Regulation of synaptic connectivity by glia.

“A recent study showed that the classical complement cascade, which is part of the innate immune system, helps to mediate synapse elimination in the developing CN”

“Recent gene-expression analysis of astrocytes in vivo showed that astrocytes produce messenger RNAs that encode several synaptic adhesion proteins, such as neurexins, neuroligins and cadherin”

“The extensive structural and functional association of perisynaptic glia with the synapse gave rise to the concept of the 'tripartite synapse', in which synapses are defined as comprising the presynaptic and postsynaptic specializations of the neurons and the glial process that ensheaths the”

“Interestingly, even though TNF-α increased the cell-surface expression of AMPA receptors, long-term potentiation and long-term depression were not affected in its absenc”

“For example, the human brain contains several more populations of astrocytes than the rodent brain, and human astrocytes are up to threefold larger and more ramified than their rodent counterpart”

“Under these conditions, RGCs show little spontaneous synapse activity and form few synapses, whereas RGCs cultured in the presence of a feeding layer of astrocytes or astrocyte-conditioned medium show about tenfold more excitatory synapse activity and a fivefold to sevenfold increase in the number of synapse”

“There are several types in the central nervous system (CNS), including astrocytes, oligodendrocytes and microgli”

“In the CNS, cellecell interactions amplify signals [47,68,69].”

“Microglia have been shown to participate in the process of synapse pruning and 344 stripping by selectively contacting synapse with their vicinity, and thus affecting 345 synapse plasticity (51).”

“To this end, an exciting challenge is to decipher adaptive from maladaptive molecular and cellular changes within individual neurons and their supporting cells and the influence they exert on motor circuits after neural trauma (Ilieva et al., 2009; Eroglu and Barres, 2010; Huntley, 2012).”

“Also, the contribution of glial cells, which are in close contact with neuronal components, especially synaptic structures, should be considered in TBI models (Eroglu and Barres, 2010).”

“Astrocytes can release neuroactive substances denominated gliotransmitters that can bind to presynaptic and/or postsynaptic receptors and also can regulate neuronal excitability and synaptic transmission [50-52].”

“of positional cues in the form of morphogenic extracellular signaling molecules 95 (Ullian et al., 2001;Shen and Bargmann, 2003;Colon-Ramos et al., 2007;Ango 96 et al., 2008;Eroglu and Barres, 2010;Tsai et al., 2012;Molofsky et al., 2014).”

“In mammals and Drosophila, synapses are removed actively through engulfment and phagocytosis regulated by glial cells (Eroglu and Barres 2010).”

“Moreover, next-generation interfaces should allow for device removal with minimal damage to tissue or the electrode itself [ 6, 7 ].”

“…state-of-the-art interconnect modules and Ethernet switches integrated with high-bandwidth memory (HBM), the total system power is estimated to be around 1.7 kilowatts for simulating approximately 71% of a brain-scale network (assuming the human brain has around 100 trillion synapses [20, 56]).”

“At 4 days post induction, cells are co-cultured with mouse glia to promote neuronal maturation and synaptic connectivity (Eroglu and Barres 2010; Pfrieger 2009; Pietiläinen et al. 2023).”

“OECs in cluster 4 are distinctive by their expression of several astrocytic markers that regulate synaptogenesis (Thrombospondin 2) and synaptic connectivity, and remove inactive synaptic connections (Complement component 1q family; Christopherson et al., 2005 ; Eroglu and Barres, 2010 ).”

“Glial cells maintain neuronal homeostasis and health by interacting with neurons and regulating synaptic connectivity, 19–22 , 97 and glial dysfunction has arisen as a powerful modulator of AD pathogenesis Although amyloid -β accumulates during the prodromal period of AD, patients do not exhibit…”

“Astrocytes in the CNS play a critical role in neuronal maturation and synaptogenesis [5, 16, 52].”

“Notably, in the human brain, a single protoplasmic astrocyte could contact up to 2 million synapses residing in its territorial domain (107) , forming numerous tripartite synapses (see Section 2) (108) .”

“Astrocytes maintain homeostasis in the brain and modulate synapse formation by mediating neurotransmitter and gliotransmitter release (Eroglu & Barres, 2010; Li et al., 2013; Mazaud et al., 2019) and by responding to signals from neighboring cells (Araque et al., 2002, 2014; Bang et al., 2016;…”

“Glial cells are critical regulators of synaptic connectivity both in healthy and diseased brains [83].”

“For example, reactive astrocytes release molecules activating inflammatory cascades(7) can be neurotoxic and neuroprotective,(8) and can drive synaptogenesis and synaptic pruning.(9,10) Dividing reactive gliosis into subprocesses with potentially opposite effects on epileptogenesis is complicated, but critical to harn…”

“In addition, PSAPs contribute to the maintenance of ion homeostasis, for example by regulating extracellular K concentrations, and pH [22].”

“Astrocytes are critical for synaptogenesis and synaptic maintenance (Ullian et al. 2004; Eroglu and Barres 2010), whereas astroglial plasmalemmal transporters control local concentrations of ions and neurotransmitters, most notably glutamate, which, when not contained, causes local excitotoxicity.”

“The glia and neurons interact in complex ways that are just beginning to be understood (reviewed by Eroglu & Barres, 2010 and Stipursky et al., 2011).”

“Through this mechanism of modulating neuronal excitability, astrocytes are able to influence synaptic plasticity (Araque et al., 1999; Eroglu and Barres, 2010).”

“These cells perform several important homeostatic functions including the maintenance of fluid and neuro-transmitters, induction of synapse formation, and metabolic and neurotrophic support for synapses [110,111].”

“…perform vital roles across the lifespan of a synapse, from synapse formation to synaptic transmission, to synapse elimination (reviewed in Farhy-Tselnicker and Allen, 2018 ; Eroglu and Barres, 2010 ; Shan et al., 2021 ; Verkhratsky and Nedergaard, 2018 ; Lyon and Allen, 2021 ; Nagai et al., 2021 ).”

“Glia not only express ASD-associated genes but also influence neuronal function via non-cell-autonomous mechanisms [ 14–19 ].”

“Incorporating additional biological features — such as receptor subtypes ( Hell, 2016; Kennedy and Ehlers, 2006 ), presynaptic signaling pathways, and glial contributions ( Eroglu and Barres, 2010; Sancho et al., 2021 ) — would broaden its coverage of synaptic and circuit mechanisms.”

“In 2010 the astrocyte results were confirmed and extended by the control of synapse activities: establishment, functions, and plasticity [11].”

“Weighting the Laplacian by conductance captures the actual strength of intercellular connections [25], [26].”

“Proto-plasmic astrocytes in cortex and hippocampus are mainly synaptic maturation, synaptic maintenance and synaptic elimination [118–123].”

“Astrocytes and microglia form the most abundant cell populations in the CNS [6].”

“A human brain contains billions of neurons, linked to one another via hundreds of trillions of tiny contacts called synapses [1, 2] .”

“Astrocytes are glial cells with a variety of homeostatic, synaptic, and neuroprotective functions (Araque et al., 1999; Eroglu & Barres, 2010; Verkhratsky et al., 2019).”

“They contribute to the determination of neuronal cell number and can promote, prune and/or dynamically regulate synaptic connectivity through various mechanisms (vertebrates: Eroglu & Barres, 2010; invertebrates: Corty & Freeman, 2013).”

“Astrocytes are an integral part of the tripartite synapse (Eroglu & Barres, 2010) and play a key role in the regulatory control of synaptic function and plasticity, (Tewari & Parpura, 2016) which in turn play a key role in social behaviour and cognitive functions.”

“Astrocyte heterogeneity in the CNS has recently been described to influence neuronal synaptogenesis and maturation through secretion of several extracellular matrix proteins (Eroglu and Barres, 2010).”

“Regional differences in astrocytes have been recently shown to influence neuronal synaptogenesis and maturation through secretion of several extracellular matrix proteins (Eroglu and Barres, 2010).”

“Synaptic pruning by astrocytes could be promoted by microglia signalling [13].”

“SIMILARITIES BETWEEN HDF AND CNS CELLS Neurons and glia are both affected in psychiatric disorders and both can be considered valid therapeutic targets (Eroglu and Barres, 2010; Sanacora and Banasr, 2013).”

“The functionally diverse glia-neuron interactions rely on a range of both contact-dependent mechanisms as well as soluble factors [146, 147].”

“Research suggested that before and after SCI glia cells regulate many of the signaling mechanisms that control the neural repair ability [1-4].”

“The relevance of astrocytes as active components of synaptic transmission is highlighted by the term ―tripartite synapse‖ (figure 6), which indicates a synaptic structure composed of the astrocyte wrapped around the synapse as well as the presynaptic and postsynaptic terminals [68].”

“Astrocytes aid in the activation of these synapses with targeted release of neurotrophins and d-serine, and thus encourage AMPA receptor expression (Eroglu and Barres, 2010).”

“Weighting the Laplacian by conductance captures the actual strength of intercellular connections [24], [25].”

“Glial cells, which take up more than half of the volume of the human brain (Eroglu and Barres, 2010), used to be thought of as “Nervenkitt” (the German word for nerve glue) (Jäkel and”

“Astrocytic glia are intimately associated with synapses in the neuropil (Allen and Barres, 2005, 2009; Eroglu et al., 2008; Eroglu and Barres, 2010; Halassa and Haydon, 2010; Reichenbach et al., 2010).”

“They regulate blood flow, provide much-needed energy to neurons, and supply the building blocks for neurotransmitters at the synapses, in addition to dynamically contributing to information processing within the central nervous system (Di Castro et al. 2011; Eroglu and Barres 2010; Halassa and Haydon 2010; Haydon and…”

“Regulation of synaptic strength by cytokines The main processes thought to regulate synaptic plasticity are the cell surface delivery and retention of the glutamatergic receptors, NMDA and AMPA (Eroglu & Barres, 2010).”

“Astrocytes appear to be critically important for the formation of synaptic contacts during neural circuit assembly (Eroglu and Barres, 2010).”

“1 Introduction Glia provide neurons with metabolic and structural support as well as play a direct role in guiding neuronal development [83, 271, 303].”

“One important contribution that astrocytes, one glial type, make to neuronal development is promotion of synaptogenesis (Eroglu and Barres, 2010).”