RESUMO
To understand biological processes, it is necessary to reveal the molecular heterogeneity of cells by gaining access to the location and interaction of all biomolecules. Significant advances were achieved by super-resolution microscopy, but such methods are still far from reaching the multiplexing capacity of proteomics. Here, we introduce secondary label-based unlimited multiplexed DNA-PAINT (SUM-PAINT), a high-throughput imaging method that is capable of achieving virtually unlimited multiplexing at better than 15 nm resolution. Using SUM-PAINT, we generated 30-plex single-molecule resolved datasets in neurons and adapted omics-inspired analysis for data exploration. This allowed us to reveal the complexity of synaptic heterogeneity, leading to the discovery of a distinct synapse type. We not only provide a resource for researchers, but also an integrated acquisition and analysis workflow for comprehensive spatial proteomics at single-protein resolution.
Assuntos
Proteômica , Imagem Individual de Molécula , DNA , Microscopia de Fluorescência/métodos , Neurônios , ProteínasRESUMO
Current treatments of anxiety and depressive disorders are plagued by considerable side effects and limited efficacies, underscoring the need for additional molecular targets that can be leveraged to improve medications. Here, we have identified a molecular cascade triggered by chronic stress that exacerbates anxiety- and depressive-like behaviors. Specifically, chronic stress enhances Src kinase activity and tyrosine phosphorylation of calmodulin, which diminishes MyosinVa (MyoVa) interaction with Neuroligin2 (NL2), resulting in decreased inhibitory transmission and heightened anxiety-like behaviors. Importantly, pharmacological inhibition of Src reinstates inhibitory synaptic deficits and effectively reverses heightened anxiety-like behaviors in chronically stressed mice, a process requiring the MyoVa-NL2 interaction. These data demonstrate the reversibility of anxiety- and depressive-like phenotypes at both molecular and behavioral levels and uncover a therapeutic target for anxiety and depressive disorders.
Assuntos
Ansiedade , Calmodulina , Transdução de Sinais , Estresse Psicológico , Animais , Camundongos , Transdução de Sinais/efeitos dos fármacos , Ansiedade/tratamento farmacológico , Ansiedade/metabolismo , Estresse Psicológico/metabolismo , Calmodulina/metabolismo , Quinases da Família src/metabolismo , Fosforilação , Miosinas/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Depressão/tratamento farmacológico , Depressão/metabolismo , HumanosRESUMO
Ribbon synapses between inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs) in the inner ear are damaged by noise trauma and with aging, causing "synaptopathy" and hearing loss. Cocultures of neonatal denervated organs of Corti and newly introduced SGNs have been developed to find strategies for improving IHC synapse regeneration, but evidence of the physiological normality of regenerated synapses is missing. This study utilizes IHC optogenetic stimulation and SGN recordings, showing that, when P3-5 denervated organs of Corti are cocultured with SGNs, newly formed IHC/SGN synapses are indeed functional, exhibiting glutamatergic excitatory postsynaptic currents. When using older organs of Corti at P10-11, synaptic activity probed by deconvolution showed more mature release properties, closer to the specialized mode of IHC synaptic transmission crucial for coding the sound signal. This functional assessment of newly formed IHC synapses developed here, provides a powerful tool for testing approaches to improve synapse regeneration.
Assuntos
Gânglio Espiral da Cóclea , Sinapses , Animais , Gânglio Espiral da Cóclea/citologia , Gânglio Espiral da Cóclea/fisiologia , Sinapses/fisiologia , Camundongos , Células Ciliadas Auditivas Internas/fisiologia , Células Ciliadas Auditivas Internas/metabolismo , Transmissão Sináptica/fisiologia , Neurônios/fisiologia , Neurônios/metabolismo , Regeneração/fisiologia , Células Ciliadas Auditivas/fisiologia , Técnicas de Cocultura/métodos , Optogenética/métodos , Regeneração Nervosa/fisiologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Órgão Espiral/fisiologia , Órgão Espiral/citologia , Órgão Espiral/metabolismoRESUMO
Microglia sculpt developing neural circuits by eliminating excess synapses in a process called synaptic pruning, by removing apoptotic neurons, and by promoting neuronal survival. To elucidate the role of microglia during embryonic and postnatal brain development, we used a mouse model deficient in microglia throughout life by deletion of the fms-intronic regulatory element (FIRE) in the Csf1r locus. Surprisingly, young adult Csf1rΔFIRE/ΔFIRE mice display no changes in excitatory and inhibitory synapse number and spine density of CA1 hippocampal neurons compared with Csf1r+/+ littermates. However, CA1 neurons are less excitable, receive less CA3 excitatory input and show altered synaptic properties, but this does not affect novel object recognition. Cytokine profiling indicates an anti-inflammatory state along with increases in ApoE levels and reactive astrocytes containing synaptic markers in Csf1rΔFIRE/ΔFIRE mice. Notably, these changes in Csf1rΔFIRE/ΔFIRE mice closely resemble the effects of acute microglial depletion in adult mice after normal development. Our findings suggest that microglia are not mandatory for synaptic pruning, and that in their absence pruning can be achieved by other mechanisms.
Assuntos
Hipocampo , Microglia , Sinapses , Animais , Microglia/metabolismo , Sinapses/metabolismo , Camundongos , Hipocampo/metabolismo , Hipocampo/citologia , Espinhas Dendríticas/metabolismo , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/metabolismo , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética , Plasticidade Neuronal , Neurônios/metabolismo , Ácido Glutâmico/metabolismoRESUMO
It is well established that, during neural circuit development, glutamatergic synapses become strengthened via NMDA receptor (NMDAR)-dependent upregulation of AMPA receptor (AMPAR)-mediated currents. In addition, however, it is known that the neuromodulator serotonin is present throughout most regions of the vertebrate brain while synapses are forming and being shaped by activity-dependent processes. This suggests that serotonin may modulate or contribute to these processes. Here, we investigate the role of serotonin in the developing retinotectal projection of the Xenopus tadpole. We altered endogenous serotonin transmission in stage 48/49 (â¼10-21â days postfertilization) Xenopus tadpoles and then carried out a set of whole-cell electrophysiological recordings from tectal neurons to assess retinotectal synaptic transmission. Because tadpole sex is indeterminate at these early stages of development, experimental groups were composed of randomly chosen tadpoles. We found that pharmacologically enhancing and reducing serotonin transmission for 24â h up- and downregulates, respectively, AMPAR-mediated currents at individual retinotectal synapses. Inhibiting 5-HT2 receptors also significantly weakened AMPAR-mediated currents and abolished the synapse strengthening effect seen with enhanced serotonin transmission, indicating a 5-HT2 receptor-dependent effect. We also determine that the serotonin-dependent upregulation of synaptic AMPAR currents was mediated via an NMDAR-independent, PI3K-dependent mechanism. Altogether, these findings indicate that serotonin regulates AMPAR currents at developing synapses independent of NMDA transmission, which may explain its role as an enabler of activity-dependent plasticity.
Assuntos
Fosfatidilinositol 3-Quinases , Serotonina , Sinapses/fisiologia , Neurônios/fisiologia , Transmissão Sináptica/fisiologia , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores de AMPA/metabolismo , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol PropiônicoRESUMO
Latrophilin-1 (Lphn1, aka CIRL1 and CL1; gene symbol Adgrl1) is an adhesion GPCR that has been implicated in excitatory synaptic transmission as a candidate receptor for α-latrotoxin. Here we analyzed conditional knock-in/knock-out mice for Lphn1 that contain an extracellular myc epitope tag. Mice of both sexes were used in all experiments. Surprisingly, we found that Lphn1 is localized in cultured neurons to synaptic nanoclusters that are present in both excitatory and inhibitory synapses. Conditional deletion of Lphn1 in cultured neurons failed to elicit a detectable impairment in excitatory synapses but produced a decrease in inhibitory synapse numbers and synaptic transmission that was most pronounced for synapses close to the neuronal soma. No changes in axonal or dendritic outgrowth or branching were observed. Our data indicate that Lphn1 is among the few postsynaptic adhesion molecules that are present in both excitatory and inhibitory synapses and that Lphn1 by itself is not essential for excitatory synaptic transmission but is required for some inhibitory synaptic connections.
Assuntos
Camundongos Knockout , Receptores de Peptídeos , Sinapses , Animais , Feminino , Masculino , Camundongos , Células Cultivadas , Potenciais Pós-Sinápticos Excitadores/fisiologia , Hipocampo/metabolismo , Hipocampo/citologia , Potenciais Pós-Sinápticos Inibidores/fisiologia , Camundongos Endogâmicos C57BL , Inibição Neural/fisiologia , Neurônios/metabolismo , Neurônios/fisiologia , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores de Peptídeos/genética , Receptores de Peptídeos/metabolismo , Sinapses/metabolismo , Sinapses/fisiologia , Transmissão Sináptica/fisiologiaRESUMO
NMDA-type glutamate receptors (NMDARs) are widely recognized as master regulators of synaptic plasticity, most notably for driving long-term changes in synapse size and strength that support learning. NMDARs are unique among neurotransmitter receptors in that they require binding of both neurotransmitter (glutamate) and co-agonist (e.g., d-serine) to open the receptor channel, which leads to the influx of calcium ions that drive synaptic plasticity. Over the past decade, evidence has accumulated that NMDARs also support synaptic plasticity via ion flux-independent (non-ionotropic) signaling upon the binding of glutamate in the absence of co-agonist, although conflicting results have led to significant controversy. Here, we hypothesized that a major source of contradictory results might be attributed to variable occupancy of the co-agonist binding site under different experimental conditions. To test this hypothesis, we manipulated co-agonist availability in acute hippocampal slices from mice of both sexes. We found that enzymatic scavenging of endogenous co-agonists enhanced the magnitude of long-term depression (LTD) induced by non-ionotropic NMDAR signaling in the presence of the NMDAR pore blocker MK801. Conversely, a saturating concentration of d-serine completely inhibited LTD and spine shrinkage induced by glutamate binding in the presence of MK801 or Mg2+ Using a Förster resonance energy transfer (FRET)-based assay in cultured neurons, we further found that d-serine completely blocked NMDA-induced conformational movements of the GluN1 cytoplasmic domains in the presence of MK801. Our results support a model in which d-serine availability serves to modulate NMDAR signaling and synaptic plasticity even when the NMDAR is blocked by magnesium.
Assuntos
Hipocampo , Receptores de N-Metil-D-Aspartato , Serina , Transdução de Sinais , Animais , Receptores de N-Metil-D-Aspartato/metabolismo , Camundongos , Masculino , Feminino , Serina/metabolismo , Serina/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Camundongos Endogâmicos C57BL , Depressão Sináptica de Longo Prazo/efeitos dos fármacos , Depressão Sináptica de Longo Prazo/fisiologia , Ácido Glutâmico/metabolismo , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismoRESUMO
DiOlistic labelling is a robust, unbiased ballistic method that utilises lipophilic dyes to morphologically label neurons. While its efficacy on freshly dissected tissue specimens is well-documented, applying DiOlistic labelling to stored, fixed brain tissue and its use in polychromatic multi-marker studies poses significant technical challenges. Here, we present an improved, step-by-step protocol for DiOlistic labelling of dendrites and dendritic spines in fixed mouse tissue. Our protocol encompasses the five key stages: Tissue Preparation, Dye Bullet Preparation, DiOlistic Labelling, Confocal Imaging, and Image Analysis. This method ensures reliable and consistent labelling of dendritic spines in fixed mouse tissue, combined with increased throughput of samples and multi-parameter staining and visualisation of tissue, thereby offering a valuable approach for neuroscientific research.
Assuntos
Espinhas Dendríticas , Microscopia Confocal , Coloração e Rotulagem , Animais , Espinhas Dendríticas/ultraestrutura , Camundongos , Coloração e Rotulagem/métodos , Microscopia Confocal/métodos , Neurônios/citologia , Fixação de Tecidos/métodos , Encéfalo/citologiaRESUMO
Artificial synapses and bionic neurons offer great potential in highly efficient computing paradigms. However, complex requirements for specific electronic devices in neuromorphic computing have made memristors face the challenge of process simplification and universality. Herein, reconfigurable Ag/HfO2/NiO/Pt memristors are designed for feasible switching between volatile and nonvolatile modes by compliance current controlled Ag filaments, which enables stable and reconfigurable synaptic and neuronal functions. A neuromorphic computing system effectively replicates the biological synaptic weight alteration and continuously accomplishes excitation and reset of artificial neurons, which consist of bionic synapses and artificial neurons based on isotype Ag/HfO2/NiO/Pt memristors. This reconfigurable electrical performance of the Ag/HfO2/NiO/Pt memristors takes advantage of simplified hardware design and delivers integrated circuits with high density, which exhibits great potency for future neural networks.
RESUMO
Exploring multiple states based on the domain wall (DW) position has garnered increased attention for in-memory computing applications, particularly focusing on the utilization of spin-orbit torque (SOT) to drive DW motion. However, devices relying on the DW position require efficient DW pinning. Here, we achieve granular magnetization switching by incorporating an HfOx insertion layer between the Co/Ti interface. This corresponds to a transition in the switching model from the DW motion to DW nucleation. Compared to the conventional Pt/Co/Ti structure, incorporation of the HfOx layer results in an enhanced SOT efficiency and a lower switching current density. We also realized stable multistate storage and synaptic plasticity by applying pulse current in the Pt/Co/HfOx/Ti device. The simulation of artificial neural networks (ANN) based on the device can perform digital recognition tasks with an accuracy rate of 91%. These results identify that DW nucleation with a Pt/Co/HfOx/Ti based device has potential applications in multistate storage and ANN.
RESUMO
Reliably discerning real human faces from fake ones, known as antispoofing, is crucial for facial recognition systems. While neuromorphic systems offer integrated sensing-memory-processing functions, they still struggle with efficient antispoofing techniques. Here we introduce a neuromorphic facial recognition system incorporating multidimensional deep ultraviolet (DUV) optoelectronic synapses to address these challenges. To overcome the complexity and high cost of producing DUV synapses using traditional wide-bandgap semiconductors, we developed a low-temperature (≤70 °C) solution process for fabricating DUV synapses based on PEA2PbBr4/C8-BTBT heterojunction field-effect transistors. This method enables the large-scale (4-in.), uniform, and transparent production of DUV synapses. These devices respond to both DUV and visible light, showing multidimensional features. Leveraging the unique ability of the multidimensional DUV synapse (MDUVS) to discriminate real human skin from artificial materials, we have achieved robust neuromorphic facial recognition with antispoofing capability, successfully identifying genuine human faces with an accuracy exceeding 92%.
RESUMO
Functionally diverse devices with artificial neuron and synapse properties are critical for neuromorphic systems. We present a two-terminal artificial leaky-integrate-fire (LIF) neuron based on 6 nm Hf0.1Zr0.9O2 (HZO) antiferroelectric (AFE) thin films and develop a synaptic device through work function (WF) engineering. LIF neuron characteristics, including integration, firing, and leakage, are achieved in W/HZO/W devices due to the accumulated polarization and spontaneous depolarization of AFE HZO films. By engineering the top electrode with asymmetric WFs, we found that Au/Ti/HZO/W devices exhibit synaptic weight plasticity, such as paired-pulse facilitation and long-term potentiation/depression, achieving >90% accuracy in digit recognition within constructed artificial neural network systems. These findings suggest that AFE HZO capacitor-based neurons and WF-engineered artificial synapses hold promise for constructing efficient spiking neuron networks and artificial neural networks, thereby advancing neuromorphic computing applications based on emerging AFE HZO devices.
RESUMO
Huanglian Jiedu decoction (HLJD) has been used to treat ischemic stroke in clinic. However, the detailed protective mechanisms of HLJD on ischemic stroke have yet to be elucidated. The aim of this study is to elucidate the underlying pharmacological mechanisms of HLJD based on the inhibition of neuroinflammation and the amelioration of nerve cell damage. A middle cerebral artery occlusion reperfusion (MCAO/R) model was established in rats and received HLJD treatment. Effects of HLJD on neurological function was assessed based on Bederson's score, postural reflex test and asymmetry score. 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining, Hematein and eosin (HE) and Nissl staining were used to observe the pathological changes in brain. Then, transcriptomics was used to screen the differential genes in brain tissue in MCAO/R model rats following HLJD intervention. Subsequently, the effects of HLJD on neutrophil extracellular trap (NET) formation-related neuroinflammation, gamma-aminobutyric acid (GABA)ergic synapse activation, nerve cell damage and proliferation were validated using immunofluorescence, western blot and enzyme-linked immunosorbent assay (ELISA). Our results showed that HLJD intervention reduced the Bederson's score, postural reflex test score and asymmetry score in MCAO/R model rats. Pathological staining indicated that HLJD treatment decreased the cerebral infarction area, mitigated neuronal damage and increased the numbers of Nissl bodies. Transcriptomics suggested that HLJD affected 435 genes in MCAO/R rats. Among them, several genes involving in NET formation and GABAergic synapses pathways were dysregulated. Subsequent experimental validation showed that HLJD reduced the MPO+CitH3+ positive expression area, reduced the protein expression of PAD4, p-P38/P38, p-ERK/ERK and decreased the levels of IL-1ß, IL-6 and TNF-α, reversed the increase of Iba1+TLR4+, Iba1+p65+ and Iba1+NLRP3+ positive expression area in brain. Moreover, HLJD increased GABA levels, elevated the protein expression of GABRG1 and GAT3, decreased the TUNEL positive expression area and increased the Ki67 positive expression area in brain. HLJD intervention exerts a multifaceted positive impact on ischemia-induced cerebral injury in MCAO/R rats. This intervention effectively inhibits neuroinflammation by mitigating NET formation, and concurrently improves nerve cell damage and fosters nerve cell proliferation through activating GABAergic synapses.
Assuntos
Isquemia Encefálica , Medicamentos de Ervas Chinesas , Ratos Sprague-Dawley , Sinapses , Animais , Medicamentos de Ervas Chinesas/farmacologia , Ratos , Masculino , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Isquemia Encefálica/metabolismo , Isquemia Encefálica/tratamento farmacológico , Modelos Animais de Doenças , Neurônios GABAérgicos/metabolismo , Neurônios GABAérgicos/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismo , Infarto da Artéria Cerebral Média/complicações , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/complicações , Fármacos Neuroprotetores/farmacologia , Encéfalo/patologia , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacosRESUMO
Thrombospondins (TSPs) are astrocyte-secreted extracellular matrix proteins that play key roles as regulators of synaptogenesis in the central nervous system. We previously showed that TSP1/2 are upregulated in the partial neocortical isolation model ("undercut" or "UC" below) of posttraumatic epileptogenesis and may contribute to abnormal axonal sprouting, aberrant synaptogenesis and epileptiform discharges in the UC cortex. These results led to the hypothesis that posttraumatic epileptogeneis would be reduced in TSP1/2 knockout (TSP1/2 KO) mice. To test the hypothesis, we made UC lesions at P21, and subsequent experiments were conducted 14d later at P35. Ex vivo extracellular single or multi-electrode field potential recordings were obtained from layer V in cortical slices at P35 and in vivo video-EEGs of spontaneous epileptiform bursts were recorded to examine the effect of TSP1/2 deletion on epileptogenesis following cortical injury. Immunohistochemical experiments were performed to assess the effect of TSP1/2 KOâ¯+â¯UC on the number of putative excitatory synapses and the expression of TSP4 and HEVIN, other astrocytic proteins known to up-regulate excitatory synapse formation. Unexpectedly, our results showed that, compared with WTâ¯+â¯UC mice, TSP1/2 KOâ¯+â¯UC mice displayed increased epileptiform activity, as indicated by 1) increased incidence and more rapid propagation of evoked and spontaneous epileptiform discharges in UC neocortical slices; 2) increased occurrence of spontaneous epileptiform discharges in vivo. There was an associated increase in the density of VLUT1/PSD95-IR colocalizations (putative excitatory synapses) and significantly upregulated TSP4- and HEVIN-IR in TSP1/2 KOâ¯+â¯UC versus WTâ¯+â¯UC mice. Results suggest that TSP1/2 deletion plays a potential epileptogenic role following neocortical injury, associated with compensatory upregulation of TSP4 and HEVIN, which may contribute to the increase in the density of excitatory synapses and resulting neural network hyperexcitability.
RESUMO
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, involving the selective degeneration of cortical upper synapses in the primary motor cortex (M1). Excitotoxicity in ALS occurs due to an imbalance between excitation and inhibition, closely linked to the loss/gain of astrocytic function. Using the ALS SOD1G93A mice, we investigated the astrocytic contribution for the electrophysiological alterations observed in the M1 of SOD1G93A mice, throughout disease progression. Results showed that astrocytes are involved in synaptic dysfunction observed in presymptomatic SOD1G93A mice, since astrocytic glutamate transport currents are diminished and pharmacological inhibition of astrocytes only impaired long-term potentiation and basal transmission in wild-type mice. Proteomic analysis revealed major differences in neuronal transmission, metabolism, and immune system in upper synapses, confirming early communication deficits between neurons and astroglia. These results provide valuable insights into the early impact of upper synapses in ALS and the lack of supportive functions of cortical astrocytes, highlighting the possibility of manipulating astrocytes to improve synaptic function.
Assuntos
Esclerose Lateral Amiotrófica , Córtex Motor , Doenças Neurodegenerativas , Camundongos , Animais , Astrócitos/metabolismo , Esclerose Lateral Amiotrófica/metabolismo , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo , Camundongos Transgênicos , Doenças Neurodegenerativas/metabolismo , Proteômica , Modelos Animais de Doenças , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismoRESUMO
Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) are characterized by neuronal α-synuclein (α-syn) inclusions termed Lewy Pathology, which are abundant in the amygdala. The basolateral amygdala (BLA), in particular, receives projections from the thalamus and cortex. These projections play a role in cognition and emotional processing, behaviors which are impaired in α-synucleinopathies. To understand if and how pathologic α-syn impacts the BLA requires animal models of α-syn aggregation. Injection of α-syn pre-formed fibrils (PFFs) into the striatum induces robust α-syn aggregation in excitatory neurons in the BLA that corresponds with reduced contextual fear conditioning. At early time points after aggregate formation, cortico-amygdala excitatory transmission is abolished. The goal of this project was to determine if α-syn inclusions in the BLA induce synaptic degeneration and/or morphological changes. In this study, we used C57BL/6 J mice injected bilaterally with PFFs in the dorsal striatum to induce α-syn aggregate formation in the BLA. A method was developed using immunofluorescence and three-dimensional reconstruction to analyze excitatory cortico-amygdala and thalamo-amygdala presynaptic terminals closely juxtaposed to postsynaptic densities. The abundance and morphology of synapses were analyzed at 6- or 12-weeks post-injection of PFFs. α-Syn aggregate formation in the BLA did not cause a significant loss of synapses, but cortico-amygdala and thalamo-amygdala presynaptic terminals and postsynaptic densities with aggregates of α-syn show increased volumes, similar to previous findings in human DLB cortex, and in non-human primate models of PD. Transmission electron microscopy showed that asymmetric synapses in mice with PFF-induced α-syn aggregates have reduced synaptic vesicle intervesicular distances, similar to a recent study showing phospho-serine-129 α-syn increases synaptic vesicle clustering. Thus, pathologic α-syn causes major alterations to synaptic architecture in the BLA, potentially contributing to behavioral impairment and amygdala dysfunction observed in synucleinopathies.
Assuntos
Complexo Nuclear Basolateral da Amígdala , Camundongos Endogâmicos C57BL , Sinapses , alfa-Sinucleína , Animais , Complexo Nuclear Basolateral da Amígdala/metabolismo , Complexo Nuclear Basolateral da Amígdala/patologia , alfa-Sinucleína/metabolismo , Sinapses/patologia , Sinapses/metabolismo , Camundongos , MasculinoRESUMO
Environmental enrichment (EE) has been shown to produce beneficial effects in addiction disorders; however, due to its configurational complexity, the underlying mechanisms are not yet fully elucidated. Recent evidence suggests that EE, acting as a metaplastic agent, may affect glutamatergic mechanisms underlying appetitive memory and, in turn, modulate reward-seeking behaviours: here, we have investigated such a possibility following a brief EE exposure. Adult male Sprague-Dawley rats were exposed to EE for 22 h and the expression of critical elements of the glutamate synapse was measured 2 h after the end of EE in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and hippocampus (Hipp) brain areas, which are critical for reward and memory. We focused our investigation on the expression of NMDA and AMPA receptor subunits, their scaffolding proteins SAP102 and SAP97, vesicular and membrane glutamate transporters vGluT1 and GLT-1, and critical structural components such as proteins involved in morphology and function of glutamatergic synapses, PSD95 and Arc/Arg3.1. Our findings demonstrate that a brief EE exposure induces metaplastic changes in glutamatergic mPFC, NAc and Hipp. Such changes are area-specific and involve postsynaptic NMDA/AMPA receptor subunit composition, as well as changes in the expression of their main scaffolding proteins, thus influencing the retention of such receptors at synaptic sites. Our data indicate that brief EE exposure is sufficient to dynamically modulate the glutamatergic synapses in mPFC-NAc-Hipp circuits, which may modulate rewarding and memory processes.
Assuntos
Ácido Glutâmico , Receptores de AMPA , Ratos , Animais , Masculino , Ácido Glutâmico/metabolismo , Ratos Sprague-Dawley , Receptores de AMPA/metabolismo , N-Metilaspartato/farmacologia , Sinapses/fisiologia , Núcleo Accumbens , Receptores de N-Metil-D-Aspartato/metabolismoRESUMO
2D Ruddlesden-Popper phase layered perovskites (RPLPs) hold great promise for optoelectronic applications. In this study, a series of high-performance heterojunction phototransistors (HPTs) based on RPLPs with different organic spacer cations (namely butylammonium (BA+), cyclohexylammonium (CyHA+), phenethylammonium (PEA+), p-fluorophenylethylammonium (p-F-PEA+), and 2-thiophenethylammonium (2-ThEA+)) are fabricated successfully, in which high-mobility organic semiconductor 2,7-dioctyl[1]benzothieno[3,2-b]benzothiophene is adopted to form type II heterojunction channels with RPLPs. The 2-ThEA+-RPLP-based HPTs show the highest photosensitivity of 3.18 × 107 and the best detectivity of 9.00 × 1018 Jones, while the p-F-PEA+-RPLP-based ones exhibit the highest photoresponsivity of 5.51 × 106 A W-1 and external quantum efficiency of 1.32 × 109%, all of which are among the highest reported values to date. These heterojunction systems also mimicked several optically controllable fundamental characteristics of biological synapses, including excitatory postsynaptic current, paired-pulse facilitation, and the transition from short-term memory to long-term memory states. The device based on 2-ThEA+-RPLP film shows an ultra-high PPF index of 234%. Moreover, spacer engineering brought fine-tuned thin film microstructures and efficient charge transport/transfer, which contributes to the superior photodetection performance and synaptic functions of these RPLP-based HPTs. In-depth structure-property correlations between the organic spacer cations/RPLPs and thin film microstructure/device performance are systematically investigated.
RESUMO
1D nanowire networks, sharing similarities of structure, information transfer, and computation with biological neural networks, have emerged as a promising platform for neuromorphic systems. Based on brain-like structures of 1D nanowire networks, neuromorphic synaptic devices can overcome the von Neumann bottleneck, achieving intelligent high-efficient sensing and computing function with high information processing rates and low power consumption. Here, high-temperature neuromorphic synaptic devices based on SiC@NiO core-shell nanowire networks optoelectronic memristors (NNOMs) are developed. Experimental results demonstrate that NNOMs attain synaptic short/long-term plasticity and modulation plasticity under both electrical and optical stimulation, and exhibit advanced functions such as short/long-term memory and "learning-forgetting-relearning" under optical stimulation at both room temperature and 200 °C. Based on the advanced functions under light stimulus, the constructed 5 × 3 optoelectronic synaptic array devices exhibit a stable visual memory function up to 200 °C, which can be utilized to develop artificial visual systems. Additionally, when exposed to multiple electronic or optical stimuli, the NNOMs effectively replicate the principles of Pavlovian classical conditioning, achieving visual heterologous synaptic functionality and refining neural networks. Overall, with abundant synaptic characteristics and high-temperature thermal stability, these neuromorphic synaptic devices offer a promising route for advancing neuromorphic computing and visual systems.
RESUMO
Artificial optoelectronic synapses (OES) have attracted extensive attention in brain-inspired information processing and neuromorphic computing. However, OES at near-infrared wavelengths have rarely been reported, seriously limiting the application in modern optical communication. Herein, high-performance near-infrared OES devices based on VO2/MoO3 heterojunctions are presented. The textured MoO3 films are deposited on the sputtered VO2 film by using the glancing-angle deposition technique to form a heterojunction device. Through tuning the oxygen defects in the VO2 film, the fabricated VO2/MoO3 heterojunction exhibits versatile electrical synaptic functions. Benefiting from the highly efficient light harvesting and the unique interface effect, the photonic synaptic characteristics, mainly including the short/long-term plasticity and learning experience behavior are successfully realized at the O (1342 nm) and C (1550 nm) optical communication wavebands. Moreover, a single OES device can output messages accurately by converting light signals of the Morse code to distinct synaptic currents. More importantly, a 3 × 3 artificial OES array is constructed to demonstrate the impressive image perceiving and learning capabilities. This work not only indicates the feasibility of defect and interface engineering in modulating the synaptic plasticity of OES devices, but also provides effective strategies to develop advanced artificial neuromorphic visual systems for next-generation optical communication systems.