Trends in Neurosciences最新文献

Quiescence is a prolonged but reversible state of cell-cycle arrest that is an adaptive feature of most adult stem cell populations. In the brain, quiescence helps to protect adult neural stem cells from stress and supports lifelong neurogenesis. Unfortunately however, entry into a quiescent or a slow-cycling state is also a malignant feature of brain cancer stem cells. In glioblastoma, where the process has been best characterised, quiescent glioma stem cells preferentially survive chemoradiation, and after therapy, reactivate to regrow the tumour and drive recurrence. In this Review, we discuss the in vitro and in vivo models that have been developed for studying neural stem cell quiescence and how these tools may be used to deepen biological understanding and to develop novel therapies targeting quiescent glioma stem cells.

The parabrachial nucleus (PBN) in the dorsal pons responds to bodily threats and transmits alarm signals to the forebrain. Parabrachial neuron activity is enhanced during chronic pain, and inactivation of PBN neurons in mice prevents the establishment of neuropathic, chronic pain symptoms. Chemogenetic or optogenetic activation of all glutamatergic neurons in the PBN, or just the subpopulation that expresses the Calca gene, is sufficient to establish pain phenotypes, including long-lasting tactile allodynia, that scale with the extent of stimulation, thereby promoting nociplastic pain, defined as diffuse pain without tissue inflammation or nerve injury. This review focuses on the role(s) of molecularly defined PBN neurons and the downstream nodes in the brain that contribute to establishing nociplastic pain.

The maturation of cerebral cortical networks during early life involves a major reorganization of long-range axonal connections. In a recent study, Bragg-Gonzalo, Aguilera, et al. discovered that in mice, the interhemispheric connections sent by S1L4 callosal projection neurons are pruned via the tight control of their ipsilateral synaptic integration, which relies on the early activity of specific interneurons.

Traumatic brain injury (TBI) is a complex condition that can resolve over time but all too often leads to persistent symptoms, and the risk of poor patient outcomes increases with aging. TBI damages neurons and long axons within white matter tracts that are critical for communication between brain regions; this causes slowed information processing and neuronal circuit dysfunction. This review focuses on white matter injury after TBI and the multifactorial processes that underlie white matter damage, potential for recovery, and progression of degeneration. A multiscale perspective across clinical and preclinical advances is presented to encourage interdisciplinary insights from whole-brain neuroimaging of white matter tracts down to cellular and molecular responses of axons, myelin, and glial cells within white matter tissue.

Marked dysregulation of the human prefrontal cortex (PFC) and anterior cingulate cortex (ACC) characterises a variety of anxiety disorders, and its amelioration is a key feature of treatment success. Overall treatment response, however, is highly variable, and about a third of patients are resistant to treatment. In this review we hypothesise that a major contributor to this variation in treatment response are the multiple faces of anxiety induced by distinct forms of frontal cortex dysregulation. Comparison of findings from humans and non-human primates reveals marked similarity in the functional organisation of threat regulation across the frontal lobes. This organisation is discussed in relation to the 'predatory imminence continuum' model of threat and the differential engagement of executive functions at the core of both emotion generation and regulation strategies.

In the nervous system, G protein-coupled receptors (GPCRs) control neuronal excitability, synaptic transmission, synaptic plasticity, and, ultimately, behavior through spatiotemporally precise initiation of a variety of signaling pathways. However, despite their critical importance, there is incomplete understanding of how these receptors are regulated to tune their signaling to specific neurophysiological contexts. A deeper mechanistic picture of neuromodulatory GPCR function is needed to fully decipher their biological roles and effectively harness them for the treatment of neurological and psychiatric disorders. In this review, we highlight recent progress in identifying novel modes of regulation of neuromodulatory GPCRs, including G protein- and receptor-targeting mechanisms, receptor-receptor crosstalk, and unique features that emerge in the context of chemical synapses. These emerging principles of neuromodulatory GPCR tuning raise critical questions to be tackled at the molecular, cellular, synaptic, and neural circuit levels in the future.

Functional network (FN) analyses play a pivotal role in uncovering insights into brain function and understanding the pathophysiology of various brain disorders. This paper focuses on classical and advanced methods for deriving brain FNs from functional magnetic resonance imaging (fMRI) data. We systematically review their foundational principles, advantages, shortcomings, and interrelations, encompassing both static and dynamic FN extraction approaches. In the context of static FN extraction, we present hypothesis-driven methods such as region of interest (ROI)-based approaches as well as data-driven methods including matrix decomposition, clustering, and deep learning. For dynamic FN extraction, both window-based and windowless methods are surveyed with respect to the estimation of time-varying FN and the subsequent computation of FN states. We also discuss the scope of application of the various methods and avenues for future improvements.

Exposure to outdoor air pollution has been linked to adverse health effects, including potential widespread impacts on the CNS. Ongoing brain development may render children and adolescents especially vulnerable to neurotoxic effects of air pollution. While mechanisms remain unclear, promising advances in human neuroimaging can help elucidate both sensitive periods and neurobiological consequences of exposure to air pollution. Herein we review the potential influences of air pollution exposure on neurodevelopment, drawing from animal toxicology and human neuroimaging studies. Due to ongoing cellular and system-level changes during childhood and adolescence, the developing brain may be more sensitive to pollutants' neurotoxic effects, as a function of both timing and duration, with relevance to cognition and mental health. Building on these foundations, the emerging field of environmental neuroscience is poised to further decipher which air toxicants are most harmful and to whom.