Astrocytic Plasticity Research Articles

АСТРОЦИТАРНАЯ РЕАКЦИЯ ГОЛОВНОГО МОЗГА КРЫС ПРИ ПРОГРЕССИРОВАНИИ ГЛИАЛЬНЫХ ОПУХОЛЕЙ

Background. The study of the heterogeneity and plasticity of astrocytes in the brain, in particular in the peritumoral zone, at different stages of neoplasm growth will help to understand their importance in the progression of glial tumors. Aim. To perform morphometric assessment of astrocytes in the rodent brain during glial tumor progression. Material and methods. Glial brain tumor was modeled in rodents using implantation of glioma C6 cells followed by immunohistochemical assessment of GFAP+-astrocytes in the peritumoral zone in the right hemisphere and a similar zone of the left hemisphere of the rodent brain at different experimental periods. Results. In the early stages of glial tumor growth, there was a statistically significant predominance of cell density and a difference in the morphometric parameters of astrocyte cells in the peritumoral zone of the right hemisphere of the rat brain compared with a similar zone of the left hemisphere. The progression of the glial tumor was accompanied by a significant decrease in the cell density of astrocytes in the peritumoral zone with an increase in reactive changes of astrocytes in a similar zone of the contralateral hemisphere. Conclusions. The development of tumor processes in the brain of rodents is accompanied by activation of astrocytes with the acquisition of a reactive phenotype by cells in the peritumoral zone. At the same time, further progression of the neoplasm suppresses active proliferation of astrocytes.

Central Amygdala Astrocyte Plasticity Underlies GABAergic Dysregulation in Ethanol Dependence.

Dependence is a hallmark of alcohol use disorder characterized by excessive alcohol intake and withdrawal symptoms. The central nucleus of the amygdala (CeA) is a key brain structure underlying the synaptic and behavioral consequences of ethanol dependence. While accumulating evidence suggests that astrocytes regulate synaptic transmission and behavior, there is a limited understanding of the role astrocytes play in ethanol dependence. The present study used a combination of viral labeling, super resolution confocal microscopy, 3D image analysis, and slice electrophysiology to determine the effects of chronic intermittent ethanol (CIE) exposure on astrocyte plasticity in the CeA. During withdrawal from CIE exposure, we observed increased GABA transmission, an upregulation in astrocytic GAT3 levels, and an increased proximity of astrocyte processes near CeA synapses. Furthermore, GAT3 levels and synaptic proximity were positively associated with voluntary ethanol drinking in dependent rats. Slice electrophysiology confirmed that the upregulation in astrocytic GAT3 levels was functional, as CIE exposure unmasked a GAT3-sensitive tonic GABA current in the CeA. A causal role for astrocytic GAT3 in ethanol dependence was assessed using viral-mediated GAT3 overexpression and knockdown approaches. However, GAT3 knockdown or overexpression had no effect on somatic withdrawal symptoms, dependence-escalated ethanol intake, aversion-resistant drinking, or post-dependent ethanol drinking in male or female rats. Moreover, intra-CeA pharmacological inhibition of GAT3 also did not alter dependent ethanol drinking. Together, these findings indicate that ethanol dependence induces GABAergic dysregulation and astrocyte plasticity in the CeA. However, astrocytic GAT3 does not appear necessary for the drinking related phenotypes associated with dependence.

Injury-specific factors in the cerebrospinal fluid regulate astrocyte plasticity in the human brain

The glial environment influences neurological disease progression, yet much of our knowledge still relies on preclinical animal studies, especially regarding astrocyte heterogeneity. In murine models of traumatic brain injury, beneficial functions of proliferating reactive astrocytes on disease outcome have been unraveled, but little is known regarding if and when they are present in human brain pathology. Here we examined a broad spectrum of pathologies with and without intracerebral hemorrhage and found a striking correlation between lesions involving blood–brain barrier rupture and astrocyte proliferation that was further corroborated in an assay probing for neural stem cell potential. Most importantly, proteomic analysis unraveled a crucial signaling pathway regulating this astrocyte plasticity with GALECTIN3 as a novel marker for proliferating astrocytes and the GALECTIN3-binding protein LGALS3BP as a functional hub mediating astrocyte proliferation and neurosphere formation. Taken together, this work identifies a therapeutically relevant astrocyte response and their molecular regulators in different pathologies affecting the human cerebral cortex.

Star power: harnessing the reactive astrocyte response to promote remyelination in multiple sclerosis.

Astrocytes are indispensable for central nervous system development and homeostasis. In response to injury and disease, astrocytes are integral to the immunological- and the, albeit limited, repair response. In this review, we will examine some of the functions reactive astrocytes play in the context of multiple sclerosis and related animal models. We will consider the heterogeneity or plasticity of astrocytes and the mechanisms by which they promote or mitigate demyelination. Finally, we will discuss a set of biomedical strategies that can stimulate astrocytes in their promyelinating response.

The role of astrocyte in the circadian rhythm

The circadian system can be found in nearly all mammalian organs and cells. The maintenance of circadian rhythms is related to the health of human life. Destroying circadian rhythms has a strong correlation with the emergence of many diseases, such as neurological diseases and cardiovascular diseases. Astrocytes are the most common type of cell in the human central nervous system. In recent years, the autonomous regulatory role of astrocytes in the circadian rhythm of the SCN has received increasing attention. This article aims to briefly introduce the role of SCN astrocytes in maintaining circadian rhythm from three aspects: gene expression of astrocytes, regulation of neurotransmitters by astrocytes, and plasticity of astrocytes. At the same time, this article also reviews the relationship between astrocyte activation and circadian rhythm disorders as a neurological disease, and several drugs targeting astrocytes for the treatment of nervous system diseases related to circadian rhythm disorders were proposed to highlight the potential of targeting SCN astrocytes in the treatment of improving circadian rhythm disorders. Finally, this article summarizes current strategies, future challenges, and therapeutic prospects for astrocyte-targeted therapy to improve circadian rhythm disorders. This review aims to highlight SCN astrocytes’ effect on maintaining the circadian rhythm and their related mechanisms and provide a theoretical basis for the future proposal of targeted treatment strategies with astrocytes.

The Masticatory Activity Interference in Quantitative Estimation of CA1, CA3 and Dentate Gyrus Hippocampal Astrocytes of Aged Murine Models and under Environmental Stimulation.

Studies indicating the influence of masticatory dysfunction, due to a soft diet or lack of molars, on impairing spatial memory and learning have led to research about neuronal connections between areas and cell populations possibly affected. In this sense, with scarce detailed data on the subfields of hippocampus in dementia neurodegeneration, there is no information about astrocytic responses in its different layers. Thus, considering this context, the present study evaluated the effects of deprivation and rehabilitation of masticatory activity, aging, and environmental enrichment on the stereological quantification of hippocampal astrocytes from layers CA1, CA3, and DG. For this purpose, we examined mature (6-month-old; 6M), and aged (18-month-old; 18M) mice, subjected to distinct masticatory regimens and environments. Three different regimens of masticatory activity were applied: continuous normal mastication with hard pellets (HD); normal mastication followed by deprived mastication with equal periods of pellets followed by soft powder (HD/SD); or rehabilitated masticatory activity with equal periods of HD, followed by powder, followed by pellets (HD/SD/HD). Under each specific regimen, half of the animals were raised in standard cages (impoverished environment (IE)) and the other half in enriched cages (enriched environment (EE)), mimicking sedentary or active lifestyles. Microscopic stereological, systematic, and random sampling approaches with an optical dissector of GFAP-immunolabeled astrocytes were done, allowing for an astrocyte numerical estimate. Stratum moleculare and hilus, from the dentate gyrus (DG) and Strata Lacunosum-Moleculare, Oriens, and Radiatum, similarly to the dentate gyrus, showed no significant change in any of the investigated variables (age, diet, or environment) in these layers. However, in Stratum radiatum, it was possible to observe significant differences associated with diet regimens and age. Therefore, diet-related differences were found when the HD 18M IE group was compared to the HD/SD/HD 18-month-old group in the same environment (IE) (p = 0.007). In the present study, we present modulatory factors (masticatory function, environmental enrichment, and aging) for the differentiated quantitative laminar response in the hippocampal regions, suggesting other studies to read the plasticity and responsiveness of astrocytes, including the molecular background.

A role of GABAA receptor α1 subunit in the hippocampus for rapid-acting antidepressant-like effects of ketamine

Ketamine can produce rapid-acting antidepressant effects in treatment-resistant patients with depression. Although alterations in glutamatergic and GABAergic neurotransmission in the brain play a role in depression, the precise molecular mechanisms in these neurotransmission underlying ketamine's antidepressant actions remain largely unknown. Mice exposed to FSS (forced swimming stress) showed depression-like behavior and decreased levels of GABA (γ-aminobutyric acid), but not glutamate, in the hippocampus. Ketamine increased GABA levels and decreased glutamate levels in the hippocampus of mice exposed to FSS. There was a correlation between GABA levels and depression-like behavior. Furthermore, ketamine increased the levels of enzymes and transporters on the GABAergic neurons (SAT1, GAD67, GAD65, VGAT and GAT1) and astrocytes (EAAT2 and GAT3), without affecting the levels of enzymes and transporters (SAT2, VGluT1 and GABAAR γ2) on glutamatergic neurons. Moreover, ketamine caused a decreased expression of GABAAR α1 subunit, which was specifically expressed on GABAergic neurons and astrocytes, an increased GABA synthesis and metabolism in GABAergic neurons, a plasticity change in astrocytes, and an increase in ATP (adenosine triphosphate) contents. Finally, GABAAR antagonist bicuculline or ATP exerted a rapid antidepressant-like effect whereas pretreatment with GABAAR agonist muscimol blocked the antidepressant-like effects of ketamine. In addition, pharmacological activation and inhibition of GABAAR modulated the synthesis and metabolism of GABA, and the plasticity of astrocytes in the hippocampus. The present data suggest that ketamine could increase GABA synthesis and astrocyte plasticity through downregulation of GABAAR α1, increases in GABA, and conversion of GABA into ATP, resulting in a rapid-acting antidepressant-like action.This article is part of the Special Issue on ‘Ketamine and its Metabolites’.

Interferon-beta induces major histocompatibility complex of class I (MHC-I) expression and a proinflammatory phenotype in cultivated human astrocytes

Major histocompatibility complex class I (MHC-I) has been implicated in several types of neuroplasticity phenomena. Interferon beta-1b (IFN-β) increases MHC-I expression by motoneurons after sciatic nerve crush in mice, improving axonal growth and functional recovery. Additionally, IFN-β induces glial hypertrophy associated with upregulation of glial fibrillary acidic protein (GFAP) and MHC-I in murine astrocytes in vitro. As knowledge about MHC-I and its role in synaptic plasticity in human astrocytes (HAs) is scarce, we investigated these aspects in mature HAs obtained from the neocortex of patients undergoing surgery due to hippocampal sclerosis. Cells were exposed to media in the absence (0 IU/ml) or presence of IFN-β for 5 days (500 IU/ml). Beta-2 microglobulin (β2m), a component of the MHC-I, GFAP and vimentin proteins, was quantified by flow cytometry (FC) and increased by 100%, 60% and 46%, respectively, after IFN-β exposure. We also performed qRT–PCR gene expression analyses for β2m, GFAP, vimentin, and pro- and anti-inflammatory cytokines. Our data showed that IFN-β-treated astrocytes displayed β2m and GFAP gene upregulation. Additionally, they presented a proinflammatory profile with increase in the IL-6 and IL-1β genes and a tendency to upregulate TNF-α. Moreover, we evaluated the effect of HAs conditioned medium (CM) on the formation/maintenance of neurites/synapses by the PC12 lineage. Synaptophysin protein expression was quantified by FC. The CM of IFN-β-activated astrocytes was not harmful to PC12 neurites, and there was no change in synaptophysin protein expression. Therefore, IFN-β activated HAs by increasing GFAP, vimentin and MHC-I protein expression. Like MHC-I modulation and astrocyte activation may be protective after peripheral nerve damage and in some neurodegenerative conditions, this study opens perspectives on the pathophysiological roles of astroglial MHC-I in the human CNS.

IN BRAIN POST-ISCHEMIC PLASTICITY, Na+/Ca2+ EXCHANGER 1 AND Ascl1 INTERVENE IN MICROGLIA-DEPENDENT CONVERSION OF ASTROCYTES INTO NEURONAL LINEAGE

The intricate glia interaction occurring after stroke strongly depend on the maintenance of intraglial ionic homeostasis. Among the several ionic channels and transporters, the plasmamembrane Na+/Ca2+ exchanger (NCX) represents a key player in maintaining astroglial Na+ and Ca2+ homeostasis.Here, using a combined in vitro, in vivo and ex vivo experimental strategy we evaluated whether microglia responding to ischemic injury may influence the morphological and the transcriptional plasticity of post-ischemic astrocytes. Astrocyte plasticity was monitored by the expression of the transcription factor Acheate-scute like 1 (Ascl1), which plays a central role in the commitment of astrocytes towards the neuronal lineage. Furthermore, we explored the implication of NCX1 expression and activity in mediating Ascl1-dependent post-ischemic astrocyte remodeling.We demonstrated that: (a) in astrocytes co-cultured with microglia the exposure to oxygen and glucose deprivation followed by 7 days of reoxygenation induced a prevalence of bipolar astrocytes overexpressing Ascl1 and NCX1, whereas this did not occur in monocultured astrocytes; (b) the reoxygenation of anoxic astrocytes with the conditioned medium derived from IL-4 stimulated microglia strongly elicited the astrocytic co-expression of Ascl1 and NCX1; (c) Ascl1 expression in anoxic astrocytes was dependenton NCX1 since its silencing prevented Ascl1 expression both in in vitro and in post-ischemic ex vivo experimental conditions.Collectively, the results of our study support the idea that, after brain ischemia, astrocyte-microglia crosstalk can influence astrocytic morphology and its Ascl1 expression. This phenomenon is strictly dependent on ischemia-induced increase of NCX1 which in turn induces Ascl1 overexpression possibly through astrocytic Ca2+ elevation.

Treadmill exercise promotes retinal astrocyte plasticity and protects against retinal degeneration in a mouse model of light-induced retinal degeneration.

Exercise is an effective neuroprotective intervention that preserves retinal function and structure in several animal models of retinal degeneration. However, the retinal cell types governing exercise-induced neuroprotection remain elusive. Previously, we found exercise-induced retinal neuroprotection was associated with increased levels of retinal brain-derived neurotrophic factor (BDNF) and required intact signal transduction with its high-affinity receptor, tropomyosin kinase B (TrkB). Brain studies have shown astrocytes express BDNF and TrkB and that decreased BDNF-TrkB signaling in astrocytes contributes to neurodegeneration. Additionally, exercise has been shown to alter astrocyte morphology. Using a light-induced retinal degeneration (LIRD) model, we investigated how exercise influences retinal astrocytes in adult male BALB/c mice. Treadmill exercise in dim control and LIRD groups had increased astrocyte density, GFAP labeling, branching, dendritic endpoints, and arborization. Meanwhile, inactive LIRD animals had significant reductions in all measured parameters. Additionally, exercised groups had increased astrocytic BDNF expression that was visualized using proximity ligase assay. Isolated retinal astrocytes from exercised LIRD groups had significantly increased expression of a specific isoform of TrkB associated with cell survival, TrkB.FL. Conversely, inactive LIRD isolated retinal astrocytes had significantly increased expression of TrkB.T1, which has been implicated in neuronal cell death. Our data indicate exercise not only alters retinal astrocyte morphology but also promotes specific BDNF-TrkB signaling associated with cell survival and protection during retinal degeneration. These findings provide novel insights into the effects of treadmill exercise on retinal astrocyte morphology and cellular expression, highlighting retinal astrocytes as a potential cell type involved in BDNF-TrkB signaling.

The role of astrocyte structural plasticity in regulating neural circuit function and behavior.

Brain circuits undergo substantial structural changes during development, driven by the formation, stabilization, and elimination of synapses. Synaptic connections continue to undergo experience‐dependent structural rearrangements throughout life, which are postulated to underlie learning and memory. Astrocytes, a major glial cell type in the brain, are physically in contact with synaptic circuits through their structural ensheathment of synapses. Astrocytes strongly contribute to the remodeling of synaptic structures in healthy and diseased central nervous systems by regulating synaptic connectivity and behaviors. However, whether structural plasticity of astrocytes is involved in their critical functions at the synapse is unknown. This review will discuss the emerging evidence linking astrocytic structural plasticity to synaptic circuit remodeling and regulation of behaviors. Moreover, we will survey possible molecular and cellular mechanisms regulating the structural plasticity of astrocytes and their non‐cell‐autonomous effects on neuronal plasticity. Finally, we will discuss how astrocyte morphological changes in different physiological states and disease conditions contribute to neuronal circuit function and dysfunction.

Astroglia in the Vulnerability to and Maintenance of Stress-Mediated Neuropathology and Depression.

Significant stress exposure and psychiatric depression are associated with morphological, biochemical, and physiological disturbances of astrocytes in specific brain regions relevant to the pathophysiology of those disorders, suggesting that astrocytes are involved in the mechanisms underlying the vulnerability to or maintenance of stress-related neuropathology and depression. To understand those mechanisms a variety of studies have probed the effect of various modalities of stress exposure on the metabolism, gene expression and plasticity of astrocytes. These studies have uncovered the participation of various cellular pathways, such as those for intracellular calcium regulation, neuroimmune responses, extracellular ionic regulation, gap junctions-based cellular communication, and regulation of neurotransmitter and gliotransmitter release and uptake. More recently epigenetic modifications resulting from exposure to chronic forms of stress or to early life adversity have been suggested to affect not only neuronal mechanisms but also gene expression and physiology of astrocytes and other glial cells. However, much remains to be learned to understand the specific role of those and other modifications in the astroglial contribution to the vulnerability to and maintenance of stress-related disorders and depression, and for leveraging that knowledge to achieve more effective psychiatric therapies.

SOX2 modulated astrocytic process plasticity is involved in arsenic-induced metabolic disorders

Metabolic disorders induced by arsenic exposure have attracted great public concern. However, it remains unclear whether hypothalamus-based central regulation mechanisms are involved in this process. Here, we exposed mice to 100 μg/L arsenic in drinking water and established a chronic arsenic exposure model. Our study revealed that chronic arsenic exposure caused metabolic disorders in mice including impaired glucose metabolism and decreased energy expenditure. Arsenic exposure also impaired glucose sensing and the activation of proopiomelanocortin (POMC) neurons in the hypothalamus. In particular, arsenic exposure damaged the plasticity of hypothalamic astrocytic process. Further research revealed that arsenic exposure inhibited the expression of sex-determining region Y-Box 2 (SOX2), which decreased the expression level of insulin receptors (INSRs) and the phosphorylation of AKT. The conditional deletion of astrocytic SOX2 exacerbated arsenic-induced effects on metabolic disorders, the impairment of hypothalamic astrocytic processes, and the inhibition of INSR/AKT signaling. Furthermore, the arsenic-induced impairment of astrocytic processes and inhibitory effects on INSR/AKT signaling were reversed by SOX2 overexpression in primary hypothalamic astrocytes. Together, we demonstrated here that chronic arsenic exposure caused metabolic disorders by impairing SOX2-modulated hypothalamic astrocytic process plasticity in mice. Our study provides evidence of novel central regulatory mechanisms underlying arsenic-induced metabolic disorders and emphasizes the crucial role of SOX2 in regulating the process plasticity of adult astrocytes.

Dihydromyricetin improves social isolation-induced cognitive impairments and astrocytic changes in mice

Social isolation induces stress, anxiety, and mild cognitive impairment that could progress towards irreversible brain damage. A probable player in the mechanism of social isolation-induced anxiety is astrocytes, specialized glial cells that support proper brain function. Using a social isolation mouse model, we observed worsened cognitive and memory abilities with reductions of Object Recognition Index (ORI) in novel object recognition test and Recognition Index (RI) in novel context recognition test. Social isolation also increased astrocyte density, reduced astrocyte size with shorter branches, and reduced morphological complexity in the hippocampus. Dihydromyricetin, a flavonoid that we previously demonstrated to have anxiolytic properties, improved memory/cognition and restored astrocyte plasticity in these mice. Our study indicates astrocytic involvement in social isolation-induced cognitive impairment as well as anxiety and suggest dihydromyricetin as an early-stage intervention against anxiety, cognitive impairment, and potential permanent brain damage.

Astrocyte plasticity in mice ensures continued endfoot coverage of cerebral blood vessels following injury and declines with age

Astrocytes extend endfeet that enwrap the vasculature, and disruptions to this association which may occur in disease coincide with breaches in blood-brain barrier (BBB) integrity. Here we investigate if focal ablation of astrocytes is sufficient to disrupt the BBB in mice. Targeted two-photon chemical apoptotic ablation of astrocytes induced a plasticity response whereby surrounding astrocytes extended processes to cover vascular vacancies. In young animals, replacement processes occur in advance of endfoot retraction, but this is delayed in aged animals. Stimulation of replacement astrocytes results in constriction of pre-capillary arterioles, suggesting that replacement astrocytes are functional. Pharmacological inhibition of pSTAT3, as well as astrocyte specific deletion of pSTAT3, reduces astrocyte replacement post-ablation, without perturbations to BBB integrity. Similar endfoot replacement occurs following astrocyte cell death due to reperfusion in a stroke model. Together, these studies uncover the ability of astrocytes to maintain cerebrovascular coverage via substitution from nearby cells.

Metabolic Plasticity of Astrocytes

Metabolic Plasticity of Astrocytes

Time-dependent changes in hippocampal and striatal glycogen long after maze training in male rats

Long-lasting biological changes reflecting past experience have been studied in and typically attributed to neurons in the brain. Astrocytes, which are also present in large number in the brain, have recently been found to contribute critically to learning and memory processing. In the brain, glycogen is primarily found in astrocytes and is metabolized to lactate, which can be released from astrocytes. Here we report that astrocytes themselves have intrinsic neurochemical plasticity that alters the availability and provision of metabolic substrates long after an experience. Rats were trained to find food on one of two versions of a 4-arm maze: a hippocampus-sensitive place task and a striatum-sensitive response task. Remarkably, hippocampal glycogen content increased while striatal levels decreased during the 30 days after rats were trained to find food in the place version, but not the response version, of the maze tasks. A long-term consequence of the durable changes in glycogen stores was seen in task-by-site differences in extracellular lactate responses activated by testing on a working memory task administered 30 days after initial training, the time when differences in glycogen content were most robust. These results suggest that astrocytic plasticity initiated by a single experience may augment future availability of energy reserves, perhaps priming brain areas to process learning of subsequent experiences more effectively.

Administration of cyclic glycine-proline during infancy improves adult spatial memory, astrocyte plasticity, vascularization and GluR-1 expression in rats

ABSTRACT Cyclic glycine-proline (cGP) is a natural nutrient of breast milk and plays a role in regulating the function of insulin-like growth factor-1 (IGF-1). IGF-1 function is essential for post-natal brain development and adult cognitive function. We evaluated the effects of cGP on spatial memory and histological changes in the hippocampus of the adult rats following infancy administration. Infant rats were treated with either cGP or saline between post-natal days 8 and 22 via oral administration to lactating dams. The spatial memory was evaluated between post-natal days 70 and 75 using Morris water maze tests. The changes of capillaries, astrocytes, synaptophysin and glutamate receptor-1 were examined in the CA1 stratum radiatum of the hippocampus. Compared to saline-treated group, cGP-treated group showed higher path efficiency of entry and lower average heading errors to the platform zone. cGP-treated group also showed longer, larger and more astrocytic processes, more capillaries and higher glutamate receptor-1 expression. The rats made less average heading error to the platform zone have more capillaries, larger and longer astrocytic branches. Thus cGP treatment/supplementation during infancy moderately improved adulthood spatial memory. This long-lasting effect of cGP on memory could be mediated via promoting astrocytic plasticity, vascularization and glutamate trafficking. Therefore, cGP may have a role in regulating IGF-1 function during brain development.

Astrocyte arborization enhances Ca2+ but not cAMP signaling plasticity

The plasticity of astrocytes is fundamental for their principal function, maintaining homeostasis of the central nervous system throughout life, and is associated with diverse exposomal challenges. Here, we used cultured astrocytes to investigate at subcellular level basic cell processes under controlled environmental conditions. We compared astroglial functional and signaling plasticity in standard serum‐containing growth medium, a condition mimicking pathologic conditions, and in medium without serum, favoring the acquisition of arborized morphology. Using opto−/electrophysiologic techniques, we examined cell viability, expression of astroglial markers, vesicle dynamics, and cytosolic Ca2+ and cAMP signaling. The results revealed altered vesicle dynamics in arborized astrocytes that was associated with increased resting [Ca2+]i and increased subcellular heterogeneity in [Ca2+]i, whereas [cAMP]i subcellular dynamics remained stable in both cultures, indicating that cAMP signaling is less prone to plastic remodeling than Ca2+ signaling, possibly also in in vivo contexts.

Homeostatic Regulation of Astrocytes by Visual Experience in the Developing Primary Visual Cortex.

During postnatal development, sensory experience shapes the organization and function of cortical circuits. Previous studies focusing on experience-dependent plasticity of neurons have revealed a variety of mechanisms underlying cortical circuit rewiring. Emerging evidence shows that astrocytes play important roles in shaping cortical circuits through extensive interactions with different types of neurons and other glia cells. However, it remains unclear how astrocytes respond to sensory experience during postnatal development. In the present study, we profiled the maturation of astrocytes in the primary visual cortex (V1) at different postnatal stages. We then investigated the anatomical and physiological changes of astrocytes in V1 induced by multiple types of visual experience within 4 postnatal weeks. Compared with monocular deprivation during the critical period, binocular deprivation showed stronger impact on reactive astrocytes in V1. Moreover, long-term binocular deprivation significantly reduced the density of reactive astrocytes in layer 2/3 of V1 while strengthening gap junction couplings between astrocytes at the same time. Therefore, our data demonstrated that cortical astrocytes could undergo homeostatic plasticity in response to long-term changes of sensory inputs. The plasticity of astrocytes may interact with the plasticity of neurons to cooperatively shape cortical circuit refinement during postnatal development.