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William Guido - One of the best experts on this subject based on the ideXlab platform.

  • synaptic properties of the feedback connections from the thalamic reticular nucleus to the dorsal lateral geniculate nucleus
    Journal of Neurophysiology, 2020
    Co-Authors: Peter W Campbell, Gubbi Govindaiah, Sean P Masterson, Martha E Bickford, William Guido
    Abstract:

    The thalamic reticular nucleus (TRN) is a shell-like structure comprised of GABAergic neurons that surrounds the dorsal thalamus. While playing a key role in modulating thalamocortical interactions, TRN inhibition of thalamic activity is often thought of as having an all-or-none impact. Although TRN neurons have a dynamic firing range, it remains unclear how variable rates of TRN activity gate thalamocortical transmission. To address this, we examined the ultrastructural features and functional synaptic properties of the feedback connections in the mouse thalamus between TRN and the dorsal lateral geniculate nucleus (dLGN), the principal relay of retinal signals to visual cortex. Using electron microscopy to identify TRN input to dLGN, we found that TRN terminals formed synapses with non-GABAergic postsynaptic profiles. Compared with other nonretinal terminals in dLGN, those from TRN were relatively large and tended to contact proximal regions of relay cell dendrites. To evoke TRN activity in dLGN, we adopted an optogenetic approach by expressing ChR2, or a variant (ChIEF) in TRN terminals. Both in vitro and in vivo recordings revealed that repetitive stimulation of TRN terminals led to a frequency-dependent inhibition of dLGN activity, with higher rates of stimulation resulting in increasing levels of membrane hyperpolarization and corresponding decreases in spike firing. This relationship suggests that alterations in TRN activity lead to graded changes in relay cell spike firing.NEW & NOTEWORTHY The thalamic reticular nucleus (TRN) modulates thalamocortical transmission through inhibition. In mouse, TRN terminals in the dorsal lateral geniculate nucleus (dLGN) form synapses with relay neurons but not interneurons. Stimulation of TRN terminals in dLGN leads to a frequency-dependent form of inhibition, with higher rates of stimulation leading to a greater suppression of spike firing. Thus, TRN inhibition appears more dynamic than previously recognized, having a graded rather than an all-or-none impact on thalamocortical transmission.

  • The absence of retinal input disrupts the development of cholinergic brainstem projections in the mouse dorsal lateral geniculate nucleus
    BMC, 2018
    Co-Authors: Guela Sokhadze, Tania A. Seabrook, William Guido
    Abstract:

    Abstract Background The dorsal lateral geniculate nucleus (dLGN) of the mouse has become a model system for understanding thalamic circuit assembly. While the development of retinal projections to dLGN has been a topic of extensive inquiry, how and when nonretinal projections innervate this nucleus remains largely unexplored. In this study, we examined the development of a major nonretinal projection to dLGN, the ascending input arising from cholinergic neurons of the brainstem. To visualize these projections, we used a transgenic mouse line that expresses red fluorescent protein exclusively in cholinergic neurons. To assess whether retinal input regulates the timing and pattern of cholinergic innervation of dLGN, we utilized the math5-null (math5 −/−) mouse, which lacks retinofugal projections due to a failure of retinal ganglion cell differentiation. Results Cholinergic brainstem innervation of dLGN began at the end of the first postnatal week, increased steadily with age, and reached an adult-like pattern by the end of the first postnatal month. The absence of retinal input led to a disruption in the trajectory, rate, and pattern of cholinergic innervation of dLGN. Anatomical tracing experiments reveal these disruptions were linked to cholinergic projections from parabigeminal nucleus, which normally traverse and reach dLGN through the optic tract. Conclusions The late postnatal arrival of cholinergic projections to dLGN and their regulation by retinal signaling provides additional support for the existence of a conserved developmental plan whereby retinal input regulates the timing and sequencing of nonretinal projections to dLGN

  • organization of the dorsal lateral geniculate nucleus in the mouse
    Visual Neuroscience, 2017
    Co-Authors: Daniel Kerschensteiner, William Guido
    Abstract:

    The dorsal lateral geniculate nucleus (dLGN) of the thalamus is the principal conduit for visual information from retina to visual cortex. Viewed initially as a simple relay, recent studies in the mouse reveal far greater complexity in the way input from the retina is combined, transmitted, and processed in dLGN. Here we consider the structural and functional organization of the mouse retinogeniculate pathway by examining the patterns of retinal projections to dLGN and how they converge onto thalamocortical neurons to shape the flow of visual information to visual cortex.

  • retinal and tectal driver like inputs converge in the shell of the mouse dorsal lateral geniculate nucleus
    The Journal of Neuroscience, 2015
    Co-Authors: Martha E Bickford, Gubbi Govindaiah, Na Zhou, Thomas E Krahe, William Guido
    Abstract:

    The dorsal lateral geniculate nucleus (dLGN) is a model system for understanding thalamic organization and the classification of inputs as “drivers” or “modulators.” Retinogeniculate terminals provide the primary excitatory drive for the relay of information to visual cortex (V1), while nonretinal inputs act in concert to modulate the gain of retinogeniculate signal transmission. How do inputs from the superior colliculus, a visuomotor structure, fit into this schema? Using a variety of anatomical, optogenetic, and in vitro physiological techniques in mice, we show that dLGN inputs from the superior colliculus (tectogeniculate) possess many of the ultrastructural and synaptic properties that define drivers. Tectogeniculate and retinogeniculate terminals converge to innervate one class of dLGN neurons within the dorsolateral shell, the primary terminal domain of direction-selective retinal ganglion cells. These dLGN neurons project to layer I of V1 to form synaptic contacts with dendrites of deeper-layer neurons. We suggest that tectogeniculate inputs act as “backseat drivers,” which may alert shell neurons to movement commands generated by the superior colliculus. SIGNIFICANCE STATEMENT The conventional view of the dorsal lateral geniculate nucleus (dLGN) is that of a simple relay of visual information between the retina and cortex. Here we show that the dLGN receives strong excitatory input from both the retina and the superior colliculus. Thus, the dLGN is part of a specialized visual channel that provides cortex with convergent information about stimulus motion and eye movement and positioning.

Liefen Shyur - One of the best experts on this subject based on the ideXlab platform.

  • plant galactolipid dlgg suppresses lung metastasis of melanoma through deregulating tnf α mediated pulmonary vascular permeability and circulating oxylipin dynamics in mice
    International Journal of Cancer, 2018
    Co-Authors: Chungchih Yang, Mengting Chang, Cheng Kuei Chang, Liefen Shyur
    Abstract:

    This study demonstrates the bioefficacy and gives mechanistic insights into a plant galactolipid 1,2-di-O-linolenoyl-3-O-β-galactopyranosyl-sn-glycerol (dLGG) against metastatic melanoma using a syngeneic mouse model implanted with B16COX-2/Luc melanoma. dLGG-20 (p.o. dLGG 20 mg/kg) and anti-cancer drug CP-2 (i.p. cisplatin 2 mg/kg) treatment significantly inhibited lung metastasis of melanoma in mice 91 and 57%, respectively, as determined by bioluminescence intensity. Moreover, dLGG-20 and CP-2 treatment prolonged mouse mean survival time. dLGG-20 treatment significantly inhibited the expression levels of several molecular markers, that is, PCNA, MMP2, COX-2, VEGF, vimentin, snail, TGF-β, β-catenin, TNF-α, PD-1 and PD-L1 in mouse lung tissues compared to tumor control mice. Significant inhibition of macrophage and neutrophil infiltration and promotion of CD8 + Tc cell recruitment in the lung microenvironment was observed in dLGG-20-treated mice. A LC/MS-based comparative oxylipin metabolomics study showed that dLGG-20 treatment significantly induced (5.0- to 12.8-fold) the 12/15-LOX catalyzed oxylipin products in mouse serum including 17-HDHA from DHA, 15-HEPE from EPA, 8- and 12-HETEs from AA, and CYP450-derived 20-HETE from AA. CP-2 treatment increased 12/15-LOX derived 8-, 11- and 12-HETEs from AA, and CYP450 derived 11,12-EET from AA ad 9,10-DHOME from LA by 5.3- to 8.1-fold. Of note, dLGG and 17-HDHA were more effective than CP in preventing B16 melanoma cell-induced pulmonary vascular permeability in mice through inhibition of TNF-α production, up-regulation of tight junction proteins claudin1 and ZO-2 and deregulation of Src activation. In conclusion, this study shows the novel therapeutic effect of phytoagent dLGG and suggests its potential as a therapeutic agent for metastatic melanoma.

  • abstract a111 plant galactolipid dlgg suppresses lung metastasis of melanoma through modulating endothelial mesenchymal transition extravasation and oxylipins dynamics
    Molecular Cancer Therapeutics, 2015
    Co-Authors: Chungchih Yang, Mengting Chang, Liefen Shyur
    Abstract:

    A galactolipid 1,2-di-O-linolenoyl-3-O-s-galactopyranosyl-sn-glycerol (designated dLGG) isolated from medicinal plant Crassocephalum rabens (Asteraceae) was demonstrated to be anti-inflammatory and anti-melanoma tumor growth in syngeneic mouse system in our laboratory. In this study, an experimental lung metastasis mouse model using a B16 melanoma cell clone (designated B16COX-2/Luc) carrying COX-2 promoter driven luciferase reporter gene was established to monitor the cancer cell growth and metastasis in animals and the dLGG effect. Our data showed that dLGG (20 mg/kg BW, dLGG−20), cisplatin (2 mg/kg BW, CP−2), and combination drug treatment (CP−2+dLGG−20) significantly inhibited lung metastasis of melanoma in mice from 100% at tumor control group to 9.2%, 43.1%, and 4.1%, respectively, as determined by bioluminescence intensity. The dLGG (30±8 days), cisplatin (35±9 days) and combination treatment group (29±7 days) mice showed longer mean survival time than tumor control group (22±1 days)(P Citation Format: Chung-Chih Yang, Meng-Ting Chang, Lie-Fen Shyur. Plant galactolipid dLGG suppresses lung metastasis of melanoma through modulating endothelial-mesenchymal transition extravasation and oxylipins dynamics. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A111.

  • a galactolipid possesses novel cancer chemopreventive effects by suppressing inflammatory mediators and mouse b16 melanoma
    Cancer Research, 2007
    Co-Authors: Chia Chung Hou, Yi Ping Chen, Chi Chang Huang, Shengyang Wang, Ningsun Yang, Liefen Shyur
    Abstract:

    Crassocephalum rabens (Asteraceae) is a popular anti-inflammatory folk medicine and food supplement. We investigated the cancer chemopreventive bioactivity of C. rabens phytocompounds in vitro and in vivo using cell- and gene-based bioassays and a mouse B16 melanoma model. The bioactive glyceroglycolipid 1,2-di-O-alpha-linolenoyl-3-O-beta-galactopyranosyl-sn-glycerol (dLGG) that was identified from C. rabens was found in vitro and in vivo to be a potent nitric oxide (NO) scavenger. dLGG treatment inhibited both mRNA and protein expression of inducible NO synthase and cyclooxygenase-2 (COX-2) in murine macrophages and inhibited COX-2 gene transcription in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated B16 cells. In immunohistochemical studies, dLGG inhibited TPA-induced expression of COX-2 and nitration of proteins in mouse skin. dLGG could also significantly inhibit lipopolysaccharide-induced prostaglandin E(2) production in murine macrophages. Furthermore, dLGG prevented nuclear translocation of cytoplasmic nuclear factor-kappaB (NF-kappaB) by suppressing IkappaBalpha phosphorylation and degradation. Structure-activity relationship study by electrophoretic mobility shift assay indicated that the dilinolenoylglycerol moiety in dLGG is the essential structural feature preventing NF-kappaB.DNA complex formation. A dLGG-enriched extract from C. rabens (10 mg/kg) markedly suppressed B16 melanoma growth in C57BL/6J mice following i.p. administration, an effect comparable with that of cisplatin, a cancer chemotherapeutic drug. This study shows the detailed molecular mechanism(s) underlying the anti-inflammatory and tumor-suppressive effects of a natural galactolipid.

Daniela Gardiol - One of the best experts on this subject based on the ideXlab platform.

  • differential expression of dlg1 as a common trait in different human diseases an encouraging issue in molecular pathology
    Biological Chemistry, 2019
    Co-Authors: Federico Marziali, Maria Paula Dizanzo, Ana Laura Cavatorta, Daniela Gardiol
    Abstract:

    Human disc large (DLG1) is a scaffolding protein that through the interaction with diverse cell partners participates in the control of key cellular processes such as polarity, proliferation and migration. Experimental data have mainly identified DLG1 as a tumor suppressor. An outstanding point for DLG1 protein is that altered DLG1 expression and DLG1 gene mutations were observed in different pathologies, including cancer and neurological and immunological disorders. Evident changes in DLG1 abundance and/or cell localization were identified in a number of studies suggesting its participation in molecular mechanisms responsible for the development of such illnesses. In this review, we focus on some of the latest findings regarding DLG1 alterations in different diseases as well as its potential use as a biomarker for pathological progression. We further address the current knowledge on the molecular mechanisms regulating DLG1 expression and the posttranslational modifications that may affect DLG1 cell localization and functions. Despite the advances in this field, there are still open questions about the precise molecular link between alterations in DLG1 expression and the development of each specific pathology. The complete understanding of this concern will give us new scenarios for the design of promising diagnosis and therapeutic tools.

  • dlg1 polarity protein expression associates with the disease progress of low grade cervical intraepithelial lesions
    Experimental and Molecular Pathology, 2017
    Co-Authors: Ana Laura Cavatorta, Federico Marziali, Alejandra Di Gregorio, Marina Paula Bugnon Valdano, Mariela Cabral, Hebe Bottai, Jorge Cittadini, Ana Lia Nocito, Daniela Gardiol
    Abstract:

    Human Disc large tumor suppressor (DLG1) participates in regulating cell polarity and proliferation, suggesting an important connection between epithelial organization and cellular growth control. However, it was demonstrated that DLG1 could acquire oncogenic attributes in some specific contexts. In this work, we evaluated the expression of DLG1 and its contribution to the progress of cervical lesions in order to investigate a potential role of this polarity protein in human oncogenic processes. We analyzed cervical biopsies from women with low-grade squamous intraepithelial lesion (LSIL) diagnosis (n=30), for DLG1 expression by immunohistochemistry. These results were correlated with the clinical monitoring of the patients during a 24-month follow-up period. Our data indicate that while all LSIL patients with a DLG1 staining pattern similar to normal tissues are significantly more likely to regress (n=23, Pattern I), all LSIL biopsy specimens showing a diffuse and intense DLG1 staining likely progress to high-grade lesions (n=4, Pattern II). Finally, all persistent LSIL analyzed showed an undetermined DLG1 staining, with a diffuse distribution without a strong intensity (n=3, Pattern III). We found a significant association between the expression pattern of DLG1 and the evolution of the lesion (p<0.00001). This work contributes to the knowledge of DLG1 biological functions, suggesting that its expression may have an important role in the progression of early dysplastic cervical lesions, giving prognostic information.

  • regulation of translational efficiency by different splice variants of the disc large 1 oncosuppressor 5 utr
    FEBS Journal, 2011
    Co-Authors: Ana Laura Cavatorta, Federico Marziali, Marina Paula Bugnon Valdano, Florencia Natalia Facciuto, Adriana A Giri, Lawrence Banks, Daniela Gardiol
    Abstract:

    Human Disc large (DLG1) has been demonstrated to be involved in the control of cell polarity and maintenance of tissue architecture, and is frequently lost in human tumours. However, the mechanisms controlling DLG1 expression are poorly understood. To further examine the regulation of DLG1 expression, we analysed the 5' ends of DLG1 transcripts by rapid amplification of cDNA ends polymerase chain reaction. We identified an alternative splicing event in the 5' region of DLG1 mRNA that generates transcripts with two different 5' untranslated regions (5'-UTRs). We show by reporter assays that the DLG1 5'-UTR containing an alternatively spliced exon interferes with the translation of a downstream open reading frame (ORF). However, no significant differences in mRNA stability among the DLG1 5'-UTR variants were observed. Sequence analysis of the additional exon present in the larger DLG1 5'-UTR showed the presence of an upstream short ORF which is lost in the short version of the 5'-UTR DLG1. By mutagenesis and luciferase assays, we analysed the contribution of this upstream short ORF in reducing translation efficiency, and showed that its disruption can revert, to some extent, the negative regulation of large 5'-UTR. Using computational modelling we also show that the large DLG1 5'-UTR isoform forms a more stable structure than the short version, and this may contribute to its ability to repress translation. This represents the first analysis of the 5' region of the DLG1 transcripts and shows that differential expression of alternatively spliced 5'-UTRs with different translational properties could result in changes in DLG1 abundance.

Chungchih Yang - One of the best experts on this subject based on the ideXlab platform.

  • plant galactolipid dlgg suppresses lung metastasis of melanoma through deregulating tnf α mediated pulmonary vascular permeability and circulating oxylipin dynamics in mice
    International Journal of Cancer, 2018
    Co-Authors: Chungchih Yang, Mengting Chang, Cheng Kuei Chang, Liefen Shyur
    Abstract:

    This study demonstrates the bioefficacy and gives mechanistic insights into a plant galactolipid 1,2-di-O-linolenoyl-3-O-β-galactopyranosyl-sn-glycerol (dLGG) against metastatic melanoma using a syngeneic mouse model implanted with B16COX-2/Luc melanoma. dLGG-20 (p.o. dLGG 20 mg/kg) and anti-cancer drug CP-2 (i.p. cisplatin 2 mg/kg) treatment significantly inhibited lung metastasis of melanoma in mice 91 and 57%, respectively, as determined by bioluminescence intensity. Moreover, dLGG-20 and CP-2 treatment prolonged mouse mean survival time. dLGG-20 treatment significantly inhibited the expression levels of several molecular markers, that is, PCNA, MMP2, COX-2, VEGF, vimentin, snail, TGF-β, β-catenin, TNF-α, PD-1 and PD-L1 in mouse lung tissues compared to tumor control mice. Significant inhibition of macrophage and neutrophil infiltration and promotion of CD8 + Tc cell recruitment in the lung microenvironment was observed in dLGG-20-treated mice. A LC/MS-based comparative oxylipin metabolomics study showed that dLGG-20 treatment significantly induced (5.0- to 12.8-fold) the 12/15-LOX catalyzed oxylipin products in mouse serum including 17-HDHA from DHA, 15-HEPE from EPA, 8- and 12-HETEs from AA, and CYP450-derived 20-HETE from AA. CP-2 treatment increased 12/15-LOX derived 8-, 11- and 12-HETEs from AA, and CYP450 derived 11,12-EET from AA ad 9,10-DHOME from LA by 5.3- to 8.1-fold. Of note, dLGG and 17-HDHA were more effective than CP in preventing B16 melanoma cell-induced pulmonary vascular permeability in mice through inhibition of TNF-α production, up-regulation of tight junction proteins claudin1 and ZO-2 and deregulation of Src activation. In conclusion, this study shows the novel therapeutic effect of phytoagent dLGG and suggests its potential as a therapeutic agent for metastatic melanoma.

  • abstract a111 plant galactolipid dlgg suppresses lung metastasis of melanoma through modulating endothelial mesenchymal transition extravasation and oxylipins dynamics
    Molecular Cancer Therapeutics, 2015
    Co-Authors: Chungchih Yang, Mengting Chang, Liefen Shyur
    Abstract:

    A galactolipid 1,2-di-O-linolenoyl-3-O-s-galactopyranosyl-sn-glycerol (designated dLGG) isolated from medicinal plant Crassocephalum rabens (Asteraceae) was demonstrated to be anti-inflammatory and anti-melanoma tumor growth in syngeneic mouse system in our laboratory. In this study, an experimental lung metastasis mouse model using a B16 melanoma cell clone (designated B16COX-2/Luc) carrying COX-2 promoter driven luciferase reporter gene was established to monitor the cancer cell growth and metastasis in animals and the dLGG effect. Our data showed that dLGG (20 mg/kg BW, dLGG−20), cisplatin (2 mg/kg BW, CP−2), and combination drug treatment (CP−2+dLGG−20) significantly inhibited lung metastasis of melanoma in mice from 100% at tumor control group to 9.2%, 43.1%, and 4.1%, respectively, as determined by bioluminescence intensity. The dLGG (30±8 days), cisplatin (35±9 days) and combination treatment group (29±7 days) mice showed longer mean survival time than tumor control group (22±1 days)(P Citation Format: Chung-Chih Yang, Meng-Ting Chang, Lie-Fen Shyur. Plant galactolipid dLGG suppresses lung metastasis of melanoma through modulating endothelial-mesenchymal transition extravasation and oxylipins dynamics. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A111.

Soo Young Kim - One of the best experts on this subject based on the ideXlab platform.

  • Taesun Yoo,1 Sun-Gyun Kim,2 Soo Hyun Yang,3 Hyun Kim,3 Eunjoon Kim,1,2 and Soo Young Kimcorresponding author4
    BMC, 2020
    Co-Authors: Taesun Yoo, Sun-gyun Kim, Soo Hyun Yang, Hyun Kim, Eunjoon Kim, Soo Young Kim
    Abstract:

    Background DLG2, also known as postsynaptic density protein-93 (PSD-93) or chapsyn-110, is an excitatory postsynaptic scaffolding protein that interacts with synaptic surface receptors and signaling molecules. A recent study has demonstrated that mutations in the DLG2 promoter region are significantly associated with autism spectrum disorder (ASD). Although DLG2 is well known as a schizophrenia-susceptibility gene, the mechanisms that link DLG2 gene disruption with ASD-like behaviors remain unclear. Methods Mice lacking exon 14 of the Dlg2 gene (Dlg2(-/-) mice) were used to investigate whether Dlg2 deletion leads to ASD-like behavioral abnormalities. To this end, we performed a battery of behavioral tests assessing locomotion, anxiety, sociability, and repetitive behaviors. In situ hybridization was performed to determine expression levels of Dlg2 mRNA in different mouse brain regions during embryonic and postnatal brain development. We also measured excitatory and inhibitory synaptic currents to determine the impacts of Dlg2 deletion on synaptic transmission in the dorsolateral striatum. Results Dlg2(-/-) mice showed hypoactivity in a novel environment. They also exhibited decreased social approach, but normal social novelty recognition, compared with wild-type animals. In addition, Dlg2(-/-) mice displayed strong self-grooming, both in home cages and novel environments. Dlg2 mRNA levels in the striatum were heightened until postnatal day 7 in mice, implying potential roles of DLG2 in the development of striatal connectivity. In addition, the frequency of excitatory, but not inhibitory, spontaneous postsynaptic currents in the Dlg2(-/-) dorsolateral striatum was significantly reduced. Conclusion These results suggest that homozygous Dlg2 deletion in mice leads to ASD-like behavioral phenotypes, including social deficits and increased repetitive behaviors, as well as reductions in excitatory synaptic input onto dorsolateral spiny projection neurons, implying that the dorsal striatum is one of the brain regions vulnerable to the developmental dysregulation of DLG2. C. The Author(s) 202

  • Taesun Yoo,1 Sun-Gyun Kim,2 Soo Hyun Yang,3 Hyun Kim,3 Eunjoon Kim,1,2 and Soo Young Kimcorresponding author4
    'Springer Science and Business Media LLC', 2020
    Co-Authors: Taesun Yoo, Sun-gyun Kim, Soo Hyun Yang, Hyun Kim, Eunjoon Kim, Soo Young Kim
    Abstract:

    Background DLG2, also known as postsynaptic density protein-93 (PSD-93) or chapsyn-110, is an excitatory postsynaptic scaffolding protein that interacts with synaptic surface receptors and signaling molecules. A recent study has demonstrated that mutations in the DLG2 promoter region are significantly associated with autism spectrum disorder (ASD). Although DLG2 is well known as a schizophrenia-susceptibility gene, the mechanisms that link DLG2 gene disruption with ASD-like behaviors remain unclear. Methods Mice lacking exon 14 of the Dlg2 gene (Dlg2(-/-) mice) were used to investigate whether Dlg2 deletion leads to ASD-like behavioral abnormalities. To this end, we performed a battery of behavioral tests assessing locomotion, anxiety, sociability, and repetitive behaviors. In situ hybridization was performed to determine expression levels of Dlg2 mRNA in different mouse brain regions during embryonic and postnatal brain development. We also measured excitatory and inhibitory synaptic currents to determine the impacts of Dlg2 deletion on synaptic transmission in the dorsolateral striatum. Results Dlg2(-/-) mice showed hypoactivity in a novel environment. They also exhibited decreased social approach, but normal social novelty recognition, compared with wild-type animals. In addition, Dlg2(-/-) mice displayed strong self-grooming, both in home cages and novel environments. Dlg2 mRNA levels in the striatum were heightened until postnatal day 7 in mice, implying potential roles of DLG2 in the development of striatal connectivity. In addition, the frequency of excitatory, but not inhibitory, spontaneous postsynaptic currents in the Dlg2(-/-) dorsolateral striatum was significantly reduced. Conclusion These results suggest that homozygous Dlg2 deletion in mice leads to ASD-like behavioral phenotypes, including social deficits and increased repetitive behaviors, as well as reductions in excitatory synaptic input onto dorsolateral spiny projection neurons, implying that the dorsal striatum is one of the brain regions vulnerable to the developmental dysregulation of DLG2. C. The Author(s) 202011Nsciescopu