{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:09:45Z","timestamp":1772168985893,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/f1000research.20604.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000}},{"DOI":"10.12688\/f1000research.20604.2","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000}},{"DOI":"10.12688\/f1000research.20604.3","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000}}],"reference-count":17,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R15S088776"],"award-info":[{"award-number":["R15S088776"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007492","name":"Baylor University","doi-asserted-by":"crossref","award":["URSA"],"award-info":[{"award-number":["URSA"]}],"id":[{"id":"10.13039\/100007492","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"\n Background Deficits in sensorimotor gating have been reported in individuals with autism spectrum disorder (ASD), as well as in ASD murine models. However, this behavior has not been examined in the neuronal subset-specific (NS)-\n Pten<\/ns4:italic>\n knockout (KO) model of ASD.\n NS-Pten<\/ns4:italic>\n KO mice exhibit hyperactivity of the PI3K\/AKT\/mTOR signaling pathway which is implicated in the onset of autistic deficits. This study investigates the potential relationship between PI3K\/AKT\/mTOR signaling and deficits in sensorimotor gating. Methods To assess sensorimotor gating in NS-\n Pten<\/ns4:italic>\n KO mice we utilized a three-day paradigm. On day 1 (habituation) the mice were administered 80 repetitions of a 120-dB startle stimulus. On day 2, prepulse inhibition was measured with 90 trials of the startle stimulus that was paired with a smaller (2, 7, or 12 dB) prepulse stimulus. Day 3 was assessed one week later, consisting of randomized startle trials and trials with no stimulus and was used to determine the startle response. Results No significant difference between NS-\n Pten<\/ns4:italic>\n KO or wildtype (WT) mice was found for habituation (\n p<\/ns4:italic>\n > 0.05). No significant differences were found between groups when assessing the percentage of prepulse inhibition at 2, 7, and 12 dB (\n p<\/ns4:italic>\n > 0.05). There was also no difference in startle response between groups (\n p<\/ns4:italic>\n > 0.05). Conclusion Our study found that the NS-\n Pten<\/ns4:italic>\n KO model does not display significant deficits in sensorimotor gating processes. The present findings help to elucidate the relationship between PI3K\/AKT\/mTOR hyperactivation and sensory reactivity.\n <\/ns4:p>","DOI":"10.12688\/f1000research.20604.4","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T05:55:07Z","timestamp":1736834107000},"page":"1727","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuronal subset-specific Pten-deficient mice do not exhibit deficits in sensorimotor gating processes"],"prefix":"10.12688","volume":"8","author":[{"given":"Matthew S.","family":"Binder","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne O.","family":"Nolan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6874-8718","authenticated-orcid":false,"given":"Joaquin N.","family":"Lugo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2025,1,14]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"251-318","DOI":"10.1007\/7854_2011_195","article-title":"Genetic models of sensorimotor gating: relevance to neuropsychiatric disorders.","volume":"12","author":"S Powell","year":"2012","journal-title":"Curr Top Behav Neurosci."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"285-302","DOI":"10.1016\/B978-0-12-800981-9.00017-1","article-title":"Chapter 17 - Dimensional deconstruction and reconstruction of CNV-associated neuropsychiatric disorders.","volume":"23","author":"N Hiroi","year":"2016"},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"94-103","DOI":"10.1002\/aur.1337","article-title":"Increased prepulse inhibition and sensitization of the startle reflex in autistic children.","volume":"7","author":"G Madsen","year":"2014","journal-title":"Autism Res."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"202","DOI":"10.3389\/fnbeh.2016.00202","article-title":"Reduced prepulse inhibition as a biomarker of schizophrenia.","volume":"10","author":"A Mena","year":"2016","journal-title":"Front Behav Neurosci."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"102-110","DOI":"10.9758\/cpn.2011.9.3.102","article-title":"Prepulse inhibition of startle response: recent advances in human studies of psychiatric disease.","volume":"9","author":"H Takahashi","year":"2011","journal-title":"Clin Psychopharmacol Neurosci."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"417-25","DOI":"10.1038\/sj.mp.4001432","article-title":"Sensorimotor gating abnormalities in young males with fragile X syndrome and Fmr1-knockout mice.","volume":"9","author":"P Frankland","year":"2004","journal-title":"Mol Psychiatry."},{"key":"ref-7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0134572","article-title":"Comprehensive analysis of the 16p11.2 deletion and null Cntnap2 mouse models of Autism Spectrum Disorder.","volume":"10","author":"D Brunner","year":"2015","journal-title":"PLoS One."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"283-96","DOI":"10.1038\/nrm3330","article-title":"The functions and regulation of the PTEN tumour suppressor.","volume":"13","author":"M Song","year":"2012","journal-title":"Nat Rev Mol Cell Biol."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"27","DOI":"10.3389\/fnmol.2014.00027","article-title":"Deletion of PTEN produces autism-like behavioral deficits and alterations in synaptic proteins.","volume":"7","author":"J Lugo","year":"2014","journal-title":"Front Mol Neurosci."},{"key":"ref-10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2019.112189","article-title":"NS-Pten adult knockout mice display both quantitative and qualitative changes in urine-induced ultrasonic vocalizations.","volume":"378","author":"M Binder","year":"2020","journal-title":"Behav Brain Res."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"377-388","DOI":"10.1016\/j.neuron.2006.03.023","article-title":"Pten regulates neuronal arborization and social interaction in mice.","volume":"50","author":"C Kwon","year":"2006","journal-title":"Neuron."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"24-29","DOI":"10.1016\/j.brainres.2019.05.029","article-title":"Genetic reduction of MMP-9 in the Fmr1 KO mouse partially rescues prepulse inhibition of acoustic startle response.","volume":"1719","author":"J Kokash","year":"2019","journal-title":"Brain Res."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"35-41","DOI":"10.1038\/sj.mp.4001404","article-title":"Assessment of a prepulse inhibition deficit in a mutant mouse lacking mGlu5 receptors.","volume":"9","author":"S Brody","year":"2004","journal-title":"Mol Psychiatry."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"12923-8","DOI":"10.1073\/pnas.2132711100","article-title":"mTor is required for hypertrophy of Pten-deficient neuronal soma in vivo.","volume":"100","author":"C Kwon","year":"2003","journal-title":"Proc Natl Acad Sci U S A."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"130-135","DOI":"10.1002\/gene.20197","article-title":"Neuron-specific enolase-cre mouse line with cre activity in specific neuronal populations.","volume":"44","author":"C Kwon","year":"2006","journal-title":"Genesis."},{"key":"ref-16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0262916","article-title":"Dietary rescue of adult behavioral deficits in the Fmr1 knockout mouse.","volume":"17","author":"S Nolan","year":"2022","journal-title":"PLoS One."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"156-164","DOI":"10.1016\/j.nbd.2011.07.018","article-title":"Impaired social interactions and motor learning skills in tuberous sclerosis complex model mice expressing a dominant\/negative form of tuberin.","volume":"45","author":"I Ch\u00e9vere-Torres","year":"2012","journal-title":"Neurobiol Dis."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/8-1727\/v4\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/8-1727\/v4\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/8-1727\/v4\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T05:55:10Z","timestamp":1736834110000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/8-1727\/v4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,14]]},"references-count":17,"URL":"https:\/\/doi.org\/10.12688\/f1000research.20604.4","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/f1000research.20604.3","asserted-by":"subject"},{"id-type":"doi","id":"10.12688\/f1000research.20604.2","asserted-by":"subject"},{"id-type":"doi","id":"10.12688\/f1000research.20604.1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.176932.r359040","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.176932.r359041","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,14]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/8-1727\/v4#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.25489.r62086, Benjamin K. Yee, Department of Rehabilitation Sciences, Hong Kong Polytechnic University, Hong Kong, 14 Apr 2020, version 3, indexed","URL":"https:\/\/f1000research.com\/articles\/8-1727\/v3#referee-response-62086","order":0,"name":"referee-response-62086","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.22655.r54867, Maarten van den Buuse, School of Psychology and Public Health, La Trobe University, Melbourne, Vic, 08 Nov 2019, version 1, 1 approved with reservations, 1 not approved","URL":"https:\/\/f1000research.com\/articles\/8-1727\/v1#referee-response-54867","order":1,"name":"referee-response-54867","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"Joaquin Lugo<\/b>; \nPosted: 04 Feb 2020<\/i>; Reviewer 2. The original comments are first followed by a bullet point with our response.Abstract, background:"has been rarely examined\u201d - does this mean it has been examined once before? What was the result? Thank you for your comment. The sentence has been modified to clarify that no other study has assessed prepulse inhibition in neuronal subset specific KO mice.  Introduction: It would be helpful if the neuronal subset-specific Pten KO mouse was described in more detail. What do we know about behavioural changes in this mouse model. Importantly, were there deficits in social behaviour? If this has not been published yet, it would be good to add some of those additional behavioural tests here. Per your insight, a sentence has been added into the introduction that details the established behavioral phenotype of NS-\nPten<\/i> KO mice, clarifying that this model presents with deficits in repetitive behavior, sociability, and communication.   Methods, subjects: Why were only males included in the study? Previous studies investigating the adult phenotype in the NS-\nPten<\/i> model only assessed males (see citations 9 and 10 in the document). Moreover, a similar study that assessed PPI using the Nse-\nPten<\/i> mouse also only investigated males (citation 11). In order to best align our study with other pertinent studies, and to provide similar points of comparison, we also only assessed male mice, acting in accordance with the literature.   Methods, sensorimotor gating:As far as I know, the SR-LAB system has only one speaker and there is no \u201chigh-frequency\u201d speaker (what is that anyway) to produce the stimuli. It has been clarified in the methods that 1 speaker was used to generate the white noise and startle stimuli.                Methods, sensorimotor gating:It would be more clear if the prepulses were described as level over background, i.e. PP2, PP7 and PP12.  Thank you for your suggestion, the methods have been changed to discuss the prepulses used as being relative to the background noise.   Methods, sensorimotor gating:What was the interval between the onset of the prepulse and the onset of the startle pulse (SOA)? What was the interval between various trials in the PPI protocol (ITI)? Is it, like the figure legend suggests, always 15 seconds? This would be unusual because the ITI is variable in most of the PPI literature. The methods section has been modified to state that the SOA was 100 ms and to clarify that the ITI in the PPI procedure was an average of 15 seconds with individual trials ranging from 7-23 seconds.    Results:Details of the statistical analysis are missing. In the Statistical Analysis section in the Methods, or in the Results section, it has to be explained what the between-group and within-group factors are and main effects and importantly interactions between those factors have to be detailed. For example, for PPI, was there a prepulse intensity x genotype interaction? Per your insight, the statistical analysis section now clarifies what the between subjects and within subjects\u2019 factors are for each test day. Additionally, the results section has been amended to make it clearer that there were no main effects or interactions present for any test day.  Discussion:Again, it would be more clear if the prepulses were described as level over background, i.e. PP2, PP7 and PP12. This would allow better comparison with previous studies.  The discussion section now refers to the prepulses in terms of their increase over the background level (ppi 2,7, and 12 dB) in order to make clearer comparisons to other studies.   Figure 1:Along the horizontal axis do not use labels at an angle.  The labels on the x axis for all figures are now horizontal.  Figure 1, legend:A lot of technical detail here should be included in the Methods section, not in a figure legend. There is also no need to constantly repeat rise-fall times. This can be mentioned once in the Methods as a feature of all stimuli. The detail concerning each testing day has been moved to the methods section. Also, the rise fall times are now only mentioned once.","URL":"https:\/\/f1000research.com\/articles\/8-1727\/v4#referee-comment-5196","order":2,"name":"referee-comment-5196","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.25489.r343972, George Leondaritis, Charalampos Brakatselos, Department of Pharmacology, Faculty of Medicine, and Institute of Biosciences, University Research Center of Ioannina (URCI), University of Ioannina, Ioannina, 02 Jan 2025, version 3, indexed","URL":"https:\/\/f1000research.com\/articles\/8-1727\/v3#referee-response-343972","order":3,"name":"referee-response-343972","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"Joaquin Lugo<\/b>; \nPosted: 10 Jan 2025<\/i>; Response1: Thank you for your comments. We have added a paragraph to the conclusion that discusses specific limitations of our study.   We have also clarified that white noise bursts were used in the methods section of the paper Response2: You raise excellent points. We have significantly expanded the discussion section to more precisely detail differences between our model and the comparison studies. We have also clarified that the level of mTOR activation is similar across the models. Lastly, we have discussed the seizure phenotype in both models in more depth and acknowledged that seizures may have had a possible effect on sensorimotor gating behavior.","URL":"https:\/\/f1000research.com\/articles\/8-1727\/v4#referee-comment-13115","order":4,"name":"referee-comment-13115","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by the National Institutes of Health grant R15S088776 and by Baylor University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":5,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}