Nanozyme Catalytic Performance Enhancement through Defect and Electronic Structure Regulation of Metal-Doped NiCo2O4@Pd.

Spinel oxides have emerged as a promising candidate in the realm of nanozymes with variable oxidation states, while their limited active sites and low conductivity hinder further application. In this work, we synthesize a series of metal-doped NiCo2O4 nanospheres decorated with Pd, which are deployed as highly efficient nanozymes for the detection of cancer biomarkers. Through meticulous modulation of the molar ratio between NiCo2O4 and Pd, we orchestrated precise control over the oxygen vacancies and electronic structure within the nanozymes, a key factor in amplifying the catalytic prowess. Leveraging the superior H2O2 reduction catalytic properties of Fe-NiCo2O4@Pd, we have successfully implemented its application in the electrochemical detection of biomarkers, achieving unparalleled analytical performance, much higher than that of Pd/C and other reported nanozymes. This research paves the way for innovative electron modification strategies in the design of high-performance nanozymes, presenting a formidable tool for clinical diagnostic analyses.

Effects of subthalamic nucleus deep brain stimulation using different frequency programming paradigms on axial symptoms in advanced Parkinson's disease.

BACKGROUND: In advanced Parkinson's disease (PD), axial symptoms are common and can be debilitating. Although deep brain stimulation (DBS) significantly improves motor symptoms, conventional high-frequency stimulation (HFS) has limited effectiveness in improving axial symptoms. In this study, we investigated the effects on multiple axial symptoms after DBS surgery with three different frequency programming paradigms comprising HFS, low-frequency stimulation (LFS), and variable-frequency stimulation (VFS). METHODS: This study involved PD patients who had significant preoperative axial symptoms and underwent bilateral subthalamic nucleus (STN) DBS. Axial symptoms, motor symptoms, medications, and quality of life were evaluated preoperatively (baseline). One month after surgery, HFS was applied. At 6 months post-surgery, HFS assessments were performed, and HFS was switched to LFS. A further month later, we conducted LFS assessments and switched LFS to VFS. At 8 months after surgery, VFS assessments were performed. RESULTS: Of the 21 PD patients initially enrolled, 16 patients were ultimately included in this study. Regarding HFS, all axial symptoms except for the Berg Balance Scale (p < 0.0001) did not improve compared with the baseline (all p > 0.05). As for LFS and VFS, all axial symptoms improved significantly compared with both the baseline and HFS (all p < 0.05). Moreover, motor symptoms and medications were significantly better than the baseline (all p < 0.05) after using LFS and VFS. Additionally, the quality of life of the PD patients after receiving LFS and VFS was significantly better than at the baseline and with HFS (all p < 0.0001). CONCLUSION: Our findings indicate that HFS is ineffective at improving the majority of axial symptoms in advanced PD. However, both the LFS and VFS programming paradigms exhibit significant improvements in various axial symptoms.

Temperature Effects on Electrochemical Energy-Storage Materials: A Case Study of Yttrium Niobate Porous Microspheres.

Lithium-ion batteries (LIBs) are very popular electrochemical energy-storage devices. However, their applications in extreme environments are hindered because their low- and high-temperature electrochemical performance is currently unsatisfactory. In order to build all-climate LIBs, it is highly desirable to fully understand the underlying temperature effects on electrode materials. Here, based on a novel porous-microspherical yttrium niobate (Y0.5 Nb24.5 O62 ) model material, this work demonstrates that the operation temperature plays vital roles in electrolyte decomposition on electrode-material surfaces, electrochemical kinetics, and crystal-structure evolution. When the operation temperature increases, the reaction between the electrolyte and the electrode material become more intensive, causing the formation of thicker solid electrolyte interface (SEI) films, which decreases the initial Coulombic efficiency. Meanwhile, the electrochemical kinetics becomes faster, leading to the larger reversible capacity, higher rate capability, and more suitable working potential (i.e., lower working potential for anodes and higher working potential for cathodes). Additionally, the maximum unit-cell-volume change becomes larger, resulting in poorer cyclic stability. The insight gains here can provide a universal guide for the exploration of all-climate electrode materials and their modification methods.

Revealing Structural Insights of Solid Electrolyte Interphase in High-Concentrated Non-Flammable Electrolyte for Li Metal Batteries by Cryo-TEM.

High-concentrated non-flammable electrolytes (HCNFE) in lithium metal batteries prevent thermal runaway accidents, but the microstructure of their solid electrolyte interphase (SEI) remains largely unexplored, due to the lack of direct imaging tools. Herein, cryo-HRTEM is applied to directly visualize the native state of SEI at the atomic scale. In HCNFE, SEI has a uniform laminated crystalline-amorphous structure that can prevent further reaction between the electrolyte and lithium. The inorganic SEI component, Li2 S2 O7 , is precisely identified by cryo-HRTEM. Density functional theory (DFT) calculations demonstrate that the final Li2 S2 O7 phase has suitable natural transmission channels for Li-ion diffusion and excellent ionic conductivity of 1.2 × 10-5 S cm-1 .

Exploring the network effects of deep brain stimulation for rapid eye movement sleep behavior disorder in Parkinson's disease.

BACKGROUND: The research findings on the effects of subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) with Rapid Eye Movement Sleep Behavior Disorder (RBD) are inconsistent, and there is a lack of research on DBS electrode sites and their network effects for the explanation of the differences. Our objective is to explore the optimal stimulation sites (that is the sweet spot) and the brain network effects of STN-DBS for RBD in PD. METHODS: In this study, among the 50 PD patients who underwent STN-DBS treatment, 24 PD patients with RBD were screened. According to clinical scores and imaging data, the sweet spot of STN-DBS was analyzed in PD patients with RBD, and the optimal structure and functional network models of subthalamic stimulation were constructed. RESULTS: Bilateral STN-DBS can effectively improve the symptoms of RBD and other non-motor symptoms in 24 PD patients with RBD. RBD Questionnaire-Hong Kong (RBDQ-HK) score was 41.33 ± 17.45 at baseline and 30.83 ± 15.83 at 1-year follow-up, with statistical significance between them (P < 0.01). However, the MoCA score was an exception with a baseline of 22.04 ± 4.28 and a 1-year follow-up of 21.58 ± 4.33, showing no statistical significance (P = 0.12). The sweet spot and optimal network connectivity models for RBD improvement have been validated as effective. CONCLUSIONS: Bilateral STN-DBS can improve the symptoms of RBD in PD. There exist the sweet spot and brain network effects of bilateral STN-DBS in the treatment of PD with RBD. Our study also demonstrates that RBD is a brain network disease.

Electroencephalogram-Based Brain Connectivity Analysis in Prolonged Disorders of Consciousness.

Background: Prolonged disorders of consciousness (pDOC) are common in neurology and place a heavy burden on families and society. This study is aimed at investigating the characteristics of brain connectivity in patients with pDOC based on quantitative EEG (qEEG) and extending a new direction for the evaluation of pDOC. Methods: Participants were divided into a control group (CG) and a DOC group by the presence or absence of pDOC. Participants underwent magnetic resonance imaging (MRI) T1 three-dimensional magnetization with a prepared rapid acquisition gradient echo (3D-T1-MPRAGE) sequence, and video EEG data were collected. After calculating the power spectrum by EEG data analysis tool, DTABR ((δ + θ)/(α + ß) ratio), Pearson's correlation coefficient (Pearson r), Granger's causality, and phase transfer entropy (PTE), we performed statistical analysis between two groups. Finally, receiver operating characteristic (ROC) curves of connectivity metrics were made. Results: The proportion of power in frontal, central, parietal, and temporal regions in the DOC group was lower than that in the CG. The percentage of delta power in the DOC group was significantly higher than that in the CG, the DTABR in the DOC group was higher than that in the CG, and the value was inverted. The Pearson r of the DOC group was higher than that of CG. The Pearson r of the delta band (Z = -6.71, P < 0.01), theta band (Z = -15.06, P < 0.01), and alpha band (Z = -28.45, P < 0.01) were statistically significant. Granger causality showed that the intensity of directed connections between the two hemispheres in the DOC group at the same threshold was significantly reduced (Z = -82.43, P < 0.01). The PTE of each frequency band in the DOC group was lower than that in the CG. The PTE of the delta band (Z = -42.68, P < 0.01), theta band (Z = -56.79, P < 0.01), the alpha band (Z = -35.11, P < 0.01), and beta band (Z = -63.74, P < 0.01) had statistical significance. Conclusion: Brain connectivity analysis based on EEG has the advantages of being noninvasive, convenient, and bedside. The Pearson r of DTABR, delta, theta, and alpha bands, Granger's causality, and PTE of the delta, theta, alpha, and beta bands can be used as biological markers to distinguish between pDOC and healthy people, especially when behavior evaluation is difficult or ambiguous; it can supplement clinical diagnosis.

Na-K Alloy Anode for High-Performance Solid-State Sodium Metal Batteries.

Rechargeable solid-state Na metal batteries (SSNMB) can offer high operational safety and energy density. However, poor solid-solid contact between the electrodes and the electrolyte can dramatically increase interfacial resistance and Na dendrite formation, even at low current rates. Therefore, we developed a carbon-fiber-supported liquid Na-K alloy anode that ensures close anode-electrolyte contact, enabling superior cycle stability and rate capability. We then demonstrated the first cryogenic transmission electron microscopy (cryo-TEM) characterization of an SSNMB, capturing the evolution of solid-electrolyte interphase (SEI) and revealing both crystalline and amorphous phases, which could facilitate ion transport and prevent continuous side reactions. By enhancing contact between the Na-K alloy and solid-state electrolyte, these symmetric cells are capable of cycling for over 800 h without notable increased polarization and enable an unprecedented critical current density (CCD) at 40 mA cm-2. Our liquid Na-K alloy approach offers a promising strategic avenue toward commercial SSNMBs.

Enabling Ultrastable Alkali Metal Anodes by Artificial Solid Electrolyte Interphase Fluorination.

The high specific capacity of alkalic metal (Li, Na, and K) anodes has drawn widespread interest; however, the practical applications of alkalic metal anodes have been hampered by dendrite growth and interfacial instability, resulting in performance deterioration and even safety issues. Here, we describe a simple method for building tunable fluoride-based artificial solid-electrolyte interphase (SEI) from the fluorination reaction of alkali metals with a mild organic fluorinating reagent. Comprehensive characterization by advanced electron microscopes shows that the LiF-based artificial SEI adopts a crystal-glass structure, which enables efficient Li ion transport and improves structural integrity against the volume changes that occur during Li plating/stripping. Compared with bare Li anode, the ones with artificial SEI exhibit decreased voltage hysteresis, enhanced rate capability, and prolonged cycle life. This method is also applied to generate fluoride-based artificial SEI on Na and K metal anodes that brings significant improvement in battery performance.

Identification of potential immunologic resilience in the healing process of diabetic foot ulcers.

Diabetic foot ulcers (DFUs) are one of the most common and challenging complications of diabetes, yet our understanding of their pathogenesis remains limited. We collected gene expression data of DFU patients from public databases. Bioinformatics tools were applied for systematic analysis, including the identification of differentially expressed genes (DEGs), weighted gene co-expression network analysis (WGCNA) and enrichment analysis. We further used single-cell RNA sequencing to identify the distribution of different cell populations in DFU. Finally, key results were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and flow cytometry. We identified 217 DEGs between ulcerated and healthy skin, and 37 DEGs between healing ulcers and ulcers. WGCNA revealed that the cyan module had the highest positive correlation with healthy skin and negative correlation with ulcers. The black module had the highest negative correlation with healthy skin and positive correlation with ulcers. Enrichment analysis showed that the genes in the cyan module were mainly associated with complement and coagulation cascades, while the genes in the black module were mainly associated with the IL-17 signalling pathway. In addition, CD8 T cells were significantly lower in ulcers than in healthy and healing ulcers. By comparing marker genes of CD8 T cells, we identified key genes in the cyan and black modules and validated their expression using RT-qPCR. The proportion of CD8 T cells was increased in healing ulcers. Flow cytometry detected increased levels of CD8 T, B and natural killer cells in healing ulcers. CD8 T cells and related key genes play an important role in the healing process of DFU. The results of this study provide a new perspective for understanding the pathogenesis and treatment of DFU.

Catalytic Chemistry Derived Artificial Solid Electrolyte Interphase for Stable Lithium Metal Anodes Working at 20†mA cm-2 and 20†mAh cm-2.

A stable solid electrolyte interphase (SEI) layer is crucial for lithium metal anode (LMA) to survive in long-term cycling. However, chaotic structures and chemical inhomogeneity of natural SEI make LMA suffering from exasperating dendrite growth and severe electrode pulverization, which hinder the practical application of LMAs. Here, we design a catalyst-derived artificial SEI layer with an ordered polyamide-lithium hydroxide (PA-LiOH) bi-phase structure to modulate ion transport and enable dendrite-free Li deposition. The PA-LiOH layer can substantially suppress the volume changes of LMA during Li plating/stripping cycles, as well as alleviate the parasitic reactions between LMA and electrolyte. The optimized LMAs demonstrate excellent stability in Li plating/stripping cycles for over 1000 hours at an ultra-high current density of 20 mA cm-2 in Li||Li symmetric cells. A high coulombic efficiency up to 99.2 % in Li half cells in additive-free electrolytes is achieved even after 500 cycles at a current density of 1 mA cm-2 with a capacity of 1 mAh cm-2 .

A meningioma and breast carcinoma metastasis collision tumor.

Co-existence of meningioma and breast carcinoma metastasis in the type of collision tumor is uncommon in the brain. A 65-year-old female with a history of breast carcinoma suffered from a mass in posterior fossa of brain. After a craniotomy, the pathological specimen showed a collision tumor with breast cancer metastasis and meningioma. In the clinical setting of previously vague diagnosis in imaging, craniotomy for removal of the mass is more recommended if conditions permit. Only the rare tumor is identified in pathology for further follow-up and research.

Identification of the WRKY Gene Family and Characterization of Stress-Responsive Genes in Taraxacum kok-saghyz Rodin.

WRKY transcription factors present unusual research value because of their critical roles in plant physiological processes and stress responses. Taraxacum kok-saghyz Rodin (TKS) is a perennial herb of dandelion in the Asteraceae family. However, the research on TKS WRKY TFs is limited. In this study, 72 TKS WRKY TFs were identified and named. Further comparison of the core motifs and the structure of the WRKY motif was analyzed. These TFs were divided into three groups through phylogenetic analysis. Genes in the same group of TkWRKY usually exhibit a similar exon-intron structure and motif composition. In addition, virtually all the TKS WRKY genes contained several cis-elements related to stress response. Expression profiling of the TkWRKY genes was assessed using transcriptome data sets and Real-Time RT-PCR data in tissues during physiological development, under abiotic stress and hormonal treatments. For instance, the TkWRKY18, TkWRKY23, and TkWRKY38 genes were significantly upregulated during cold stress, whereas the TkWRKY21 gene was upregulated under heat-stress conditions. These results could provide a basis for further studies on the function of the TKS WRKY gene family and genetic amelioration of TKS germplasm.

Identification and Analysis of Stress-Associated Proteins (SAPs) Protein Family and Drought Tolerance of ZmSAP8 in Transgenic Arabidopsis.

Stress-associated proteins (SAPs), a class of A20/AN1 zinc finger proteins, play vital roles in plant stress response. However, investigation of SAPs in maize has been very limited. Herein, to better trace the evolutionary history of SAPs in maize and plants, 415 SAPs were identified in 33 plant species and four species of other kingdoms. Moreover, gene duplication mode exploration showed whole genome duplication contributed largely to SAP gene expansion in angiosperms. Phylogeny reconstruction was performed with all identified SAPs by the maximum likelihood (ML) method and the SAPs were divided into five clades. SAPs within the same clades showed conserved domain composition. Focusing on maize, nine ZmSAPs were identified. Further promoter cis-elements and stress-induced expression pattern analysis of ZmSAPs indicated that ZmSAP8 was a promising candidate in response to drought stress, which was the only AN1-AN1-C2H2-C2H2 type SAP in maize and belonged to clade I. Additionally, ZmSAP8 was located in the nucleus and had no transactivation activity in yeast. Overexpressing ZmSAP8 enhanced the tolerance to drought stress in Arabidopsis thaliana, with higher seed germination and longer root length. Our results should benefit the further functional characterization of ZmSAPs.

Two rapid and sensitive methods based on TaqMan qPCR and droplet digital PCR assay for quantitative detection of Bacillus subtilis in rhizosphere.

AIMS: Bacillus subtilis, a typical plant growth-promoting rhizobacteria, can benefit plant through promoting growth and reducing disease. The colonization intensity of B. subtilis in rhizosphere is a key factor for improving their effectiveness of field application. In this study, we developed a rapid and sensitive method for detecting B. subtilis in rhizosphere via TaqMan qPCR and droplet digital PCR (ddPCR) methods. METHODS AND RESULTS: The primers/probe set targeting gyrB gene could successfully distinguish B. subtilis from its close-related species. Both the TaqMan qPCR and ddPCR methods exhibited a good linear relationship in the sensitivity assay, suggesting the developed method was specific, effective and reliable. Finally, the two methods were used to detect the colonization dynamic of B. subtilis within Arabidopsis rhizosphere. Both of them showed a consistent trend compared with the traditional cultivation-based and microscopy-based methods. CONCLUSIONS: The TaqMan qPCR and droplet digital PCR (ddPCR) methods we developed could be used to rapidly detect B. subtilis in rhizosphere. SIGNIFICANCE AND IMPACT OF THE STUDY: The TaqMan qPCR and ddPCR methods developed in this study can be applied to rapid quantitative detection of B. subtilis populations, and will be helpful to evaluate their effectiveness of field application.

Nuclear factor I/B promotes colorectal cancer cell proliferation, epithelial-mesenchymal transition and 5-fluorouracil resistance.

Nuclear factor I/B (NFIB) is a widely studied transcription factor that participates in tumor progression; nevertheless, studies on NFIB in colorectal cancer (CRC) are limited. In our study, Western blot and RT-PCR analyses showed that NFIB was overexpressed in CRC tissues and cell lines, which was consistent with our bioinformatic analysis results. Furthermore, NFIB expression was closely related to the TNM stage of CRC. NFIB promoted cell proliferation and migration and inhibited cell apoptosis in vitro. Meanwhile, we discovered that NFIB accelerated xenograft tumor growth in vivo. In addition, NFIB weakened the sensitivity of CRC cells to 5-fluorouracil (5-FU). NFIB induced epithelial-mesenchymal transition (EMT) by upregulating snail expression, which was accompanied by decreased E-cadherin and Zo-1 expression and increasedd Vimentin expression. Because the Akt pathway plays an important role in CRC progression, we examined whether there was a correlation between NFIB and the Akt pathway in cell proliferation and migration. Our results showed that NFIB promoted cell proliferation and increased 5-FU resistance by activating the Akt pathway. In summary, our findings suggested that NFIB induced EMT of CRC cells via upregulating snail expression and promoted cell proliferation and 5-FU resistance by activating the Akt pathway.

Prenatal Exposure to Alcohol Induces Functional and Structural Plasticity in Dopamine D1 Receptor-Expressing Neurons of the Dorsomedial Striatum.

BACKGROUND: Prenatal alcohol exposure (PAE) is a leading cause of hyperactivity in children. Excitation of dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) of the dorsomedial striatum (DMS), a brain region that controls voluntary behavior, is known to induce hyperactivity in mice. We therefore hypothesized that PAE-linked hyperactivity was due to persistently altered glutamatergic activity in DMS D1-MSNs. METHODS: Female Ai14 tdTomato reporter mice were given access to alcohol in an intermittent access, 2-bottle choice paradigm before pregnancy, and following mating with male D1-Cre mice, through the pregnancy period, and until postnatal day (P) 10. Locomotor activity was tested in juvenile (P21) and adult (P133) offspring, and alcohol-conditioned place preference (CPP) was measured in adult offspring. Glutamatergic activity in DMS D1-MSNs of adult PAE and control mice was measured by slice electrophysiology, followed by measurements of dendritic morphology. RESULTS: Our voluntary maternal alcohol consumption model resulted in increased locomotor activity in juvenile PAE mice, and this hyperactivity was maintained into adulthood. Furthermore, PAE resulted in a higher alcohol-induced CPP in adult offspring. Glutamatergic activity onto DMS D1-MSNs was also enhanced by PAE. Finally, PAE increased dendritic complexity in DMS D1-MSNs in adult offspring. CONCLUSIONS: Our model of PAE does result in persistent hyperactivity in offspring. In adult PAE offspring, hyperactivity is accompanied by potentiated glutamatergic strength and afferent connectivity in DMS D1-MSNs, an outcome that is also consistent with the observed increase in alcohol preference in PAE offspring. Consequently, a PAE-sensitive circuit, centered within the D1-MSN, may be linked to behavioral outcomes of PAE.

Dopamine D1 or D2 receptor-expressing neurons in the central nervous system.

Dopamine signals mainly through D1 receptors (D1Rs) and D2 receptors (D2Rs); D1R-expressing or D2R-expressing neurons contribute to distinct reward and addictive behaviors. Traditionally, transgenic mice expressing green fluorescent protein (GFP) under D1R or D2R promoters are used for fluorescent verification in electrophysiology studies, whereas Cre mice are employed for behavioral research. However, it is unknown whether the same neuronal populations are targeted in GFP and Cre mice. Additionally, while D1Rs and D2Rs are known to be expressed in different striatal neurons, their expression patterns outside the striatum remain unclear. The present study addressed these two questions by using several transgenic mouse lines expressing fluorescent proteins (GFP or tdTomato) or Cre under the control of D1R or D2R promoters. We found a high degree of overlap between GFP-positive and Cre-positive neurons in the striatum and hippocampus. Additionally, we discovered that D1Rs and D2Rs were highly segregated in the orbitofrontal cortex, prefrontal cortex, dorsal and ventral hippocampus, and amygdala: ~4-34 percent of neurons co-expressed these receptors. Importantly, slice electrophysiological studies demonstrated that D1R-positive and D1R-negative hippocampal neurons were functionally distinct in a mouse line generated by crossing Drd1a-Cre mice with a Cre reporter Ai14 line. Lastly, we discovered that chronic alcohol intake differentially altered D1R-positive and D2R-positive neuron excitability in the ventral CA1. These data suggest that GFP and Cre mice target the same populations of striatal neurons, D1R-expressing or D2R-expressing neurons are highly segregated outside the striatum, and these neurons in the ventral hippocampal may exert distinct roles in alcohol addiction.

Self-Assembled 3D Hierarchical Copper Hydroxyphosphate Modified by the Oxidation of Copper Foil as a Recyclable, Wide Wavelength Photocatalyst.

In this work, three-dimensional flower-like and petal-like copper hydroxyphosphate Cu5(OH)4(PO4)2 (CHP) based on the self-assembly of numerous nanosheets has been successfully fabricated on a copper foil by a mild one-pot wet-chemical method without ligand assistance. This research contributes to the development of the method to change the morphology of the CHP active material by varying the degree of substrate oxidation. The two different CHP architectures were used to photocatalytically degrade rhodamine 6G (Rh 6G) under solar light, which can absorb wide-range light wavelength from the UV to the near-infrared region. They all exhibit high photocatalytic activity and good durability, which are potential candidates for high performance and recyclable wide wavelength photocatalysis.

Alcohol Elicits Functional and Structural Plasticity Selectively in Dopamine D1 Receptor-Expressing Neurons of the Dorsomedial Striatum.

Addiction is thought to be a maladaptive form of learning and memory caused by drug-evoked aberrant synaptic plasticity. We previously showed that alcohol facilitates synaptic plasticity in the dorsomedial striatum (DMS), a brain region that drives goal-directed behaviors. The majority of DMS cells are medium spiny neurons (MSNs) that express dopamine D1 receptors (D1Rs) or D2 receptors (D2Rs), which drive "Go" or "No-Go" behaviors, respectively. Here, we report that alcohol induces cell type-specific synaptic and structural plasticity in the DMS. Using mice that express a fluorescence marker to visualize D1R or D2R MSNs, we show that repeated cycles of systemic administration of alcohol or alcohol consumption induces a long-lasting increase in AMPAR activity specifically in DMS D1R but not in D2R MSNs. Importantly, we report that alcohol consumption increases the complexity of dendritic branching and the density of mature mushroom-shaped spines selectively in DMS D1R MSNs. Finally, we found that blockade of D1R but not D2R activity in the DMS attenuates alcohol consumption. Together, these data suggest that alcohol intake produces profound functional and structural plasticity events in a subpopulation of neurons in the DMS that control reinforcement-related learning. SIGNIFICANCE STATEMENT: Alcohol addiction is considered maladaptive learning and memory processes. Here we unraveled a long-lasting cellular mechanism that may contribute to the memory of alcohol-seeking behaviors. Specifically, we found that alcohol consumption produces a long-lasting enhancement of channel activity and persistent alterations of neuronal morphology in a part of the brain (DMS) that controls alcohol-drinking behaviors. Furthermore, we show that these alterations occur only in a subpopulation of neurons that positively control reward and reinforcement of drugs of abuse. Finally, we report that blocking the activity of this neuronal population reduces alcohol intake. As such synaptic and structural changes are the cellular hallmarks of learning and memory, and these neuroadaptations may drive the development of pathological heavy alcohol consumption.

Chronic Ethanol Exposure Produces Persistent Impairment in Cognitive Flexibility and Decision Signals in the Striatum.

Lack of cognitive flexibility is a hallmark of substance use disorders and has been associated with drug-induced synaptic plasticity in the dorsomedial striatum (DMS). Yet the possible impact of altered plasticity on real-time striatal neural dynamics during decision-making is unclear. Here, we identified persistent impairments induced by chronic ethanol (EtOH) exposure on cognitive flexibility and striatal decision signals. After a substantial withdrawal period from prior EtOH vapor exposure, male, but not female, rats exhibited reduced adaptability and exploratory behavior during a dynamic decision-making task. Reinforcement learning models showed that prior EtOH exposure enhanced learning from rewards over omissions. Notably, neural signals in the DMS related to the decision outcome were enhanced, while those related to choice and choice-outcome conjunction were reduced, in EtOH-treated rats compared to the controls. These findings highlight the profound impact of chronic EtOH exposure on adaptive decision-making, pinpointing specific changes in striatal representations of actions and outcomes as underlying mechanisms for cognitive deficits.