This study evaluated the capacity of 23 multidrug-resistant (MDR) clinical isolates of Acinetobacter baumannii to adhere to respiratory epithelial cell surfaces and to form biofilm on a polystyrene ...surface. All 23 A. baumannii isolates were capable of adhering efficiently to respiratory epithelial cells, and biofilm production was positively associated with epithelial cell adhesiveness (r 0.80, p <0.0001). In the presence of the chelating agent EDTA, biofilm formation was markedly reduced. Cell adhesiveness and biofilm formation were significantly higher in isolates carrying the blaPER-1 gene as compared with isolates without this extended-spectrum β-lactamase gene (p <0.005 and p <0.001, respectively). Further examination by RT-PCR showed a positive correlation between the level of expression of the blaPER-1 gene and the level of biofilm formation (r 0.89, p <0.0001) and cell adhesiveness (r 0.74, p <0.006). Overall, the study demonstrated a high capacity of clinical isolates of MDR A. baumannii to form biofilm and to adhere to respiratory epithelial cells. This feature, combined with multidrug resistance, might contribute to the survival of these organisms and their dissemination in the hospital environment.
Low-intensity, low-frequency ultrasound (LILFU) is the next-generation, non-invasive brain stimulation technology for treating various neurological and psychiatric disorders. However, the underlying ...cellular and molecular mechanism of LILFU-induced neuromodulation has remained unknown. Here, we report that LILFU-induced neuromodulation is initiated by opening of TRPA1 channels in astrocytes. The Ca2+ entry through TRPA1 causes a release of gliotransmitters including glutamate through Best1 channels in astrocytes. The released glutamate activates NMDA receptors in neighboring neurons to elicit action potential firing. Our results reveal an unprecedented mechanism of LILFU-induced neuromodulation, involving TRPA1 as a unique sensor for LILFU and glutamate-releasing Best1 as a mediator of glia-neuron interaction. These discoveries should prove to be useful for optimization of human brain stimulation and ultrasonogenetic manipulations of TRPA1.
Display omitted
•Ultrasound-induced neuromodulation is initiated by opening of TRPA1 in astrocytes•The Ca2+ entry through TRPA1 causes a release of glutamate through Best1 channels•The released glutamate activates NMDA receptors in neighboring neurons
Oh et al. show that TRPA1 is the molecular sensor and transducer for low-intensity, low-frequency ultrasound (LILFU). With TRPA1’s unique co-localization and cooperation with the glutamate-releasing Ca2+-activated Best1 at the microdomains of astrocytes, LILFU is capable of eliciting neuromodulation as a consequence of neuronal NMDAR activation.
Astroglial cells were long considered as structural and metabolic supporting cells are which do not directly participate in information processing in the brain. Discoveries of responsiveness of ...astrocytes to synaptically-released glutamate and their capability to release agonists of glutamate receptors awakened extensive studies of glia-neuron communications and led to the revolutionary changes in our understanding of brain cellular networks. Nowadays, astrocytes are widely acknowledged as inseparable element of glutamatergic synapses and role for glutamatergic astrocyte-neuron interactions in the brain computation is emerging.
Astroglial glutamate receptors, in particular of NMDA, mGluR3 and mGluR5 types, can activate a variety of molecular cascades leading astroglial-driven modulation of extracellular levels of glutamate and activity of neuronal glutamate receptors. Their preferential location to the astroglial perisynaptic processes facilitates interaction of astrocytes with individual excitatory synapses. Bi-directional glutamatergic communication between astrocytes and neurons underpins a complex, spatially-distributed modulation of synaptic signalling thus contributing to the enrichment of information processing by the neuronal networks.
Still, further research is needed to bridge the substantial gaps in our understanding of mechanisms and physiological relevance of astrocyte-neuron glutamatergic interactions, in particular ability of astrocytes directly activate neuronal glutamate receptors by releasing glutamate and, arguably, d-Serine. An emerging roles for aberrant changes in glutamatergic astroglial signalling, both neuroprotective and pathogenic, in neurological and neurodegenerative diseases also require further investigation.
This article is part of the Neuropharmacology Special Issue on ‘Glutamate Receptors - The Glutamatergic Synapse’.
•Glutamate receptors underlie ability of astrocytes to detect neuronal activity.•Astroglial uptake and release of glutamate affect synaptic transmission and plasticity.•Astrocytic mGluR and NMDA receptors modulate activity of glutamate transporters.•Expression of glutamate receptors in astrocytes changes in pathological context.
Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a ...possible association between BD and the gene encoding phospholipase Cγ1 (PLCG1), its etiological basis remains unclear. Here, we report that mice lacking phospholipase Cγ1 (PLCγ1) in the forebrain (Plcg1
; CaMKII) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses. Inhibitory transmission in hippocampal pyramidal neurons and striatal dopamine receptor D1-expressing neurons of Plcg1-deficient mice was significantly reduced. The decrease in inhibitory transmission is likely due to a reduced number of γ-aminobutyric acid (GABA)-ergic boutons, which may result from impaired localization and/or stabilization of postsynaptic CaMKII (Ca
/calmodulin-dependent protein kinase II) at inhibitory synapses. Moreover, mutant mice display impaired brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent synaptic plasticity in the hippocampus, which could account for deficits of spatial memory. Lithium and valproate, the drugs presently used to treat mania associated with BD, rescued the hyperactive phenotypes of Plcg1
; CaMKII mice. These findings provide evidence that PLCγ1 is critical for synaptic function and plasticity and that the loss of PLCγ1 from the forebrain results in manic-like behavior.
Successful exploitation of semiconductor nanocrystals (NCs) in commercial products is due to the remarkable progress in the wet-chemical synthesis and controlled assembly of NCs. Central to the ...cadence of this progress is the ability to understand how NC growth and assembly can be controlled kinetically and thermodynamically. The arrested precipitation strategy offers a wide opportunity for materials selection, size uniformity, and morphology control. In this colloidal approach, capping ligands play an instrumental role in determining growth parameters and inter-NC interactions. The impetus for exquisite control over the size and shape of NCs and orientation of NCs in an ensemble has called for the use of two or more types of ligands in the system. In multiple ligand approaches, ligands with different functionalities confer extended tunability, hinting at the possibility of atomic-precision growth and long-range ordering of desired superlattices. Here, we highlight the progress in understanding the roles of ligands in size and shape control and assembly of NCs. We discuss the implication of the advances in the context of optoelectronic applications.
The multiple ligands with different functionalities enable atomic-precision control of NCs morphology and subtle inter-NC interactions, which paves the way for novel optoelectronic applications.
Synaptically localized NMDA receptors (NMDARs) play a crucial role in important cognitive functions by mediating synaptic transmission and plasticity. In contrast, a tonic NMDAR current, thought to ...be mediated by extrasynaptic NMDARs, has a less clear function. This review provides a comprehensive overview of tonic NMDAR currents, focusing on their roles in synaptic transmission/plasticity and their impact on cognitive functions and psychiatric disorders. We discuss the roles of 3 endogenous ligands (i.e., glutamate, glycine, and D-serine) and receptors in mediating tonic NMDAR currents and explore the diverse mechanisms that regulate tonic NMDAR currents. In light of recent controversies surrounding the source of D-serine, we highlight the recent findings suggesting that astrocytes release D-serine to modulate tonic NMDAR currents and control cognitive flexibility. Furthermore, we propose distinct roles of neuronal and astrocytic D-serine in different locations and their implications for synaptic regulation and cognitive functions. The potential roles of tonic NMDAR currents in various psychiatric disorders, such as schizophrenia and autism spectrum disorder, are discussed in the context of the NMDAR hypofunction hypothesis. By presenting the mechanisms by which various cells, particularly astrocytes, regulate tonic NMDAR currents, we aim to stimulate future research in NMDAR hypofunction- or hyperfunction-related psychiatric disorders. This review not only provides a better understanding of the complex interplay between tonic NMDAR currents and cognitive functions but also sheds light on its potential therapeutic target for the treatment of various psychiatric disorders.
Growth of monodisperse indium phosphide (InP) quantum dots (QDs) represents a pressing demand in display applications, as size uniformity is related to color purity in display products. Here, we ...report the colloidal synthesis of InP QDs in the presence of Zn precursors in which size uniformity is markedly enhanced as compared to the case of InP QDs synthesized without Zn precursors. Nuclear magnetic resonance spectroscopy, X-ray photoelectron spectroscopy, and mass spectrometry analyses on aliquots taken during the synthesis allow us to monitor the appearance of metal–phosphorus complex intermediates in the growth of InP QDs. In the presence of zinc carboxylate, intermediate species containing Zn–P bonding appears. The Zn–P intermediate complex with P(SiMe3)3 exhibits lower reactivity than that of the In–P complex, which is corroborated by our prediction based on density functional theory and electrostatic potential charge analysis. The formation of a stable Zn–P intermediate complex results in lower reactivity, which enables slow growth of QDs and lowers the extreme reactivity of P(SiMe3)3, hence monodisperse QDs. Insights from experimental and theoretical studies advance mechanistic understanding and control of nucleation and growth of InP QDs, which are key to the preparation of monodisperse InP-based QDs in meeting the demand of the display market.
The underlying mechanisms of how positive emotional valence (e.g., pleasure) causes preference of an associated context is poorly understood. Here, we show that activation of astrocytic μ-opioid ...receptor (MOR) drives conditioned place preference (CPP) by means of specific modulation of astrocytic MOR, an exemplar endogenous Gi protein-coupled receptor (Gi-GPCR), in the CA1 hippocampus. Long-term potentiation (LTP) induced by a subthreshold stimulation with the activation of astrocytic MOR at the Schaffer collateral pathway accounts for the memory acquisition to induce CPP. This astrocytic MOR-mediated LTP induction is dependent on astrocytic glutamate released upon activation of the astrocytic MOR and the consequent activation of the presynaptic mGluR1. The astrocytic MOR-dependent LTP and CPP were recapitulated by a chemogenetic activation of astrocyte-specifically expressed Gi-DREADD hM4Di. Our study reveals that the transduction of inhibitory Gi-signaling into augmented excitatory synaptic transmission through astrocytic glutamate is critical for the acquisition of contextual memory for CPP.
Display omitted
•Hippocampal astrocytic μ-opioid receptor (MOR) activation drives conditioned place preference (CPP)•Astrocytic MOR activation enhances synaptic plasticity at the Schaffer collateral pathway•Chemogenetic activation of astrocytic Gi-DREADD recapitulates MOR-mediated LTP and CPP
Nam et al. demonstrate that activation of hippocampal astrocytic μ-opioid receptor causes glutamate release, which increases the release probability by neuronal presynaptic mGluR1 activation and potentiates synaptic plasticity at the SC-CA1 pathway. This enhanced synaptic transmission and synaptic plasticity account for the acquisition of memory associated with CPP.
Key points
Neuronal activity causes astrocytic volume change via K+ uptake through TREK‐1 containing two‐pore domain potassium channels.
The volume transient is terminated by Cl− efflux through the ...Ca2+‐activated anion channel BEST1.
The source of the Ca2+ required to open BEST1 appears to be the stretch‐activated TRPA1 channel.
Intense neuronal activity is synaptically coupled with a physical change in astrocytes via volume transients.
The brain volume changes dynamically and transiently upon intense neuronal activity through a tight regulation of ion concentrations and water movement across the plasma membrane of astrocytes. We have recently demonstrated that an intense neuronal activity and subsequent astrocytic AQP4‐dependent volume transient are critical for synaptic plasticity and memory. We have also pharmacologically demonstrated a functional coupling between synaptic activity and the astrocytic volume transient. However, the precise molecular mechanisms of how intense neuronal activity and the astrocytic volume transient are coupled remain unclear. Here we utilized an intrinsic optical signal imaging technique combined with fluorescence imaging using ion sensitive dyes and molecular probes and electrophysiology to investigate the detailed molecular mechanisms in genetically modified mice. We report that a brief synaptic activity induced by a train stimulation (20 Hz, 1 s) causes a prolonged astrocytic volume transient (80 s) via K+ uptake through TREK‐1 containing two‐pore domain potassium (K2P) channels, but not Kir4.1 or NKCC1. This volume change is terminated by Cl− efflux through the Ca2+‐activated anion channel BEST1, but not the volume‐regulated anion channel TTYH. The source of the Ca2+ required to open BEST1 appears to be the stretch‐activated TRPA1 channel in astrocytes, but not IP3R2. In summary, our study identifies several important astrocytic ion channels (AQP4, TREK‐1, BEST1, TRPA1) as the key molecules leading to the neuronal activity‐dependent volume transient in astrocytes. Our findings reveal new molecular and cellular mechanisms for the synaptic coupling of intense neuronal activity with a physical change in astrocytes via volume transients.
Key points
Neuronal activity causes astrocytic volume change via K+ uptake through TREK‐1 containing two‐pore domain potassium channels.
The volume transient is terminated by Cl− efflux through the Ca2+‐activated anion channel BEST1.
The source of the Ca2+ required to open BEST1 appears to be the stretch‐activated TRPA1 channel.
Intense neuronal activity is synaptically coupled with a physical change in astrocytes via volume transients.
Sensory discrimination is essential for survival. However, how sensory information is finely controlled in the brain is not well defined. Here, we show that astrocytes control tactile acuity via ...tonic inhibition in the thalamus. Mechanistically, diamine oxidase (DAO) and the subsequent aldehyde dehydrogenase 1a1 (Aldh1a1) convert putrescine into GABA, which is released via Best1. The GABA from astrocytes inhibits synaptically evoked firing at the lemniscal synapses to fine-tune the dynamic range of the stimulation-response relationship, the precision of spike timing, and tactile discrimination. Our findings reveal a novel role of astrocytes in the control of sensory acuity through tonic GABA release.
Display omitted
•Thalamic astrocytes synthesize GABA via DAO and Aldh1a1 to mediate tonic inhibition•Tonic GABA improves linearity and temporal fidelity of synaptically evoked TC firing•Astrocytic tonic GABA improves tactile discrimination performance
Kwak et al. report that astrocytes synthesize GABA using DAO and Aldh1a1 and release GABA through the Best1 channel to mediate tonic GABA in the thalamus. Astrocytic tonic GABA fine-tunes the dynamic range and precision of stimulation to response of TC firing, thus enhancing the performance of sensory discrimination of mice.
PDF
