The high relapse rate of drugs is currently a therapeutic dilemma in the treatment of substance use disorder (SUD). Emerging evidence from preclinical animal models demonstrates that pretreatment with selective dopamine D2 receptor (D2R) antagonists prevents reinstatement of drug-seeking. However, the role of D2R downstream signaling in regulating relapse behavior remains unclear. In this study, we investigated the roles of Gαi-protein- and β-arrestin-dependent D2R signaling pathways in cocaine-primed reinstatement using cocaine self-administration (SA) mouse model treated with biased ligands. We found that treatment of D2R Gαi-protein antagonists, but not β-arrestin antagonists, significantly attenuated cocaine-primed reinstatement of drug seeking without affecting locomotor activity or anxiety levels. Administration of D2R Gαi-protein antagonists, but not β-arrestin antagonists, increased cyclic adenosine monophosphate (cAMP) levels in the nucleus accumbens (NAc). Furthermore, treatment of D2R Gαi-protein antagonists, but not β-arrestin antagonists, suppressed cocaine-induced neuronal activation in the NAc. Our results demonstrate that Gαi-protein-dependent D2R signaling plays a crucial role in cocaine-primed reinstatement and suggest that D2R Gαi-protein-biased ligands may be promising pharmacotherapeutic targets for SUD treatment.

The central oxytocin (OXT) system is involved in various aspects of social behavior and emotional regulation. However, the neuronal basis of the functional diversity of paraventricular nucleus (PVN) OXT neurons that modulate the defensive behaviors in response to social threat remains unclear. This study found that acute social defeat stress (ASDS) activates PVN OXT neurons in mice, promoting defensive behaviors during and after ASDS. When the mice were attacked, the nucleus accumbens (NAc)-projecting PVN OXT (OXTPVN-NAc) neurons were inhibited, while the central amygdala (CeA)-projecting PVN OXT (OXTPVN-CeA) neurons were activated. Studies using rabies virus tracing and circuit-specific Oxt knockout revealed that the lateral hypothalamic area (LHA) innervates both OXTPVN-NAc and OXTPVN-CeA neurons, whereas the lateral habenula (LHb) exclusively innervated OXTPVN-CeA neurons. LHA-innervated PVN OXT neurons respond to both social interaction and social defeat (SD). They promote the fight-back behavior during SD and decrease social avoidance after ASDS. In contrast, the LHb-PVNOXT-CeA circuit responded exclusively to SD promoting escape behavior during defeat and increasing the social avoidance after ASDS. Knocking down the OXT receptor (Oxtr) in the NAc decreases fight-back behavior, while knocking down Oxtr in the CeA decreases the escape behavior during defeat and immobility after defeat. These findings clarify that PVN OXT neurons embedded in different circuits promote distinct defensive behaviors in response to social threats and provide insights into the various effects of systematic OXT-based therapies for emotional and social disorders.

Cocaine disrupts the physiological function of the prefrontal cortex and impairs attention, short-term memory, and other cognitive functions. However, the specific cellular basis of maladaptation remains poorly understood. Here, using neuronal activity-dependent tagging, rabies retrograde tracing, electrophysiological recording, and behavioral analyses in mice, we show that a single injection of cocaine increases the recruitment of both the Npas4 transcription-dependent ensemble (N-RAM) and the N-RAM+ somatostatin-expressing interneuron (N-RAM+ SST-IN) ensemble in the medial prefrontal cortex (mPFC). Npas4 induction in mPFC SST-INs upregulates plasticity and excitatory synaptic input from the mediodorsal thalamus (MD). Chemogenetic inhibition of either the N-RAM+ or N-RAM+ SST-IN ensemble in the mPFC impaired attention in the 5‑choice serial reaction time task (5-CSRTT). Our study identifies a unique role of the mPFC N-RAM+ SST-IN ensemble in regulating attention following acute cocaine injection, providing a potential therapeutic target for attention deficits.

Accumulating evidence indicates that drug addiction may lead to adaptive behavioral changes in offspring, potentially due to epigenetic modifications in parental germline. However, the underlying mechanisms remain inadequately understood. In this study, we show that paternal heroin self-administration (SA) increased heroin-seeking behavior in the F1 generation, when compared with offspring sired by yoke-infused control males, indicating cross-generational impact of paternal voluntary heroin seeking behavior. Notably, the increase of heroin seeking behavior in offspring was replicated by zygotic microinjection of sperm RNAs derived from sperm of heroin-SA-experienced rats. Analysis of non-coding RNAs in spermatozoa revealed coordinated changes in miRNA content between the nucleus accumbens and spermatozoa. We validated that restoration of miR-19b downregulation in sperm RNA from self-administration-experienced rats, in parallel with its overexpression in the nucleus accumbens of F1 offspring sired by heroin-SA-experienced fathers, reversed the increased heroin SA observed in these F1 offspring. Taken together, our findings suggest in rats that paternal heroin self-administration induces epigenetic changes in both brain and sperm miRNA, with miR-19b downregulation playing a critical role in mediating the epigenetic inheritance of increased heroin self-administration behavior in the F1 generation.

Engram cells storing episodic memories are allocated to separate neuronal ensembles. However, how these ensembles maintain their stability to drive precise memory expression, and whether their destabilization contributes to aging-related memory deficits, remain elusive. Here, we show that during contextual fear memory consolidation, neuronal pentraxin 1 (NPTX1) in Fos transcription-dependent ensemble (F-RAM) of the dentate gyrus (DG) promotes memory expression in the fear context. NPTX1 facilitates Kv7.2 channel-mediated inhibition of engram cell hyperexcitability, thereby restricting the response of these cells to excitatory inputs from medial entorhinal cortex. Meanwhile, NPTX2 enhances the perisomatic inhibition of Npas4 transcription-dependent ensemble (N-RAM) by parvalbumin+ (PV+) interneurons, thereby preventing fear memory overgeneralization. Pharmacological activation of Kv7.2 channels or chemogenetic activation of PV+ interneurons repaired memory deficits caused by engram-specific NPTX depletion. Contextual fear memory precision and NPTX expression in DG engram cells were decreased in aged mice. Overexpressing NPTX1 in F-RAM ensemble or the AMPAR-binding domain of NPTX2 in N-RAM ensemble rescued contextual fear memory deficits. These findings elucidate that the coordination of NPTX1 and NPTX2 prevents engram ensembles from becoming hyperactive and provide a causal link between engram network destabilization and aging-related contextual fear memory deficits.

Acute stressors, significant risk factors for mood disorders, increase anxiety and reduce reward sensitivity. However, the underlying neuroadaptive mechanisms remain unclear. Here, it is shown that acute restraint stress upregulates Signal Transducer and Activator of Transcription 3 (STAT3) signaling and O-GlcNAcylation in ventral tegmental area (VTA) dopaminergic (DAergic) neurons. Multi-omics analyses in O-linked N-acetylglucosamine transferase (OGT) conditional knockout (cKO) mice reveal a counterbalancing mechanism between O-GlcNAcylation and STAT3Ser727 phosphorylation. In vivo fiber-optic recordings and behavioral experiments demonstrate that STAT3Ser727 phosphorylation mediates the suppression of DAergic neuronal activity and reward sensitivity, as well as the increased anxiety induced by acute restraint stress. Conversely, the upregulation of O-GlcNAcylation in the VTA DAergic neurons prevents these effects. Furthermore, Gabbr2 and Gabrb3 expression is upregulated in the VTA of Ogt cKO mice, whereas the phosphorylation of STAT3Ser727 in the DAergic neurons is required for the upregulation of Gabbr2 and Gabrb3 induced by acute restraint stress. These findings highlight the dynamic and counterbalancing post-translational modifications occurring in the VTA to maintain dopaminergic and emotional homeostasis, offering new insights into neuronal and behavioral responses to acute stress.

The overgeneralization of fear is associated with psychiatric disorders and cognitive decline. Recent studies have shown that engram cells in the dorsal dentate gyrus are integrated into functionally heterogeneous ensembles that are involved in contextual fear memory generalization and discrimination. However, the intracellular signals that promote fear generalization remain to be fully elucidated. In this study, we labeled and manipulated the c-Fos+ and Npas4+ ensembles in the dorsal dentate gyrus that are activated by contextual fear conditioning using a robust activity marking system. The results showed that increasing the excitability of Fos-dependent robust activity marking by overexpressing NaChBac or decreasing the excitability of Npas4-dependent robust activity marking by overexpressing Kir2.1 promoted fear memory generalization. Furthermore, CRISPR-mediated downregulation of the autophagy-related Atg5 or Atg7 genes in dorsal dentate gyrus neurons inhibited activation of c-Fos, but not Npas4. Knockdown of Atg5 or Atg7 in the Fos-dependent robust activity marking or Npas4-dependent robust activity marking ensemble led to an increase in neuronal excitability and a decrease in spine density in both ensembles. However, Atg7 knockdown in the Fos-dependent robust activity marking ensemble promoted memory generalization, while knockdown of Atg5 or Atg7 in the Npas4-dependent robust activity marking ensemble increased anxiety levels. These results contribute to our understanding of how the varying plasticity of memory engrams is involved in regulating fear memory generalization and anxiety.

Engram cells storing specific memories are allocated to separate neuronal ensembles, which preferentially recruit either excitatory or inhibitory inputs to drive precise memory expression. However, how these formed neuronal ensembles maintain their stability, and whether the disturbed stability contributes to aging-related memory deficits remain elusive. Here, we show that neuronal pentraxin1 (NPTX1) facilitates Kv7.2-mediated inhibition of Fos+ ensemble hyperexcitability, thereby restricting its response to excitatory inputs from medial entorhinal cortex (MEC) and promoting memory expression in the fear context. Meanwhile, NPTX2 facilitates the perisomatic inhibition of the Npas4+ ensemble by parvalbumin+ (PV+) interneurons, thus preventing fear memory overgeneralization. Pharmacological activation of Kv7.2 or chemogenetic activation of PV+ interneurons repaired memory deficits caused by engram specific NPTXs depletion. Contextual fear memory precision and NPTXs expression in dentate gyrus (DG) engram cells are decreased in aged mice. Overexpression of NPTX1 in Fos+ ensemble or AMPAR binding domain of NPTX2 in Npas4+ ensemble rescued memory imprecision. These findings elucidate that the coordination of NPTXs prevents engram ensembles from becoming hyperactive and provide a causal link between engram network destabilization and aging-associated memory deficits. ### Competing Interest Statement The authors have declared no competing interest. STI2030-Major Projects, 2021ZD0203500, 2021ZD0202100 Natural Science Foundation of China, 32222033, 31930046, 82021002, 32171041, 31970543, 32270660 CAMS Innovation Fund for Medical Sciences, 2021-I2M-5-009

Peanut productivity is severely restricted by soil salinization and associated nutrient deficiency in saline soil. The quinoa–peanut relay intercrop pattern (IP) is a promising planting system that utilizes the biological advantages of quinoa to improve soil ecological functions and productivity. However, the effects of IP on soil physicochemical and biological properties and the yield formation of the combined peanut crop are still unclear. Two-year field experiments in coastal saline soil were conducted to explore the effects of IP on peanut growth and pod yield, soil physicochemical properties, and microbial community characterization at different growth stages of peanut based on the traditional monocrop pattern (MP). The results show that IP promoted peanut pod yield, although there was the disadvantage of plant growth at an early stage. Soil water content, electrical conductivity (EC), and Na+ content in the peanut rhizosphere were lower, whereas K+, NH4+, and total organic carbon (TOC) contents were higher in IP systems at both the vegetative and reproductive stages. The pod yield of peanut was significantly negatively correlated with soil EC and Na+ contents at the vegetative stage, but positively correlated with K+, NO3−, NH4+, PO43−, and TOC contents at the reproductive stage. IP rebuilt the composition of the soil bacterial community in the peanut rhizosphere and increased the abundance of the beneficial bacterial community, which were positively correlated with soil TOC, K+, NH4+, NO3−, and PO43− contents. These findings suggest that IP can increase peanut pod yield through optimizing soil physicochemical properties and microbial community composition, and it is a promising planting system for improving agricultural production in coastal saline lands.

It has been previously established that paternal development of a strong incentive motivation for cocaine can predispose offspring to develop high cocaine-seeking behavior, as opposed to sole exposure to the drug that results in drug resistance in offspring. However, the adaptive changes of the reward circuitry have not been fully elucidated. To infer the key nuclei and possible hub genes that determine susceptibility to addiction in offspring, rats were randomly assigned to three groups, cocaine self-administration (CSA), yoked administration (Yoke), and saline self-administration (SSA), and used to generate F1. We conducted a comprehensive transcriptomic analysis of the male F1 offspring across seven relevant brain regions, both under drug-naïve conditions and after cocaine self-administration. Pairwise differentially expressed gene analysis revealed that the orbitofrontal cortex (OFC) exhibited more pronounced transcriptomic changes in response to cocaine exposure, while the dorsal hippocampus (dHip), dorsal striatum (dStr), and ventral tegmental area (VTA) exhibited changes that were more closely associated with the paternal voluntary cocaine-seeking behavior. Consistently, these nuclei showed decreased dopamine levels, elevated neuronal activation, and elevated between-nuclei correlations, indicating dopamine-centered rewiring of the midbrain circuit in the CSA offspring. To determine if possible regulatory cascades exist that drive the expression changes, we constructed co-expression networks induced by paternal drug addiction and identified three key clusters, primarily driven by transcriptional factors such as MYT1L, POU3F4, and NEUROD6, leading to changes of genes regulating axonogenesis, synapse organization, and membrane potential, respectively. Collectively, our data highlight vulnerable neurocircuitry and novel regulatory candidates with therapeutic potential for disrupting the transgenerational inheritance of vulnerability to cocaine addiction.

Rac1 is a key regulator of the cytoskeleton and neuronal plasticity, and is known to play a critical role in psychological and cognitive brain disorders. To elucidate the engram specific Rac1 signaling in fear memory, a doxycycline (Dox)-dependent robust activity marking (RAM) system was used to label dorsal dentate gyrus (DG) engram cells in mice during contextual fear conditioning. Rac1 mRNA and protein levels in DG engram cells were peaked at 24 h (day 1) after fear conditioning and were more abundant in the fear engram cells than in the non-engram cells. Optogenetic activation of Rac1 in a temporal manner in DG engram cells before memory retrieval decreased the freezing level in the fear context. Optogenetic activation of Rac1 increased autophagy protein 7 (ATG7) expression in the DG engram cells and activated DG microglia. Microglia-specific transcriptomics and fluorescence in situ hybridization revealed that overexpression of ATG7 in the fear engram cells upregulated the mRNA of Toll-like receptor TLR2/4 in DG microglia. Knockdown of microglial TLR2/4 rescued fear memory destabilization induced by ATG7 overexpression or Rac1 activation in DG engram cells. These results indicate that Rac1-driven communications between engram cells and microglia contributes to contextual fear memory destabilization, and is mediated by ATG7 and TLR2/4, and suggest a novel mechanistic framework for the cytoskeletal regulator in fear memory interference.

Cue-induced cocaine craving gradually intensifies following abstinence, a phenomenon known as the incubation of drug craving. Neuronal ensembles activated by initial cocaine use, are critically involved in this process. However, the mechanisms by which neuronal changes occurring in the ensembles after withdrawal contribute to incubation remain largely unknown. Here we labeled neuronal ensembles in the shell of nucleus accumbens (NAcSh) activated by cocaine conditioned place preference (CPP) training. NAcSh ensembles showed an increasing activity induced by CPP test after 21-day withdrawal. Inhibiting synaptic transmission of NAcSh ensembles suppressed the preference for cocaine paired-side after 21-day withdrawal, demonstrating a critical role of NAcSh ensembles in increased preference for cocaine. The density of dendritic spines in dopamine D1 receptor expressing ensembles was increased after 21-day withdrawal. Moreover, the expression of Grin1, a subunit of the N-methyl-D-aspartate (NMDA) receptor, specifically increased in the NAcSh ensembles after cocaine withdrawal in both CPP and self-administration (SA) mouse models. Targeted knockdown or dysfunction of Grin1 in NAcSh ensembles significantly suppressed craving for cocaine. Our results suggest that the accumulation of NMDA receptors in NAcSh ensembles mediates increased craving for cocaine after prolonged withdrawal, thereby providing potential molecular targets for treatment of drug addiction.

Converging studies demonstrate the dysfunction of the dopaminergic neurons following chronic opioid administration. However, the therapeutic strategies targeting opioid-responsive dopaminergic ensembles that contribute to the development of opioid withdrawal remain to be elucidated. Here, we used the neuronal activity-dependent Tet-Off system to label dopaminergic ensembles in response to initial morphine exposure (Mor-Ens) in the ventral tegmental area (VTA). Fiber optic photometry recording and transcriptome analysis revealed downregulated spontaneous activity and dysregulated mitochondrial respiratory, ultrastructure, and oxidoreductase signal pathways after chronic morphine administration in these dopaminergic ensembles. Mitochondrial fragmentation and the decreased mitochondrial fusion gene mitofusin 1 (Mfn1) were found in these ensembles after prolonged opioid withdrawal. Restoration of Mfn1 in the dopaminergic Mor-Ens attenuated excessive oxidative stress and the development of opioid withdrawal. Administration of Mdivi-1, a mitochondrial fission inhibitor, ameliorated the mitochondrial fragmentation and maladaptation of the neuronal plasticity in these Mor-Ens, accompanied by attenuated development of opioid withdrawal after chronic morphine administration, without affecting the analgesic effect of morphine. These findings highlighted the plastic architecture of mitochondria as a potential therapeutic target for opioid analgesic-induced substance use disorders.

Epidemiological investigations indicate that parental drug abuse experiences significantly influenced the addiction vulnerability of offspring. Studies using animal models have shown that paternal cocaine use and highly motivated drug-seeking behavior are important determinants of offspring addiction susceptibility. However, the key molecules contributing to offspring addiction susceptibility are currently unclear. The motivation for cocaine-seeking behavior in offspring of male rats was compared between those whose fathers self-administered cocaine (SA) and those who were yoked with them and received non-contingent cocaine administrations (Yoke). We found that paternal experience with cocaine-seeking behavior, but not direct cocaine exposure, could lead to increased lever-pressing behavior in male F1 offspring. This effect was observed without significant changes to the dose-response relationship. The transcriptomes of ventral tegmental area (VTA) in offspring were analyzed under both naive state and after self-administration training. Specific transcriptomic changes in response to paternal cocaine-seeking experiences were found, which mainly affected biological processes such as synaptic connections and receptor signaling pathways. Through joint analysis of these candidate genes and parental drug-seeking motivation scores, we found that gamma-aminobutyric acid receptor subunit gamma-3 (Gabrg3) was in the hub position of the drug-seeking motivation-related module network and highly correlated with parental drug-seeking motivation scores. The downregulation of Gabrg3 expression, caused by paternal motivational cocaine-seeking, mainly occurred in GABAergic neurons in the VTA. Furthermore, down-regulating GABAergic Gabrg3 in VTA resulted in an increase in cocaine-seeking behavior in the Yoke F1 group. This down-regulation also reduced transcriptome differences between the Yoke and SA groups, affecting processes related to synaptic formation and neurotransmitter transmission. Taken together, we propose that paternal cocaine-seeking behavior, rather than direct drug exposure, significantly influences offspring addiction susceptibility through the downregulation of Gabrg3 in GABAergic neurons of the VTA, highlighting the importance of understanding specific molecular pathways in the intergenerational inheritance of addiction vulnerability.

The structurally symmetric mammalian brain hemispheres are interconnected by commissural axons across the midline. However, the functions of interhemispheric connectivity remain largely unknown. We found that in mice, transection of the anterior commissure (AC), which connects the rostroventral forebrain, impaired avoidant behaviors. The basolateral amygdala (BLA) in the mouse projects to the contralateral nucleus accumbens (NAc) through the AC, independent of its ipsilateral projections. Aversive stimuli activated contralateral BLA-NAc projections. Positive stimuli, however, activated ipsilateral projections. Selective activation of contralateral BLA-NAc projections activated D2-positive medium spiny neurons (D2-MSNs), reduced NAc dopamine levels, and caused aversion, whereas selective activation of ipsilateral BLA-NAc projections activated D1-MSNs, increased NAc dopamine levels, and induced reward. The contralateral BLA-AC-NAc pathway is crucial for encoding negative valence, demonstrating distinct functions of intra- and interhemispheric circuits in brain physiology.

Background: Neurons in the ventral tegmental area (VTA) are sensitive to stress and their maladaptation have been implicated in the psychiatric disorders such as anxiety and addiction, etc. The cellular properties of the VTA neurons in response to different stressors related to different emotional processing remain to be investigated. Methods: By combining immediate early gene (IEG)-dependent labeling, rabies virus tracing, ensemble-specific transcriptomic analysis and fiber photometry recording in the VTA of male mice, the spatial distribution, brain-wide connectivity and cellular signaling pathways in the VTA neuronal ensembles in response to morphine (Mor-Ens) or foot shock (Shock-Ens) stimuli were investigated. Results: Optogenetic activation of the Mor-Ens drove approach behavior, whereas chemogenetic activation of the Shock-Ens increased the anxiety level in mice. Mor-Ens were clustered and enriched in the ventral VTA, contained a higher proportion of dopaminergic neurons, received more inputs from the dorsal medial striatum and the medial hypothalamic zone, and exhibited greater axonal arborization in the zona incerta and ventral pallidum. Whereas Shock-Ens were more dispersed, contained a higher proportion of GABAergic neurons, and received more inputs from the ventral pallidum and the lateral hypothalamic area. The downstream targets of the G protein and β-arrestin pathways, PLCβ3 and phosphorylated AKT1Thr308, were relatively enriched in the Mor-Ens and Shock-Ens, respectively. Cariprazine, the G-protein-biased agonist for the dopamine D2 receptor, increased the response of Mor-Ens to sucrose water and decreased the anxiety-like behavior during morphine withdrawal, whereas the β-arrestin-biased agonist UNC9994 decreased the response of Shock-Ens to tail suspension. Conclusions: Taken together, these findings reveal the heterogeneous connectivity and signaling pathways of the VTA neurons in response to morphine and foot shock, providing new insights for development of specific interventions for psychiatric disorders caused by various stressors associated with different VTA neuronal functions.

The O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) is a critical post-translational modification that couples the external stimuli to intracellular signal transduction networks. However, the critical protein targets of O-GlcNAcylation in oxidative stress-induced apoptosis remain to be elucidated. Here, we show that treatment with H2O2 inhibited O-GlcNAcylation, impaired cell viability, increased the cleaved caspase 3 and accelerated apoptosis of neuroblastoma N2a cells. The O-GlcNAc transferase (OGT) inhibitor OSMI-1 or the O-GlcNAcase (OGA) inhibitor Thiamet-G enhanced or inhibited H2O2-induced apoptosis, respectively. The total and phosphorylated protein levels, as well as the promoter activities of signal transducer and activator of transcription factor 3 (STAT3) and Forkhead box protein O 1 (FOXO1) were suppressed by OSMI-1. In contrast, overexpressing OGT or treating with Thiamet-G increased the total protein levels of STAT3 and FOXO1. Overexpression of STAT3 or FOXO1 abolished OSMI-1-induced apoptosis. Whereas the anti-apoptotic effect of OGT and Thiamet-G in H2O2-treated cells was abolished by either downregulating the expression or activity of endogenous STAT3 or FOXO1. These results suggest that STAT3 or FOXO1 are the potential targets of O-GlcNAcylation involved in the H2O2-induced apoptosis of N2a cells.

Recent research has indicated that parental use of central nervous system-targeting medications during periconceptional periods may affect offspring across various developmental and behavioral domains. The present study sought to investigate the potential influence of paternal use of donepezil, a specific reversible central acetylcholinesterase inhibitor that activates the cholinergic system to promote cognition, on offspring. In this study, male rats were bred after 21 days of oral donepezil administration at a dose of 4 mg/kg to generate F1 offspring. Both male and female F₁ offspring displayed enhanced performance in learning and short-term memory tests, including novel object recognition, Y maze, and operant learning. Transcriptomic analysis revealed notable alterations in genes associated with the extracellular matrix in the hippocampal tissue of the F1 generation. Integration with genes related to intelligence identified potential core genes that may be involved in the observed behavioral enhancements. These findings indicate that prolonged paternal exposure to donepezil may enhance the learning and memory abilities of offspring, possibly by targeting nonneural, extracellular regions. Further research is required to fully elucidate any potential transgenerational effects.

Soil salinization has become a major environmental factor severely threatening global food security. The application of porous minerals could significantly ameliorate soil fertility and promote plant productivity under salt stress conditions. However, the effects of porous minerals on improving the salt resistance of grain crops in coastal saline soils is not fully studied. In this work, the shoot growth and grain yield of wheat plants grown in coastal saline fields, respectively amended with the four naturally available porous minerals, diatomite, montmorillonite, bentonite and zeolite, were assessed. The application of porous minerals, especially zeolite, significantly improved the biomass and grain yield of wheat plants under saline conditions, as demonstrated by the augmented plant fresh mass (14.8~61.2%) and increased seed size (3.8~58.8%) and number (1.4~57.5%). Soil property analyses exhibited that porous-mineral amendment decreased soil sodium content and sodium absorption ratio, and increased soil nutrients in both the rhizosphere and nonrhizosphere of wheat plants. Further quantitative-PCR and 16S high-throughput sequencing analysis revealed that porous-mineral application also remarkably increased the abundance of bacterial 16S rRNA (0.8~102.4%) and fungal 18S rRNA (89.2~209.6%), and altered the composition of the soil microbial community in the rhizosphere of wheat. Our findings suggest that zeolite could be used as an ideal salt soil amendment, and the changes in soil properties and microorganisms caused by the application of porous minerals like zeolite improved the salt resistance of wheat plants in coastal saline land, leading to increased shoot growth and seed production.