{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T07:52:15Z","timestamp":1782892335607,"version":"3.54.5"},"reference-count":82,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a negative regulator of the mTOR pathway and is strongly associated with autism spectrum disorder (ASD), with up to 25% of ASD patients with macrocephaly harboring PTEN mutations. Mice with germline PTEN haploinsufficiency show behavioral characteristics resembling ASD, as do various mouse models with conditional knockouts of PTEN. Human tissue studies and those from multiple genetic mouse models suggest that dysfunction of GABAergic interneurons may play a role in the development of ASD, but the precise mechanisms remain elusive. PTEN provides a target for investigation because it regulates the development of inhibitory neurons arising from the medial ganglionic eminence, promoting the survival and maturation of parvalbumin (PV+) neurons at the expense of somatostatin (SOM+) neurons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we investigate how PTEN regulates SOM+ neurons at the cellular and circuit level in the central lateral amygdala (CeL), an area that governs the key ASD behavioral symptoms of social anxiety and altered emotional motivation for social engagement using behavioral analysis, electrophysiology, and two-photon local circuit mapping.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that knocking out PTEN in SOM+ neurons results in elevated levels of fear and anxiety and decreases CeL local circuit connectivity. Specifically, this manipulation decreased the strength of connections between individual neurons and altered the distribution of local connections in a cell-type specific manner. In contrast to the deficit in local inhibitory connections within CeL, the excitatory drive from the major CeL input, the basolateral amygdala (BLA) was enhanced.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This combined imbalance of enhanced excitation and diminished local inhibition likely underlies the heightened fear learning and anxiety we observed in the PTEN-SOM-KO mice.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fncel.2025.1597131","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T05:29:52Z","timestamp":1750915792000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["PTEN in somatostatin neurons regulates fear and anxiety and is required for inhibitory synaptic connectivity within central amygdala"],"prefix":"10.3389","volume":"19","author":[{"given":"Timothy W.","family":"Holford","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn N.","family":"Letourneau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Von-Walter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Moncaleano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cody L.","family":"Loomis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. McLean","family":"Bolton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5567","DOI":"10.1523\/JNEUROSCI.0705-18.2018","article-title":"A central extended amygdala circuit that modulates anxiety.","volume":"38","author":"Ahrens","year":"2018","journal-title":"J Neurosci"},{"key":"B2","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/j.neuron.2020.10.031","article-title":"Mediodorsal and ventromedial thalamus engage distinct L1 circuits in the prefrontal cortex.","volume":"109","author":"Anastasiades","year":"2021","journal-title":"Neuron"},{"key":"B3","doi-asserted-by":"publisher","first-page":"5253","DOI":"10.1242\/jcs.156554","article-title":"PTEN counteracts PIP3 upregulation in spines during NMDA-receptor-dependent long-term depression.","volume":"127","author":"Arendt","year":"2014","journal-title":"J. Cell Sci"},{"key":"B4","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1038\/nn.2462","article-title":"PIP3 controls synaptic function by maintaining AMPA receptor clustering at the postsynaptic membrane.","volume":"13","author":"Arendt","year":"2010","journal-title":"Nat. Neurosci"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1212\/wnl.57.7.1269","article-title":"Autism in tuberous sclerosis complex is related to both cortical and subcortical dysfunction.","volume":"57","author":"Asano","year":"2001","journal-title":"Neurology"},{"key":"B6","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1038\/ng782","article-title":"Deletion of Pten in mouse brain causes seizures, ataxia and defects in soma size resembling Lhermitte-Duclos disease.","volume":"29","author":"Backman","year":"2001","journal-title":"Nat. Genet"},{"key":"B7","doi-asserted-by":"publisher","first-page":"e14193","DOI":"10.7554\/eLife.14193","article-title":"Cellular resolution circuit mapping with temporal-focused excitation of soma-targeted channelrhodopsin.","volume":"5","author":"Baker","year":"2016","journal-title":"Elife"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.3389\/fpsyt.2019.01016","article-title":"Sensory abnormalities in autism spectrum disorders: A focus on the tactile domain, from genetic mouse models to the clinic.","volume":"10","author":"Balasco","year":"2020","journal-title":"Front. Psychiatry"},{"key":"B9","doi-asserted-by":"publisher","first-page":"12829","DOI":"10.1038\/ncomms12829","article-title":"Pten and EphB4 regulate the establishment of perisomatic inhibition in mouse visual cortex.","volume":"7","author":"Baohan","year":"2016","journal-title":"Nat. Commun"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.1152\/jn.90635.2008","article-title":"Differential activity-dependent, homeostatic plasticity of two neocortical inhibitory circuits.","volume":"100","author":"Bartley","year":"2008","journal-title":"J. Neurophysiol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1136\/jmg.2004.024646","article-title":"Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations.","volume":"42","author":"Butler","year":"2005","journal-title":"J. Med. Genet"},{"key":"B12","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.biopsych.2019.11.003","article-title":"Making sense of antisense: Getting from a locus to a gene.","volume":"87","author":"Buxbaum","year":"2020","journal-title":"Biol. Psychiatry"},{"key":"B13","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1002\/ajmg.b.30493","article-title":"Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly.","author":"Buxbaum","year":"2007","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet"},{"key":"B14","doi-asserted-by":"publisher","first-page":"10252","DOI":"10.1523\/JNEUROSCI.5272-14.2015","article-title":"Pten mutations alter brain growth trajectory and allocation of cell types through elevated \u03b2-Catenin signaling.","volume":"35","author":"Chen","year":"2015","journal-title":"J. Neurosci"},{"key":"B15","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1038\/nature09559","article-title":"Encoding of conditioned fear in central amygdala inhibitory circuits.","volume":"468","author":"Ciocchi","year":"2010","journal-title":"Nature"},{"key":"B16","doi-asserted-by":"publisher","first-page":"3490","DOI":"10.1093\/hmg\/ddu057","article-title":"Pten haploinsufficient mice show broad brain overgrowth but selective impairments in autism-relevant behavioral tests.","volume":"23","author":"Clipperton-Allen","year":"2014","journal-title":"Hum. Mol. Genet"},{"key":"B17","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1111\/gbb.12192","article-title":"Decreased aggression and increased repetitive behavior in Pten haploinsufficient mice.","volume":"14","author":"Clipperton-Allen","year":"2015","journal-title":"Genes Brain Behav"},{"key":"B18","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1007\/s10571-024-01529-7","article-title":"AMPA receptors in synaptic plasticity, memory function, and brain diseases.","volume":"45","author":"de Le\u00f3n-L\u00f3pez","year":"2025","journal-title":"Cell Mol. Neurobiol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/nature13772","article-title":"Synaptic, transcriptional and chromatin genes disrupted in autism.","volume":"515","author":"De Rubeis","year":"2014","journal-title":"Nature"},{"key":"B20","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1007\/s00787-005-0443-1","article-title":"Consensus clinical guidelines for the assessment of cognitive and behavioural problems in Tuberous Sclerosis.","volume":"14","author":"de Vries","year":"2005","journal-title":"Eur. Child Adolesc. Psychiatry"},{"key":"B21","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1038\/1235","article-title":"Pten is essential for embryonic development and tumour suppression.","volume":"19","author":"Di Cristofano","year":"1998","journal-title":"Nat. Genet"},{"key":"B22","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1038\/nature21047","article-title":"A competitive inhibitory circuit for selection of active and passive fear responses.","volume":"542","author":"Fadok","year":"2017","journal-title":"Nature"},{"key":"B23","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.conb.2018.02.009","article-title":"New perspectives on central amygdala function.","volume":"49","author":"Fadok","year":"2018","journal-title":"Curr. Opin. Neurobiol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"327","DOI":"10.3389\/fncel.2014.00327","article-title":"Shaping inhibition: Activity dependent structural plasticity of GABAergic synapses.","volume":"8","author":"Flores","year":"2014","journal-title":"Front. Cell Neurosci"},{"key":"B25","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1016\/j.neuroscience.2007.10.048","article-title":"Phosphatase and tensin homolog, deleted on chromosome 10 deficiency in brain causes defects in synaptic structure, transmission and plasticity, and myelination abnormalities.","volume":"151","author":"Fraser","year":"2008","journal-title":"Neuroscience"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1038\/mp.2014.125","article-title":"Molecular and phenotypic abnormalities in individuals with germline heterozygous PTEN mutations and autism.","volume":"20","author":"Frazier","year":"2015","journal-title":"Mol. Psychiatry"},{"key":"B27","doi-asserted-by":"publisher","first-page":"18297","DOI":"10.1073\/pnas.1309207110","article-title":"Overexpression of calcium-activated potassium channels underlies cortical dysfunction in a model of PTEN-associated autism.","volume":"110","author":"Garcia-Junco-Clemente","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"B28","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1186\/s12943-023-01827-6","article-title":"PI3K\/AKT\/mTOR signaling transduction pathway and targeted therapies in cancer.","volume":"22","author":"Glaviano","year":"2023","journal-title":"Mol. Cancer"},{"key":"B29","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1073\/pnas.0509939103","article-title":"PTEN negatively regulates neural stem cell self-renewal by modulating G0-G1 cell cycle entry.","volume":"103","author":"Groszer","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"B30","doi-asserted-by":"publisher","first-page":"2000","DOI":"10.1038\/s41593-019-0528-7","article-title":"Dynamic remodeling of a basolateral-to-central amygdala glutamatergic circuit across fear states.","volume":"22","author":"Hartley","year":"2019","journal-title":"Nat. Neurosci"},{"key":"B31","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1038\/nn1677","article-title":"Activity-dependent regulation of inhibitory synaptic transmission in hippocampal neurons.","volume":"9","author":"Hartman","year":"2006","journal-title":"Nat. Neurosci"},{"key":"B32","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/nature09553","article-title":"Genetic dissection of an amygdala microcircuit that gates conditioned fear.","volume":"468","author":"Haubensak","year":"2010","journal-title":"Nature"},{"key":"B33","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1038\/ejhg.2013.114","article-title":"Biochemical screening and PTEN mutation analysis in individuals with autism spectrum disorders and macrocephaly.","volume":"22","author":"Hobert","year":"2014","journal-title":"Eur. J. Hum. Genet"},{"key":"B34","doi-asserted-by":"publisher","first-page":"13421","DOI":"10.1038\/ncomms13421","article-title":"Hyperconnectivity of prefrontal cortex to amygdala projections in a mouse model of macrocephaly\/autism syndrome.","volume":"7","author":"Huang","year":"2016","journal-title":"Nat. Commun"},{"key":"B35","doi-asserted-by":"publisher","first-page":"ENEURO.0367-16.2017","DOI":"10.1523\/ENEURO.0367-16.2017","article-title":"Intrinsic circuits in the lateral central amygdala.","volume":"4","author":"Hunt","year":"2017","journal-title":"eNeuro"},{"key":"B36","doi-asserted-by":"publisher","first-page":"7966","DOI":"10.1523\/JNEUROSCI.1054-09.2009","article-title":"GABA-cAMP response element-binding protein signaling regulates maturation and survival of newly generated neurons in the adult hippocampus.","volume":"29","author":"Jagasia","year":"2009","journal-title":"J. Neurosci"},{"key":"B37","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1038\/nature14188","article-title":"From circuits to behaviour in the amygdala.","volume":"517","author":"Janak","year":"2015","journal-title":"Nature"},{"key":"B38","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.neuron.2013.03.016","article-title":"Modeling autism by SHANK gene mutations in mice.","volume":"78","author":"Jiang","year":"2013","journal-title":"Neuron"},{"key":"B39","doi-asserted-by":"publisher","first-page":"8691","DOI":"10.1523\/JNEUROSCI.2478-06.2006","article-title":"Major effects of sensory experiences on the neocortical inhibitory circuits.","volume":"26","author":"Jiao","year":"2006","journal-title":"J. Neurosci"},{"key":"B40","doi-asserted-by":"publisher","first-page":"2827","DOI":"10.1038\/emboj.2010.160","article-title":"PTEN is recruited to the postsynaptic terminal for NMDA receptor-dependent long-term depression.","volume":"29","author":"Jurado","year":"2010","journal-title":"EMBO J"},{"key":"B41","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1038\/s41592-025-02610-9","article-title":"Genetically encoded biosensor for fluorescence lifetime imaging of PTEN dynamics in the intact brain.","volume":"22","author":"Kagan","year":"2025","journal-title":"Nat. Methods"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41398-023-02374-w","article-title":"Comorbidities in autism spectrum disorder and their etiologies.","volume":"13","author":"Khachadourian","year":"2023","journal-title":"Transl. Psychiatry"},{"key":"B43","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1002\/aur.1266","article-title":"Macrocephaly as a clinical indicator of genetic subtypes in autism.","volume":"6","author":"Klein","year":"2013","journal-title":"Autism Res"},{"key":"B44","doi-asserted-by":"publisher","first-page":"12281","DOI":"10.1523\/JNEUROSCI.0688-10.2010","article-title":"Atypical reflexive gaze patterns on emotional faces in autism spectrum disorders.","volume":"30","author":"Kliemann","year":"2010","journal-title":"J. Neurosci"},{"key":"B45","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.neuron.2006.03.023","article-title":"Pten regulates neuronal arborization and social interaction in mice.","volume":"50","author":"Kwon","year":"2006","journal-title":"Neuron"},{"key":"B46","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1016\/j.biopsych.2016.05.011","article-title":"Excitation\/inhibition imbalance in animal models of autism spectrum disorders.","volume":"81","author":"Lee","year":"2017","journal-title":"Biol. Psychiatry"},{"key":"B47","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.cobeha.2018.09.012","article-title":"Central amygdala cells for learning and expressing aversive emotional memories.","volume":"26","author":"Li","year":"2019","journal-title":"Curr. Opin. Behav. Sci"},{"key":"B48","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1038\/nn.3322","article-title":"Experience-dependent modification of a central amygdala fear circuit.","volume":"16","author":"Li","year":"2013","journal-title":"Nat. Neurosci"},{"key":"B49","doi-asserted-by":"publisher","first-page":"4345","DOI":"10.1523\/JNEUROSCI.0061-11.2011","article-title":"Pten knockdown in vivo increases excitatory drive onto dentate granule cells.","volume":"31","author":"Luikart","year":"2011","journal-title":"J. Neurosci"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15585\/mmwr.ss7202a1","article-title":"Prevalence and characteristics of autism spectrum disorder among children aged 8 years - autism and developmental disabilities monitoring network, 11 Sites, United States, 2020.","volume":"72","author":"Maenner","year":"2023","journal-title":"MMWR Surveill. Summ"},{"key":"B51","doi-asserted-by":"publisher","first-page":"eaaw5202","DOI":"10.1126\/science.aaw5202","article-title":"Cortical layer-specific critical dynamics triggering perception.","volume":"365","author":"Marshel","year":"2019","journal-title":"Science"},{"key":"B52","doi-asserted-by":"publisher","first-page":"eabq1637","DOI":"10.1126\/sciadv.abq1637","article-title":"Disynaptic specificity of serial information flow for conditioned fear.","volume":"9","author":"Massi","year":"2023","journal-title":"Sci. Adv"},{"key":"B53","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1002\/(SICI)1096-8628(19991215)88:6<729::AID-AJMG26<3.0.CO;2-Q","article-title":"Association study of the NF1 gene and autistic disorder.","volume":"88","author":"Mbarek","year":"1999","journal-title":"Am. J. Med. Genet."},{"key":"B54","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1002\/aur.132","article-title":"Confirmation study of PTEN mutations among individuals with autism or developmental delays\/mental retardation and macrocephaly.","volume":"3","author":"McBride","year":"2010","journal-title":"Autism Res"},{"key":"B55","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1001\/archgenpsychiatry.2011.145","article-title":"Increased rate of amygdala growth in children aged 2 to 4 years with autism spectrum disorders: A longitudinal study.","volume":"69","author":"Nordahl","year":"2012","journal-title":"Arch. Gen. Psychiatry"},{"key":"B56","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.brainres.2007.06.074","article-title":"A seizure-prone phenotype is associated with altered free-running rhythm in Pten mutant mice.","volume":"1168","author":"Ogawa","year":"2007","journal-title":"Brain Res"},{"key":"B57","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.jpsychires.2023.11.014","article-title":"Inhibitory dysfunction and social processing difficulties in autism: A comprehensive narrative review.","volume":"169","author":"Parrella","year":"2024","journal-title":"J. Psychiatr. Res"},{"key":"B58","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1038\/nature09965","article-title":"Shank3 mutant mice display autistic-like behaviours and striatal dysfunction.","volume":"472","author":"Pe\u00e7a","year":"2011","journal-title":"Nature"},{"key":"B59","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.cell.2011.08.040","article-title":"Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits.","volume":"147","author":"Pe\u00f1agarikano","year":"2011","journal-title":"Cell"},{"key":"B60","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1016\/j.tins.2023.06.006","article-title":"From aversive associations to defensive programs: Experience-dependent synaptic modifications in the central amygdala.","volume":"46","author":"Penzo","year":"2023","journal-title":"Trends Neurosci"},{"key":"B61","doi-asserted-by":"publisher","first-page":"2432","DOI":"10.1523\/JNEUROSCI.4166-13.2014","article-title":"Fear conditioning potentiates synaptic transmission onto long-range projection neurons in the lateral subdivision of central amygdala.","volume":"34","author":"Penzo","year":"2014","journal-title":"J. Neurosci"},{"key":"B62","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1093\/cercor\/bhz103","article-title":"PTEN activity defines an axis for plasticity at cortico-amygdala synapses and influences social behavior.","volume":"30","author":"S\u00e1nchez-Puelles","year":"2020","journal-title":"Cereb. Cortex"},{"key":"B63","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.nbd.2017.08.014","article-title":"PTEN deletion increases hippocampal granule cell excitability in male and female mice.","volume":"108","author":"Santos","year":"2017","journal-title":"Neurobiol. Dis"},{"key":"B64","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1016\/j.cell.2019.12.036","article-title":"Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism.","volume":"180","author":"Satterstrom","year":"2020","journal-title":"Cell"},{"key":"B65","doi-asserted-by":"publisher","first-page":"7674","DOI":"10.1523\/JNEUROSCI.1285-06.2006","article-title":"Stereological analysis of amygdala neuron number in autism.","volume":"26","author":"Schumann","year":"2006","journal-title":"J. Neurosci"},{"key":"B66","doi-asserted-by":"publisher","first-page":"6392","DOI":"10.1523\/JNEUROSCI.1297-04.2004","article-title":"The amygdala is enlarged in children but not adolescents with autism; the hippocampus is enlarged at all ages.","volume":"24","author":"Schumann","year":"2004","journal-title":"J. Neurosci"},{"key":"B67","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s13041-021-00731-8","article-title":"Conditional Pten knockout in parvalbumin- or somatostatin-positive neurons sufficiently leads to autism-related behavioral phenotypes.","volume":"14","author":"Shin","year":"2021","journal-title":"Mol. Brain"},{"key":"B68","first-page":"387","article-title":"Dendritic organization in the neurons of the visual and motor cortices of the cat.","volume":"87","author":"Sholl","year":"1953","journal-title":"J. Anat."},{"key":"B69","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1159\/000504782","article-title":"The role of PTEN in neurodevelopment.","volume":"5","author":"Skelton","year":"2020","journal-title":"Mol. Neuropsychiatry"},{"key":"B70","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1113\/jphysiol.2011.220236","article-title":"Phosphatase and tensin homologue (PTEN) regulates synaptic plasticity independently of its effect on neuronal morphology and migration.","volume":"590","author":"Sperow","year":"2012","journal-title":"J. Physiol"},{"key":"B71","doi-asserted-by":"publisher","first-page":"4738","DOI":"10.1073\/pnas.1222803110","article-title":"Dysregulation of synaptic plasticity precedes appearance of morphological defects in a Pten conditional knockout mouse model of autism.","volume":"110","author":"Takeuchi","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"B72","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1016\/j.neuron.2011.07.026","article-title":"A resource of Cre driver lines for genetic targeting of GABAergic neurons in cerebral cortex.","volume":"71","author":"Taniguchi","year":"2011","journal-title":"Neuron"},{"key":"B73","doi-asserted-by":"publisher","first-page":"111574","DOI":"10.1016\/j.celrep.2022.111574","article-title":"Disruption of mTORC1 rescues neuronal overgrowth and synapse function dysregulated by Pten loss.","volume":"41","author":"Tariq","year":"2022","journal-title":"Cell Rep"},{"key":"B74","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s13064-018-0105-x","article-title":"Homeostatic plasticity in neural development.","volume":"13","author":"Tien","year":"2018","journal-title":"Neural Dev"},{"key":"B75","doi-asserted-by":"publisher","first-page":"3212","DOI":"10.1093\/hmg\/ddu031","article-title":"Germline disruption of Pten localization causes enhanced sex-dependent social motivation and increased glial production.","volume":"23","author":"Tilot","year":"2014","journal-title":"Hum. Mol. Genet"},{"key":"B76","doi-asserted-by":"publisher","first-page":"1996","DOI":"10.1016\/j.cellsig.2007.05.004","article-title":"Dominant role of GABAB2 and Gbetagamma for GABAB receptor-mediated-ERK1\/2\/CREB pathway in cerebellar neurons.","volume":"19","author":"Tu","year":"2007","journal-title":"Cell Signal"},{"key":"B77","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1097\/GIM.0b013e31818fd762","article-title":"The prevalence of PTEN mutations in a clinical pediatric cohort with autism spectrum disorders, developmental delay, and macrocephaly.","volume":"11","author":"Varga","year":"2009","journal-title":"Genet. Med"},{"key":"B78","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1016\/j.celrep.2015.04.019","article-title":"The parvalbumin\/somatostatin ratio is increased in Pten mutant mice and by human PTEN ASD alleles.","volume":"11","author":"Vogt","year":"2015","journal-title":"Cell Rep"},{"key":"B79","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1523\/JNEUROSCI.3144-14.2015","article-title":"Hyperactivity of newborn Pten knock-out neurons results from increased excitatory synaptic drive.","volume":"35","author":"Williams","year":"2015","journal-title":"J. Neurosci"},{"key":"B80","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1038\/nature10360","article-title":"Neocortical excitation\/inhibition balance in information processing and social dysfunction.","volume":"477","author":"Yizhar","year":"2011","journal-title":"Nature"},{"key":"B81","doi-asserted-by":"publisher","first-page":"10468","DOI":"10.1038\/srep10468","article-title":"GABAB receptor upregulates fragile X mental retardation protein expression in neurons.","volume":"5","author":"Zhang","year":"2015","journal-title":"Sci. Rep"},{"key":"B82","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1523\/JNEUROSCI.5685-08.2009","article-title":"Pharmacological inhibition of mTORC1 suppresses anatomical, cellular, and behavioral abnormalities in neural-specific Pten knock-out mice.","volume":"29","author":"Zhou","year":"2009","journal-title":"J. Neurosci"}],"container-title":["Frontiers in Cellular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2025.1597131\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T05:29:53Z","timestamp":1750915793000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2025.1597131\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,26]]},"references-count":82,"alternative-id":["10.3389\/fncel.2025.1597131"],"URL":"https:\/\/doi.org\/10.3389\/fncel.2025.1597131","relation":{},"ISSN":["1662-5102"],"issn-type":[{"value":"1662-5102","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,26]]},"article-number":"1597131"}}