorders exhibited intricate island connections, exemplified by Minamata disease in Kyushu islands and atypical parkinsonism in French Caribbean islands. Additionally, the Cuban epidemic of amblyopia and neuropathy was associated with severe nutritional deficiencies. This study pioneers a comprehensive review narrating the genetic, environmental, and cultural factors highlighting the spectrum of neurological disorders in island settings. It enriches the medical literature with a unique understanding of the diverse influences shaping neurological health in island environments.

Spinal cord injury leads to disruption in autonomic control resulting in cardiovascular, bowel, and lower urinary tract dysfunctions, all of which significantly reduce health-related quality of life. Although spinal cord stimulation shows promise for promoting autonomic recovery, the underlying mechanisms are unclear. Based on current preclinical and clinical evidence, this narrative review provides the most plausible mechanisms underlying the effects of spinal cord stimulation for autonomic recovery, including activation of the somatoautonomic reflex and induction of neuroplastic changes in the spinal cord. Areas where evidence is limited are highlighted in an effort to guide the scientific community to further explore these mechanisms and advance the clinical translation of spinal cord stimulation for autonomic recovery.

The mesencephalic locomotor region (MLR) controls locomotion in vertebrates. In humans with Parkinson disease, locomotor deficits are increasingly associated with decreased activity in the MLR. This brainstem region, commonly considered to include the cuneiform and pedunculopontine nuclei, has been explored as a target for deep brain stimulation to improve locomotor function, but the results are variable, from modest to promising. However, the MLR is a heterogeneous structure, and identification of the best cell type to target is only beginning. Here, I review the studies that uncovered the role of genetically defined MLR cell types, and I highlight the cells whose activation improves locomotor function in animal models of Parkinson disease. The promising cell types to activate comprise some glutamatergic neurons in the cuneiform and caudal pedunculopontine nuclei, as well as some cholinergic neurons of the pedunculopontine nucleus. Activation of MLR GABAergic neurons should be avoided, since they stop locomotion or evoke bouts flanked with numerous stops. MLR is also considered a potential target in spinal cord injury, supranuclear palsy, primary progressive freezing of gait, or stroke. Better targeting of the MLR cell types should be achieved through optimized deep brain stimulation protocols, pharmacotherapy, or the development of optogenetics for human use.

The amygdala has long held the center seat in the neural basis of threat conditioning. However, a rapidly growing literature has elucidated extra-amygdala circuits in this process, highlighting the sensory cortex for its critical role in the mnemonic aspect of the process. While this literature is largely focused on the auditory system, substantial human and rodent findings on the olfactory system have emerged. The unique nature of the olfactory neuroanatomy and its intimate association with emotion compels a review of this recent literature to illuminate its special contribution to threat memory. Here, integrating recent evidence in humans and animal models, we posit that the olfactory (piriform) cortex is a primary and necessary component of the distributed threat memory network, supporting mnemonic ensemble coding of acquired threat. We further highlight the basic circuit architecture of the piriform cortex characterized by distributed, auto-associative connections, which is prime for highly efficient content-addressable memory computing to support threat memory. Given the primordial role of the piriform cortex in cortical evolution and its simple, well-defined circuits, we propose that olfaction can be a model system for understanding (transmodal) sensory cortical mechanisms underlying threat memory.

The brain is designed not only with molecules and cellular processes that help to form memories but also with molecules and cellular processes that suppress the formation and retention of memory. The latter processes are critical for an efficient memory management system, given the vast amount of information that each person experiences in their daily activities and that most of this information becomes irrelevant with time. Thus, efficiency dictates that the brain should have processes for selecting the most critical information for storage and suppressing the irrelevant or forgetting it later should it escape the initial filters. Such memory suppressor molecules and processes are revealed by genetic or pharmacologic insults that lead to enhanced memory expression. We review here the predominant memory suppressor molecules and processes that have recently been discovered. They are diverse, as expected, because the brain is complex and employs many different strategies and mechanisms to form memories. They include the gene-repressive actions of small noncoding RNAs, repressors of protein synthesis, cAMP-mediated gene expression pathways, inter- and intracellular signaling pathways for normal forgetting, and others. A deep understanding of memory suppressor molecules and processes is necessary to fully comprehend how the brain forms, stabilizes, and retrieves memories and to reveal how brain disorders disrupt memory.

Microglia are a specialized type of neuroimmune cells that undergo morphological and molecular changes through multiple signaling pathways in response to pathological protein aggregates, neuronal death, tissue injury, or infections. Microglia express Trem2, which serves as a receptor for a multitude of ligands enhancing their phagocytic activity. Trem2 has emerged as a critical modulator of microglial activity, especially in many neurodegenerative disorders. Human TREM2 mutations are associated with an increased risk of developing Alzheimer disease (AD) and other neurodegenerative diseases. Trem2 plays dual roles in neuroinflammation and more specifically in disease-associated microglia. Most recent developments on the molecular mechanisms of Trem2, emphasizing its role in uptake and clearance of amyloid β (Aβ) aggregates and other tissue debris to help protect and preserve the brain, are encouraging. Although Trem2 normally stimulates defense mechanisms, its dysregulation can intensify inflammation, which poses major therapeutic challenges. Recent therapeutic approaches targeting Trem2 via agonistic antibodies and gene therapy methodologies present possible avenues for reducing the burden of neurodegenerative diseases. This review highlights the promise of Trem2 as a therapeutic target, especially for Aβ-associated AD, and calls for more mechanistic investigations to understand the context-specific role of microglial Trem2 in developing effective therapies against neurodegenerative diseases.