Reorganization of adolescent prefrontal cortex circuitry is required for mouse cognitive maturation

Neuron, Год журнала: 2023, Номер 112(3), С. 421 - 440.e7

Опубликована: Ноя. 17, 2023

Most cognitive functions involving the prefrontal cortex emerge during late development. Increasing evidence links this delayed maturation to protracted timeline of development, which likely does not reach full maturity before end adolescence. However, underlying mechanisms that drive emergence and fine-tuning abilities adolescence, caused by circuit wiring, are still unknown. Here, we continuously monitored activity throughout postnatal development mice showed an initial increase was interrupted extensive microglia-mediated breakdown activity, followed rewiring elements achieve adult-like patterns synchrony. Interfering with these processes but adulthood, led a long-lasting microglia-induced disruption neuronal morphology decreased abilities. These results identified nonlinear reorganization circuits adolescence revealed its importance for adult network function processing.

Язык: Английский

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Pregnancy-induced maternal microchimerism shapes neurodevelopment and behavior in mice

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Авг. 5, 2022

Abstract Life-long brain function and mental health are critically determined by developmental processes occurring before birth. During mammalian pregnancy, maternal cells transferred to the fetus. They referred as microchimeric (MMc). Among other organs, MMc seed into fetal brain, where their is unknown. Here, we show that, in offspring’s developing mice, express a unique signature of sensome markers, control microglia homeostasis prevent excessive presynaptic elimination. Further, facilitate oscillatory entrainment prefrontal-hippocampal circuits support maturation behavioral abilities. Our findings highlight that not mere placental leak out, but rather functional mechanism shapes optimal conditions for healthy later life.

Язык: Английский

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Chronic exposure of alcohol triggers microglia-mediated synaptic elimination inducing cognitive impairment

Experimental Neurology, Год журнала: 2022, Номер 353, С. 114061 - 114061

Опубликована: Апрель 1, 2022

Язык: Английский

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IL-4 shapes microglia-dependent pruning of the cerebellum during postnatal development

Neuron, Год журнала: 2023, Номер 111(21), С. 3435 - 3449.e8

Опубликована: Ноя. 1, 2023

Interleukin-4 (IL-4) is a type 2 cytokine with pleiotropic functions in adaptive immunity, allergies, and cognitive processes. Here, we show that low levels of IL-4 the early postnatal stage delineate critical period which microglia extensively prune cerebellar neurons. Elevating this via peripheral injection, or using mouse model allergic asthma, leads to defective pruning, permanent increase granule cells, circuit alterations. These animals also hyperkinetic impulsive-like phenotype, reminiscent attention-deficit hyperactivity disorder (ADHD). alterations are blocked Il4rαfl/fl::Cx3cr1-CreER mice, deficient receptor signaling microglia. findings demonstrate previously unknown role for during neuroimmune maturation provide first putative mechanism comorbidity between disease ADHD observed humans.

Язык: Английский

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Neuronal coupling modes show differential development in the early cortical activity networks of human newborns

Journal of Neuroscience, Год журнала: 2024, Номер 44(26), С. e1012232024 - e1012232024

Опубликована: Май 20, 2024

The third trimester is a critical period for the development of functional networks that support lifelong neurocognitive performance, yet emergence neuronal coupling in these poorly understood. Here, we used longitudinal high-density electroencephalographic recordings from preterm infants during 33 to 45 weeks conceptional age (CA) characterize early spatiotemporal patterns local cortical function and intrinsic modes [ICMs; phase–phase (PPCs), amplitude–amplitude (AACs), phase–amplitude correlations (PACs)]. Absolute power showed robust increase with CA across full frequency spectrum, while PACs sleep state-specific, biphasic peaked few before normal birth. AACs distant decreased globally at nearly all frequencies. In contrast, PPCs frequency- region-selective development, an strength between frontal, central, occipital regions low-delta alpha frequencies together wider-spread decrease other Our findings present spectrally spatially differential distinct ICMs neonatal provide their developmental templates future basic clinical research.

Язык: Английский

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The Emerging Role of Microglia in Neuromyelitis Optica

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Фев. 19, 2021

Neuromyelitis optica (NMO) is an autoantibody-triggered neuro-inflammatory disease which preferentially attacks the spinal cord and optic nerve. Its defining autoantibody specific for water channel protein, aquaporin-4 (AQP4), primarily localized at end-feet of astrocytes. Histopathology studies early NMO lesions demonstrated prominent activation microglia, resident immune sentinels central nervous system (CNS). Significant microglial reactivity also observed in animal models induced by introducing AQP4-IgG into CNS. Here we review potential roles human patients as well different NMO. We will focus on molecular mechanisms underlying function microglia-astrocyte interaction pathogenesis. Understanding role microglia pathology may yield novel therapeutic approaches this disease.

Язык: Английский

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Active Dendrites and Local Field Potentials: Biophysical Mechanisms and Computational Explorations

Neuroscience, Год журнала: 2021, Номер 489, С. 111 - 142

Опубликована: Сен. 8, 2021

Neurons and glial cells are endowed with membranes that express a rich repertoire of ion channels, transporters, receptors. The constant flux ions across the neuronal results in voltage fluctuations can be recorded from extracellular matrix. high frequency components this signal contain information about spiking activity, reflecting output neurons surrounding recording location. low signal, referred to as local field potential (LFP), have been traditionally thought provide synaptic inputs impinge on large dendritic trees various neurons. In review, we discuss recent computational experimental studies pointing critical role several active mechanisms influence genesis location-dependent spectro-temporal dynamics LFPs, spanning different brain regions. We strongly emphasize need account for fast slow events associated — including gradients their expression profiles, inter- intra-cellular spatio-temporal interactions glia, heterogeneities degeneracy scales, neuromodulatory influences, activitydependent plasticity towards gaining important insights origins LFP under behavioral states health disease. simple but essential guidelines how model LFPs taking into these mechanisms, detailed methodology electrophysiological properties synapses while studying LFPs.

Язык: Английский

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Complement and microglia dependent synapse elimination in brain development

WIREs Mechanisms of Disease, Год журнала: 2021, Номер 14(3)

Опубликована: Ноя. 4, 2021

Abstract Synapse elimination, also known as synaptic pruning, is a critical step in the maturation of neural circuits during brain development. Mounting evidence indicates that complement cascade innate immune system plays an important role synapse elimination. Studies indicate excess synapses development are opsonized by proteins and subsequently phagocytosed microglia which expresses receptors. The process regulated diverse molecular signals, including inhibitors affect activation complement, well signals microglial recruitment activation. These may promote or inhibit removal specific sets complement‐microglia has been implicated pathogenesis several developmental disorders, suggesting dysregulation mechanisms pruning underlie circuitry defects these diseases. Here, we review latest on cellular complement‐dependent microglia‐dependent elimination development, highlight potential this therapeutic target for disorders. This article categorized under: Neurological Diseases > Molecular Cellular Physiology Stem Cells Development Immune System

Язык: Английский

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The Logic of Developing Neocortical Circuits in Health and Disease

Journal of Neuroscience, Год журнала: 2021, Номер 41(5), С. 813 - 822

Опубликована: Янв. 11, 2021

The sensory and cognitive abilities of the mammalian neocortex are underpinned by intricate columnar laminar circuits formed from an array diverse neuronal populations. One approach to determining how interactions between these circuit components give rise complex behavior is investigate rules which cortical acquire functionality during development. This review summarizes recent research on development neocortex, genetic determination in neural stem cells through dynamic role that specific populations play earliest they contribute emergent function cognition. While many endeavors take advantage model systems, consideration will also be given advances our understanding activity nascent human circuits. Such cross-species perspective imperative when investigating mechanisms underlying dysfunction early neocortical neurodevelopmental disorders, so one can identify targets amenable therapeutic intervention.

Язык: Английский

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Astrocytes lure CXCR2-expressing CD4 ⁺ T cells to gray matter via TAK1-mediated chemokine production in a mouse model of multiple sclerosis

Proceedings of the National Academy of Sciences, Год журнала: 2021, Номер 118(8)

Опубликована: Фев. 17, 2021

Significance Multiple sclerosis (MS) is a chronic neurological disease characterized by demyelination and neuronal damage. While T cells are consistently detected in the gray matter of human MS samples, they rarely seen most common mouse model MS. Here, we show modified that high degree damage, cell infiltration, reactive gliosis spinal cord matter. Using conditional knockout mice, migration to depends on expression CXCR2 astrocyte TAK1-mediated chemokines such as CXCL1.

Язык: Английский

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