Inhibitory input directs astrocyte morphogenesis through glial GABABR.

Communication between neurons and glia has an important role in establishing and maintaining higher-order brain function1. Astrocytes are endowed with complex morphologies, placing their peripheral processes in close proximity to neuronal synapses and directly contributing to their regulation of brain circuits2-4. Recent studies have shown that excitatory neuronal activity promotes oligodendrocyte differentiation5-7; whether inhibitory neurotransmission regulates astrocyte morphogenesis during development is unclear. Here we show that inhibitory neuron activity is necessary and sufficient for astrocyte morphogenesis. We found that input from inhibitory neurons functions through astrocytic GABAB receptor (GABABR) and that its deletion in astrocytes results in a loss of morphological complexity across a host of brain regions and disruption of circuit function. Expression of GABABR in developing astrocytes is regulated in a region-specific manner by SOX9 or NFIA and deletion of these transcription factors results in region-specific defects in astrocyte morphogenesis, which is conferred by interactions with transcription factors exhibiting region-restricted patterns of expression. Together, our studies identify input from inhibitory neurons and astrocytic GABABR as universal regulators of morphogenesis, while further revealing a combinatorial code of region-specific transcriptional dependencies for astrocyte development that is intertwined with activity-dependent processes.

Remote neuronal activity drives glioma progression through SEMA4F.

The tumour microenvironment plays an essential role in malignancy, and neurons have emerged as a key component of the tumour microenvironment that promotes tumourigenesis across a host of cancers1,2. Recent studies on glioblastoma (GBM) highlight bidirectional signalling between tumours and neurons that propagates a vicious cycle of proliferation, synaptic integration and brain hyperactivity3-8; however, the identity of neuronal subtypes and tumour subpopulations driving this phenomenon is incompletely understood. Here we show that callosal projection neurons located in the hemisphere contralateral to primary GBM tumours promote progression and widespread infiltration. Using this platform to examine GBM infiltration, we identified an activity-dependent infiltrating population present at the leading edge of mouse and human tumours that is enriched for axon guidance genes. High-throughput, in vivo screening of these genes identified SEMA4F as a key regulator of tumourigenesis and activity-dependent progression. Furthermore, SEMA4F promotes the activity-dependent infiltrating population and propagates bidirectional signalling with neurons by remodelling tumour-adjacent synapses towards brain network hyperactivity. Collectively our studies demonstrate that subsets of neurons in locations remote to primary GBM promote malignant progression, and also show new mechanisms of glioma progression that are regulated by neuronal activity.

PIK3CA variants selectively initiate brain hyperactivity during gliomagenesis.

Glioblastoma is a universally lethal form of brain cancer that exhibits an array of pathophysiological phenotypes, many of which are mediated by interactions with the neuronal microenvironment1,2. Recent studies have shown that increases in neuronal activity have an important role in the proliferation and progression of glioblastoma3,4. Whether there is reciprocal crosstalk between glioblastoma and neurons remains poorly defined, as the mechanisms that underlie how these tumours remodel the neuronal milieu towards increased activity are unknown. Here, using a native mouse model of glioblastoma, we develop a high-throughput in vivo screening platform and discover several driver variants of PIK3CA. We show that tumours driven by these variants have divergent molecular properties that manifest in selective initiation of brain hyperexcitability and remodelling of the synaptic constituency. Furthermore, secreted members of the glypican (GPC) family are selectively expressed in these tumours, and GPC3 drives gliomagenesis and hyperexcitability. Together, our studies illustrate the importance of functionally interrogating diverse tumour phenotypes driven by individual, yet related, variants and reveal how glioblastoma alters the neuronal microenvironment.

Pudilan Keyanning mouthwash inhibits dextran-dependent aggregation and biofilm organization of Streptococcus mutans.

AIMS: This research aimed to investigate the inhibitory effects of Pudilan mouthwash (PDL) on Streptococcus mutans (S. mutans) biofilms and identify its chemical components. METHODS AND RESULTS: The impacts of 100% concentrated PDL on S. mutans biofilm were detected by colony-forming unit (CFU) assays, crystal violet staining, confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), and quantitative real-time PCR (qRT‒PCR). The biocompatibility with human gingival fibroblasts (HGFs) was evaluated by Cell-Counting-Kit-8 (CCK-8) assay. And chemical components were identified by UPLC-HRMS. PBS and 0.12% chlorhexidine were used as negative and positive controls, respectively. Results indicate early 8-h S. mutans biofilms are sensitive to PDL. Additionally, it leads to a decrease in bacterial activities and dextran-dependent aggregation in 24-h S. mutans biofilms. PDL significantly downregulates the gene expression of gtfB/C/D and smc. And 114 components are identified. CONCLUSIONS: PDL has an inhibitory effect on S. mutans and favorable biocompatibility. It has potential to be exploited as a novel anti-biofilm agent.

New measure of functional tooth loss for successful Oral ageing: a cross-sectional study.

BACKGROUND: This cross-sectional study evaluated the impacts of functional tooth loss on oral health-related quality of life (OHRQoL) among elderly people compared with the impacts of several common indicators of oral health. Additionally, the cut-off of functional tooth loss needed for a better OHRQoL was investigated to establish a new measure for successful oral ageing. METHODS: Data from people aged 65-74 were extracted from the Fourth National Oral Health Survey in Sichuan, China. Functional tooth loss was defined as both natural tooth loss and nonfunctional teeth, such as third molars, residual roots, and removable dentures. The cut-offs of tooth loss were first identified as 12, based on the previous definition of functional dentition (≥20 natural teeth except the third molars), and 14, 16, or 18 for further investigation. OHRQoL was evaluated by the standardized Geriatric Oral Health Assessment Index (sGOHAI) score. Logistic regression was performed to estimate the impacts on OHRQoL. Additionally, subgroup analyses were conducted using the stratified chi-square test to explore the effect of functional tooth loss at each position. RESULTS: The mean GOHAI score of the 744 participants was 48.25 ± 7.62. Elderly people who had lost ≤12 functional teeth had greater odds of reporting a higher sGOHAI score than those who had lost more functional teeth (odds ratio (OR) 1.49, 95% confidence interval (CI) 1.05-2.11). No significant difference in the sGOHAI score was detected between people who had lost 13-16 functional teeth and those who had lost ≤12 functional teeth (0.61, 0.35-1.07). The loss of second premolars and first and second molars had great impacts on the sGOHAI score when ≤12 or ≤ 16 functional teeth had been lost. CONCLUSIONS: Compared with natural tooth loss, functional dentition and occluding pairs, functional tooth loss can be a better indicator of OHRQoL in the elderly population. Sixteen remaining functional teeth seem to be sufficient to maintain good OHRQoL and successful oral ageing despite that number being previously acknowledged as ≥20 teeth.

Loss of Oxidation Resistance 1, OXR1, Is Associated with an Autosomal-Recessive Neurological Disease with Cerebellar Atrophy and Lysosomal Dysfunction.

We report an early-onset autosomal-recessive neurological disease with cerebellar atrophy and lysosomal dysfunction. We identified bi-allelic loss-of-function (LoF) variants in Oxidative Resistance 1 (OXR1) in five individuals from three families; these individuals presented with a history of severe global developmental delay, current intellectual disability, language delay, cerebellar atrophy, and seizures. While OXR1 is known to play a role in oxidative stress resistance, its molecular functions are not well established. OXR1 contains three conserved domains: LysM, GRAM, and TLDc. The gene encodes at least six transcripts, including some that only consist of the C-terminal TLDc domain. We utilized Drosophila to assess the phenotypes associated with loss of mustard (mtd), the fly homolog of OXR1. Strong LoF mutants exhibit late pupal lethality or pupal eclosion defects. Interestingly, although mtd encodes 26 transcripts, severe LoF and null mutations can be rescued by a single short human OXR1 cDNA that only contains the TLDc domain. Similar rescue is observed with the TLDc domain of NCOA7, another human homolog of mtd. Loss of mtd in neurons leads to massive cell loss, early death, and an accumulation of aberrant lysosomal structures, similar to what we observe in fibroblasts of affected individuals. Our data indicate that mtd and OXR1 are required for proper lysosomal function; this is consistent with observations that NCOA7 is required for lysosomal acidification.

Measuring Roadway Lane Widths Using Connected Vehicle Sensor Data.

The United States has over three trillion vehicle miles of travel annually on over four million miles of public roadways, which require regular maintenance. To maintain and improve these facilities, agencies often temporarily close lanes, reconfigure lane geometry, or completely close the road depending on the scope of the construction project. Lane widths of less than 11 feet in construction zones can impact highway capacity and crash rates. Crash data can be used to identify locations where the road geometry could be improved. However, this is a manual process that does not scale well. This paper describes findings for using data from onboard sensors in production vehicles for measuring lane widths. Over 200 miles of roadway on US-52, US-41, and I-65 in Indiana were measured using vehicle sensor data and compared with mobile LiDAR point clouds as ground truth and had a root mean square error of approximately 0.24 feet. The novelty of these results is that vehicle sensors can identify when work zones use lane widths substantially narrower than the 11 foot standard at a network level and can be used to aid in the inspection and verification of construction specification conformity. This information would contribute to the construction inspection performed by agencies in a safer, more efficient way.

[Recent Developments and Future Directions of Oral Healthcare System and Dental Public Health System in China in Light of the Current Global Emergency].

The study is aimed to help promote the development of the oral healthcare system and dental public health system in China and to help achieve the goal of improving the nation's oral health. We herein provided an overview and critical evaluation of recent developments in oral healthcare systems and dental public health systems in China and other countries, and discussed a number of potential directions for the future development of dental public health. The current global public health emergency of the coronavirus disease 2019 (COVID-19) pandemic was also taken into account in our discussions. Thus, to facilitate the accomplishment of the goals of the Healthy China 2030 Program, we suggested the establishment of a community-based, prevention-oriented model for the oral healthcare system and dental public health system. The model we proposed features the integration of oral and general health services, the utilization of technological innovations and big data concerning health, and a forceful promotion of remote dental services focused on prevention and early diagnosis and treatment. Furthermore, under the background of COVID-19 becoming a normal part of people's lives, we should adopt differentiated prevention and protection measures and emergency response preplans appropriate for the actual epidemic situation of a particular region so that clinical services are strengthened while unnecessary wastes of resources are avoided. We should actively explore for alternative approaches to care in the face of special circumstances.

Non-affinity adsorption of nanorods onto smooth walls via an entropy driven mechanism.

Preferential adsorption of nanorods onto smooth walls is investigated using dissipative particle dynamics in the absence of specific attraction and a depletant. Although the translational and rotational entropy of nanorods is significantly reduced after adsorption, the effective attraction between the nanorod and wall is clearly identified based on the distribution profile of rods. As the rod length increases, the attractive interaction grows stronger and clusters of aligned nanorods can emerge on the smooth wall. However, the presence of a depletion zone of nanorods adjacent to the adsorbed layer gives zero surface excess. These two regions correspond to the primary minimum and maximum mean force potentials observed. Since adsorbed nanorods lose their rotational and translational entropy, the strong adsorption of long nanorods has to be attributed to the entropy gain associated with the increase in free volume for the solvent in this athermal system. Nonetheless, as the surface roughness is present, entropy-driven attraction is lessened, similar to the depletion force between colloids.

Processing Strategy and Comparative Performance of Different Mobile LiDAR System Grades for Bridge Monitoring: A Case Study.

Collecting precise as-built data is essential for tracking construction progress. Three-dimensional models generated from such data capture the as-is conditions of the structures, providing valuable information for monitoring existing infrastructure over time. As-built data can be acquired using a wide range of remote sensing technologies, among which mobile LiDAR is gaining increasing attention due to its ability to collect high-resolution data over a relatively large area in a short time. The quality of mobile LiDAR data depends not only on the grade of onboard LiDAR scanners but also on the accuracy of direct georeferencing information and system calibration. Consequently, millimeter-level accuracy is difficult to achieve. In this study, the performance of mapping-grade and surveying-grade mobile LiDAR systems for bridge monitoring is evaluated against static laser scanners. Field surveys were conducted over a concrete bridge where grinding was required to achieve desired smoothness. A semi-automated, feature-based fine registration strategy is proposed to compensate for the impact of georeferencing and system calibration errors on mobile LiDAR data. Bridge deck thickness is evaluated using surface segments to minimize the impact of inherent noise in the point cloud. The results show that the two grades of mobile LiDAR delivered thickness estimates that are in agreement with those derived from static laser scanning in the 1 cm range. The mobile LiDAR data acquisition took roughly five minutes without having a significant impact on traffic, while the static laser scanning required more than three hours.

Hepatocellular carcinoma-associated single-nucleotide variants and deletions identified by the use of genome-wide high-throughput analysis of hepatitis B virus.

This study investigated hepatitis B virus (HBV) single-nucleotide variants (SNVs) and deletion mutations linked with hepatocellular carcinoma (HCC). Ninety-three HCC patients and 108 non-HCC patients were enrolled for HBV genome-wide next-generation sequencing (NGS) analysis. A systematic literature review and a meta-analysis were performed to validate NGS-defined HCC-associated SNVs and deletions. The experimental results identified 60 NGS-defined HCC-associated SNVs, including 41 novel SNVs, and their pathogenic frequencies. Each SNV was specific for either genotype B (n = 24) or genotype C (n = 34), except for nt53C, which was present in both genotypes. The pathogenic frequencies of these HCC-associated SNVs showed a distinct U-shaped distribution pattern. According to the meta-analysis and literature review, 167 HBV variants from 109 publications were categorized into four levels (A-D) of supporting evidence that they are associated with HCC. The proportion of NGS-defined HCC-associated SNVs among these HBV variants declined significantly from 75% of 12 HCC-associated variants by meta-analysis (Level A) to 0% of 10 HCC-unassociated variants by meta-analysis (Level D) (P < 0.0001). PreS deletions were significantly associated with HCC, in terms of deletion index, for both genotypes B (P = 0.030) and C (P = 0.049). For genotype C, preS deletions involving a specific fragment (nt2977-3013) were significantly associated with HCC (HCC versus non-HCC, 6/34 versus 0/32, P = 0.025). Meta-analysis of preS deletions showed significant association with HCC (summary odds ratio 3.0; 95% confidence interval 2.3-3.9). Transfection of Huh7 cells showed that all of the five novel NGS-defined HCC-associated SNVs in the small surface region influenced hepatocarcinogenesis pathways, including endoplasmic reticulum-stress and DNA repair systems, as shown by microarray, real-time polymerase chain reaction and western blot analysis. Their carcinogenic mechanisms are worthy of further research. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

BLMP-1/Blimp-1 regulates the spatiotemporal cell migration pattern in C. elegans.

Spatiotemporal regulation of cell migration is crucial for animal development and organogenesis. Compared to spatial signals, little is known about temporal signals and the mechanisms integrating the two. In the Caenorhabditis elegans hermaphrodite, the stereotyped migration pattern of two somatic distal tip cells (DTCs) is responsible for shaping the gonad. Guidance receptor UNC-5 is necessary for the dorsalward migration of DTCs. We found that BLMP-1, similar to the mammalian zinc finger transcription repressor Blimp-1/PRDI-BF1, prevents precocious dorsalward turning by inhibiting precocious unc-5 transcription and is only expressed in DTCs before they make the dorsalward turn. Constitutive expression of blmp-1 when BLMP-1 would normally disappear delays unc-5 transcription and causes turn retardation, demonstrating the functional significance of blmp-1 down-regulation. Correct timing of BLMP-1 down-regulation is redundantly regulated by heterochronic genes daf-12, lin-29, and dre-1, which regulate the temporal fates of various tissues. DAF-12, a steroid hormone receptor, and LIN-29, a zinc finger transcription factor, repress blmp-1 transcription, while DRE-1, the F-Box protein of an SCF ubiquitin ligase complex, binds to BLMP-1 and promotes its degradation. We have therefore identified a gene circuit that integrates the temporal and spatial signals and coordinates with overall development of the organism to direct cell migration during organogenesis. The tumor suppressor gene product FBXO11 (human DRE-1 ortholog) also binds to PRDI-BF1 in human cell cultures. Our data suggest evolutionary conservation of these interactions and underscore the importance of DRE-1/FBXO11-mediated BLMP-1/PRDI-BF1 degradation in cellular state transitions during metazoan development.

Distribution and ecological risk assessment of antibiotics in different freshwater aquaculture ponds in a typical agricultural plain, China.

Freshwater aquaculture serves as a significant focal point for antibiotic contamination, yet understanding antibiotic distribution across different aquaculture models and stages remains limited. This study evaluated antibiotic pollution in three distinct freshwater aquaculture models: rice-crayfish coculture, fish aquaculture, and crab-crayfish aquaculture, during various aquaculture stages. Of the 33 target antibiotics, 16 antibiotics were detected, with the total concentrations ranging from 111.81 ng/L to 15,949.05 ng/L in water and 10.11 ng/g to 8986.30 ng/g in sediment. Among these antibiotics, erythromycin and lomefloxacin are prohibited for use in Chinese aquaculture. Dominant antibiotics in water included lincomycin, enrofloxacin, and enoxacin, whereas in sediment, oxytetracycline and erythromycin were predominant. Notably, lincomycin emerged as a dominant antibiotic in aquaculture for the first time. The concentrations of these dominant antibiotics were high compared to other aquaculture settings and exhibited elevated ecological risk. Critical periods for antibiotic contamination in water and sediment were found to be incongruent, occurring during the rainy season in July for water and the dry season in October for sediment. Notably, the rice-crayfish coculture model exerts a good effect in reducing antibiotic pollution. Overall, these findings offer valuable evidence for the healthful and sustainable advancement of aquaculture.

Morphology and Composition of Lumbar Intervertebral Discs: Comparative Analyses of Manual Measurement and Computer-Assisted Algorithms.

BACKGROUND: The morphology and internal composition, particularly the nucleus-to-cross sectional area (NP-to-CSA) ratio of the lumbar intervertebral discs (IVDs), is important information for finite element models (FEMs) of spinal loadings and biomechanical behaviors, and, yet, this has not been well investigated and reported. METHODS: Anonymized MRI scans were retrieved from a previously established database, including a total of 400 lumbar IVDs from 123 subjects (58 F and 65 M). Measurements were conducted manually by a spine surgeon and using two computer-assisted segmentation algorithms, i.e., fuzzy C-means (FCM) and region growing (RG). The respective results were compared. The influence of gender and spinal level was also investigated. RESULTS: Ratios derived from manual measurements and the two computer-assisted algorithms (FCM and RG) were 46%, 39%, and 38%, respectively. Ratios derived manually were significantly larger. CONCLUSIONS: Computer-assisted methods provide reliable outcomes that are traditionally difficult for the manual measurement of internal composition. FEMs should consider the variability of NP-to-CSA ratios when studying the biomechanical behavior of the spine.

Sculpting Astrocyte Diversity through Circuits and Transcription.

Astrocytes are the most abundant glial cell in the central nervous system and occupy a wide range of roles that are essential for brain function. Over the past few years, evidence has emerged that astrocytes exhibit cellular and molecular heterogeneity, raising the possibility that subsets of astrocytes are functionally distinct and that transcriptional mechanisms are involved in encoding this prospective diversity. In this review, we focus on three emerging areas of astrocyte biology: region-specific circuit regulation, molecular diversity, and transcriptional regulation. This review highlights our nascent understanding of how molecular diversity is converted to functional diversity of astrocytes through the lens of brain region-specific circuits. We articulate our understanding of how transcriptional mechanisms regulate this diversity and key areas that need further exploration to achieve the overarching goal of a functional taxonomy of astrocytes in the brain.

ADPL: Adaptive Dual Path Learning for Domain Adaptation of Semantic Segmentation.

To alleviate the need for large-scale pixel-wise annotations, domain adaptation for semantic segmentation trains segmentation models on synthetic data (source) with computer-generated annotations, which can be then generalized to segment realistic images (target). Recently, self-supervised learning (SSL) with a combination of image-to-image translation shows great effectiveness in adaptive segmentation. The most common practice is to perform SSL along with image translation to well align a single domain (source or target). However, in this single-domain paradigm, unavoidable visual inconsistency raised by image translation may affect subsequent learning. In addition, pseudo labels generated by a single segmentation model aligned in either the source or target domain may be not accurate enough for SSL. In this paper, based on the observation that domain adaptation frameworks performed in the source and target domain are almost complementary, we propose a novel adaptive dual path learning (ADPL) framework to alleviate visual inconsistency and promote pseudo-labeling by introducing two interactive single-domain adaptation paths aligned in source and target domain respectively. To fully explore the potential of this dual-path design, novel technologies such as dual path image translation (DPIT), dual path adaptive segmentation (DPAS), dual path pseudo label generation (DPPLG) and Adaptive ClassMix are proposed. The inference of ADPL is extremely simple, only one segmentation model in the target domain is employed. Our ADPL outperforms the state-of-the-art methods by large margins on GTA5 →Cityscapes, SYNTHIA → Cityscapes and GTA5 →BDD100K scenarios. Code and models are available at https://github.com/royee182/DPL.

Social deprivation induces astrocytic TRPA1-GABA suppression of hippocampal circuits.

Social experience is essential for the development and maintenance of higher-order brain function. Social deprivation results in a host of cognitive deficits, and cellular studies have largely focused on associated neuronal dysregulation; how astrocyte function is impacted by social deprivation is unknown. Here, we show that hippocampal astrocytes from juvenile mice subjected to social isolation exhibit increased Ca2+ activity and global changes in gene expression. We found that the Ca2+ channel TRPA1 is upregulated in astrocytes after social deprivation and astrocyte-specific deletion of TRPA1 reverses the physiological and cognitive deficits associated with social deprivation. Mechanistically, TRPA1 inhibition of hippocampal circuits is mediated by a parallel increase of astrocytic production and release of the inhibitory neurotransmitter GABA after social deprivation. Collectively, our studies reveal how astrocyte function is tuned to social experience and identifies a social-context-specific mechanism by which astrocytic TRPA1 and GABA coordinately suppress hippocampal circuit function.

Effects of acute moderate-intensity exercise on executive function in children with preterm birth: A randomized crossover study.

BACKGROUND: Acute exercise appears to promote executive function (EF) in children. However, the effect of acute exercise on EF in children with preterm birth (PB) remains unclear. OBJECTIVE: To investigate whether acute moderate-intensity exercise improves EF in children with PB. METHODS: Twenty child participants with PB (age = 10.95 ± 1.19 years, birth age = 31.71 ± 3.64 weeks) completed exercise and control sessions in a randomized crossover design. In the exercise session, participants completed a 30-minute period of moderate-intensity aerobic exercise. In the control session, participants watched a video for appropriately 30 min. Following each session immediately, inhibitory control, an aspect of EF, was assessed with the Numerical Stroop task. RESULTS: Response time (RT) for the Stroop's incongruent condition was shorter after the exercise session than after the control session. However, no differences were observed in RT for the congruent condition. Accuracy rate (ACC) in both congruent and incongruent conditions did not differ between exercise and control session. CONCLUSION: The findings support the beneficial effect of acute exercise on executive function (EF) in children with PB, particularly in terms of improving inhibitory control.

Inhibitory input directs astrocyte morphogenesis through glial GABA B R.

Communication between neurons and glia plays an important role in establishing and maintaining higher order brain function. Astrocytes are endowed with complex morphologies which places their peripheral processes in close proximity to neuronal synapses and directly contributes to their regulation of brain circuits. Recent studies have shown that excitatory neuronal activity promotes oligodendrocyte differentiation; whether inhibitory neurotransmission regulates astrocyte morphogenesis during development is unknown. Here we show that inhibitory neuron activity is necessary and sufficient for astrocyte morphogenesis. We found that input from inhibitory neurons functions through astrocytic GABA B R and that its deletion in astrocytes results in a loss of morphological complexity across a host of brain regions and disruption of circuit function. Expression of GABA B R in developing astrocytes is regulated in a region-specific manner by SOX9 or NFIA and deletion of these transcription factors results in region-specific defects in astrocyte morphogenesis, which is conferred by interactions with transcription factors exhibiting region-restricted patterns of expression. Together our studies identify input from inhibitory neurons and astrocytic GABA B R as universal regulators of morphogenesis, while further revealing a combinatorial code of region-specific transcriptional dependencies for astrocyte development that is intertwined with activity-dependent processes.

Activity-dependent induction of astrocytic Slc22a3 regulates sensory processing through histone serotonylation.

Neuronal activity drives global alterations in gene expression within neurons, yet how it directs transcriptional and epigenomic changes in neighboring astrocytes in functioning circuits is unknown. Here we show that neuronal activity induces widespread transcriptional upregulation and downregulation in astrocytes, highlighted by the identification of a neuromodulator transporter Slc22a3 as an activity-inducible astrocyte gene regulating sensory processing in the olfactory bulb. Loss of astrocytic Slc22a3 reduces serotonin levels in astrocytes, leading to alterations in histone serotonylation. Inhibition of histone serotonylation in astrocytes reduces expression of GABA biosynthetic genes and GABA release, culminating in olfactory deficits. Our study reveals that neuronal activity orchestrates transcriptional and epigenomic responses in astrocytes, while illustrating new mechanisms for how astrocytes process neuromodulatory input to gate neurotransmitter release for sensory processing.