Brain-resident macrophages, microglia, have been proposed to have an active role in synaptic refinement and maturation, influencing plasticity and circuit-level connectivity. Here we show that several neurodevelopmental processes previously attributed to microglia can proceed without them. Using a genetically modified mouse that lacks microglia (Csf1r), we find that intrinsic properties, synapse number and synaptic maturation are largely normal in the hippocampal CA1 region and somatosensory cortex at stages where microglia have been implicated. Seizure susceptibility and hippocampal-prefrontal cortex coherence in awake behaving animals, processes that are disrupted in mice deficient in microglia-enriched genes, are also normal. Similarly, eye-specific segregation of inputs into the lateral geniculate nucleus proceeds normally in the absence of microglia. Single-cell and single-nucleus transcriptomic analyses of neurons and astrocytes did not uncover any substantial perturbation caused by microglial absence. Thus, the brain possesses remarkable adaptability to execute developmental synaptic refinement, maturation and connectivity in the absence of microglia.
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http://dx.doi.org/10.1038/s41593-024-01833-x | DOI Listing |
Nat Neurosci
January 2025
Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK.
Brain-resident macrophages, microglia, have been proposed to have an active role in synaptic refinement and maturation, influencing plasticity and circuit-level connectivity. Here we show that several neurodevelopmental processes previously attributed to microglia can proceed without them. Using a genetically modified mouse that lacks microglia (Csf1r), we find that intrinsic properties, synapse number and synaptic maturation are largely normal in the hippocampal CA1 region and somatosensory cortex at stages where microglia have been implicated.
View Article and Find Full Text PDFCurr Top Behav Neurosci
January 2025
Department of Experimental Psychology, University of Oxford, Oxford, UK.
A decline in hippocampal function has long been associated with the progression of cognitive impairments in patients with Alzheimer's disease (AD). The disruption of hippocampal synaptic plasticity [primarily the reduction of long-term potentiation LTP] by excess production of soluble beta-amyloid (Aβ) has long been accepted as the mechanism by which AD pathology impairs memory, at least during the early stages of AD pathogenesis. However, the premise that hippocampal LTP underpins the formation of associative, long-term memories has been challenged.
View Article and Find Full Text PDFCogn Neurodyn
December 2024
State Key Laboratory for Strength and Vibration of Mechanical Structures, School of Aerospace Engineering, Xi'an Jiaotong University, No.28 Xianning West Road, Xi'an, 710049 People's Republic of China.
This research scrutinizes the simultaneous evolution of each layer within a multilayered complex neural network and elucidates the effect of synaptic plasticity on inter-layer dynamics. In the absence of synaptic plasticity, a predominant feedforward effect is observed, resulting in the manifestation of complete synchrony in deep networks, with each layer assuming a chimera state. A significant increase in the number of synchronized neurons is observed as the layers augment, culminating in complete synchronization in the deeper sections.
View Article and Find Full Text PDFEpilepsy Behav
December 2024
Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, Victoria, 3004, Australia; Department of Neurology, The Alfred Hospital, Melbourne, Victoria, 3004, Australia; Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Victoria, 3000, Australia.
Epilepsy continues to pose significant social and economic challenges on a global scale. Existing therapeutic approaches predominantly revolve around neurocentric mechanisms, and fail to control seizures in approximately one-third of patients. This underscores the pressing need for novel and complementary treatment approaches to address this gap.
View Article and Find Full Text PDFJ Neurochem
January 2025
Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Neuron-glia interactions are fundamental to the development and function of the nervous system. During development, glia, including astrocytes, microglia, and oligodendrocytes, influence neuronal differentiation and migration, synapse formation and refinement, and myelination. In the mature brain, glia are crucial for maintaining neural homeostasis, modulating synaptic activity, and supporting metabolic functions.
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