{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T22:40:36Z","timestamp":1781131236404,"version":"3.54.1"},"reference-count":77,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":17,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100007797","name":"University of Helsinki","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007797","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Molecular Autism"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>MECP2<\/jats:italic>\n                      gene is located on the X chromosome and encodes a methyl-CpG-binding protein 2 involved in transcriptional regulation. Loss-of-function mutations in the\n                      <jats:italic>MECP2<\/jats:italic>\n                      gene lead to Rett syndrome, a severe neurodevelopmental disorder. The clinical picture of Rett syndrome includes, among other symptoms, social deficits, learning impairment, and heightened anxiety. The amygdala is a brain region responsible for emotional learning and is involved in the regulation of social behaviour as well as fear and anxiety. Parvalbumin interneurons tightly control the excitability, oscillation and synchronisation of the amygdala network, which are relevant to its functions. Here, we investigated the effects of\n                      <jats:italic>Mecp2<\/jats:italic>\n                      gene ablation in parvalbumin interneurons on the microcircuit and functional connectivity of the mouse amygdala.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male mice with conditional knockout of the\n                      <jats:italic>Mecp2<\/jats:italic>\n                      gene in parvalbumin interneurons were used as a genetic mouse model. Littermates with an intact gene were used as controls. Ex vivo brain slice electrophysiology, combined with pharmacology and optogenetics, was utilised to characterise microcircuits within the lateral amygdala. In vivo functional ultrasound imaging was used to visualise the connectivity within the amygdala\u2013ventral hippocampus\u2013prefrontal cortex network triad.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Loss of\n                      <jats:italic>Mecp2<\/jats:italic>\n                      in parvalbumin interneurons significantly attenuated GABAergic synaptic input to principal neurons in the lateral amygdala. The deficit in inhibition was accompanied by higher excitability of local principal neurons in adult animals. A deficient in vivo functional connectivity of the amygdala with the ventral hippocampus and prefrontal cortex was observed in conditional knockouts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Limitations<\/jats:title>\n                    <jats:p>\n                      This study used only male mice.\n                      <jats:italic>Mecp2<\/jats:italic>\n                      knockout males exhibit shorter latency to symptom onset and lower phenotypic variability, making them suitable for mechanistic studies. Since previous studies in the field used males, we aimed to advance the existing body of research using the same approach. Finally, the link between the effects observed and possible behavioural alterations needs further investigation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our study characterised the consequences of\n                      <jats:italic>Mecp2<\/jats:italic>\n                      loss in parvalbumin interneurons on amygdala microcircuit function and connectivity within the prefrontal cortex\u2012amygdala\u2012hippocampus triad. It also provided evidence that supports and complements previous findings on the role of interneurons in the functional deficits observed in\n                      <jats:italic>Mecp2<\/jats:italic>\n                      knockout animal models.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13229-025-00699-5","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T16:28:28Z","timestamp":1767630508000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Loss of the Mecp2 gene in parvalbumin interneurons leads to an inhibitory deficit in the amygdala and affects its functional connectivity"],"prefix":"10.1186","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5970-7666","authenticated-orcid":false,"given":"Maj","family":"Liiwand","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2432-0837","authenticated-orcid":false,"given":"Joni","family":"Haikonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7916-693X","authenticated-orcid":false,"given":"Bojana","family":"Kokinovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4061-4563","authenticated-orcid":false,"given":"Svetlana M.","family":"Molchanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9332-3340","authenticated-orcid":false,"given":"Teemu","family":"Aitta-aho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5895-1357","authenticated-orcid":false,"given":"Sari E.","family":"Lauri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8201-817X","authenticated-orcid":false,"given":"Maria","family":"Ryazantseva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"issue":"1","key":"699_CR1","doi-asserted-by":"crossref","first-page":"S147","DOI":"10.1016\/S0387-7604(01)00376-X","volume":"23 Suppl","author":"V den Veyver Ib","year":"2001","unstructured":"den Veyver Ib V, Zoghbi HY. Mutations in the gene encoding methyl-CpG-binding protein 2 cause Rett syndrome. Brain Dev. 2001;23 Suppl(1):S147\u2013151.","journal-title":"Brain Dev"},{"key":"699_CR2","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1126\/science.1153252","volume":"320","author":"M Chahrour","year":"2008","unstructured":"Chahrour M, Jung SY, Shaw C, Zhou X, Wong STC, Qin J, et al. MeCP2, a key contributor to neurological disease, activates and represses transcription. Science. 2008;320:1224\u201329.","journal-title":"Science"},{"key":"699_CR3","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s13229-017-0157-5","volume":"8","author":"Z Wen","year":"2017","unstructured":"Wen Z, Cheng T-L, Li G, Sun S-B, Yu S-Y, Zhang Y, et al. Identification of autism-related Mecp2 mutations by whole-exome sequencing and functional validation. Mol Autism. 2017;8:43.","journal-title":"Mol Autism"},{"key":"699_CR4","doi-asserted-by":"crossref","first-page":"2813","DOI":"10.2147\/NDT.S371483","volume":"18","author":"BE Collins","year":"2022","unstructured":"Collins BE, Neul JL. Rett syndrome and Mecp2 duplication syndrome: disorders of Mecp2 dosage. Neuropsychiatr Dis Treat. 2022;18:2813\u201335.","journal-title":"Neuropsychiatr Dis Treat"},{"key":"699_CR5","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/nature09582","volume":"468","author":"H-T Chao","year":"2010","unstructured":"Chao H-T, Chen H, Samaco RC, Xue M, Chahrour M, Yoo J, et al. Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes. Nature. 2010;468:263\u201369.","journal-title":"Nature"},{"key":"699_CR6","doi-asserted-by":"crossref","first-page":"e14198","DOI":"10.7554\/eLife.14198","volume":"5","author":"K Ure","year":"2016","unstructured":"Ure K, Lu H, Wang W, Ito-Ishida A, Wu Z, He L-J, et al. Restoration of Mecp2 expression in GABAergic neurons is sufficient to rescue multiple disease features in a mouse model of Rett syndrome. Elife. 2016;5:e14198.","journal-title":"Elife"},{"key":"699_CR7","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.neuron.2015.10.029","volume":"88","author":"A Ito-Ishida","year":"2015","unstructured":"Ito-Ishida A, Ure K, Chen H, Swann JW, Zoghbi HY. Loss of Mecp2 in parvalbumin-and somatostatin-expressing neurons in mice leads to Distinct Rett syndrome-like phenotypes. Neuron. 2015;88:651\u201358.","journal-title":"Neuron"},{"key":"699_CR8","doi-asserted-by":"crossref","first-page":"6745","DOI":"10.1523\/JNEUROSCI.0838-23.2023","volume":"43","author":"DD Rupert","year":"2023","unstructured":"Rupert DD, Pagliaro AH, Choe J, Shea SD. Selective deletion of Methyl CpG binding protein 2 from parvalbumin interneurons in the auditory cortex delays the onset of maternal Retrieval in mice. J Neurosci Soc Neurosci. 2023;43:6745\u201359.","journal-title":"J Neurosci Soc Neurosci"},{"key":"699_CR9","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/s41386-020-0778-9","volume":"46","author":"JB Ruden","year":"2021","unstructured":"Ruden JB, Dugan LL, Konradi C. Parvalbumin interneuron vulnerability and brain disorders. Neuropsychopharmacology. Nature Publishing Group. 2021;46:279.","journal-title":"Neuropsychopharmacology. Nature Publishing Group"},{"key":"699_CR10","doi-asserted-by":"publisher","first-page":"e525","DOI":"10.1038\/tp.2015.19","volume":"5","author":"M W\u00f6hr","year":"2015","unstructured":"W\u00f6hr M, Orduz D, Gregory P, Moreno H, Khan U, V\u00f6rckel KJ, et al. Lack of parvalbumin in mice leads to behavioral deficits relevant to all human autism core symptoms and related neural morphofunctional abnormalities. Transl Psychiatry. Nature Publishing Group. 2015;5:e525\u2013525. https:\/\/doi.org\/10.1038\/tp.2015.19.","journal-title":"Transl Psychiatry. Nature Publishing Group"},{"key":"699_CR11","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13041-016-0192-8","volume":"9","author":"F Filice","year":"2016","unstructured":"Filice F, V\u00f6rckel KJ, Sungur A\u00d6, W\u00f6hr M, Schwaller B. Reduction in parvalbumin expression not loss of the parvalbumin-expressing GABA interneuron subpopulation in genetic parvalbumin and shank mouse models of autism. Mol Brain. 2016;9:10.","journal-title":"Mol Brain"},{"key":"699_CR12","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1038\/s41593-024-01676-6","volume":"27","author":"M Abatis","year":"2024","unstructured":"Abatis M, Perin R, Niu R, van den Burg E, Hegoburu C, Kim R, et al. Fear learning induces synaptic potentiation between engram neurons in the rat lateral amygdala. Nat Neurosci. Nature Publishing Group. 2024;27:1309\u201317.","journal-title":"Nat Neurosci. Nature Publishing Group"},{"key":"699_CR13","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.neuron.2016.06.032","volume":"91","author":"EK Lucas","year":"2016","unstructured":"Lucas EK, Jegarl AM, Morishita H, Clem RL. Multimodal and site-specific plasticity of amygdala parvalbumin interneurons after fear learning. Neuron. 2016;91:629\u201343.","journal-title":"Neuron"},{"key":"699_CR14","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nature13258","volume":"509","author":"SBE Wolff","year":"2014","unstructured":"Wolff SBE, Gr\u00fcndemann J, Tovote P, Krabbe S, Jacobson GA, M\u00fcller C, et al. Amygdala interneuron subtypes control fear learning through disinhibition. Nature. 2014;509:453\u201358.","journal-title":"Nature"},{"key":"699_CR15","doi-asserted-by":"crossref","first-page":"9223","DOI":"10.1523\/JNEUROSCI.2461-20.2021","volume":"41","author":"J-Y Yau","year":"2021","unstructured":"Yau J-Y, Chaichim C, Power JM, McNally GP. The roles of basolateral amygdala parvalbumin neurons in fear learning. J Neurosci. 2021;41:9223\u201334.","journal-title":"J Neurosci"},{"key":"699_CR16","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1016\/j.neuron.2012.12.004","volume":"76","author":"S Durand","year":"2012","unstructured":"Durand S, Patrizi A, Quast KB, Hachigian L, Pavlyuk R, Saxena A, et al. NMDA receptor regulation prevents regression of visual cortical function in the absence of Mecp2. Neuron. 2012;76:1078\u201390.","journal-title":"Neuron"},{"key":"699_CR17","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.neuron.2016.07.018","volume":"91","author":"H Lu","year":"2016","unstructured":"Lu H, Ash RT, He L, Kee SE, Wang W, Yu D, et al. Loss and gain of Mecp2 cause similar hippocampal circuit dysfunction that is rescued by deep brain stimulation in a Rett syndrome mouse model. Neuron. 2016;91:739\u201347.","journal-title":"Neuron"},{"key":"699_CR18","doi-asserted-by":"crossref","first-page":"5036","DOI":"10.1038\/ncomms6036","volume":"5","author":"L He","year":"2014","unstructured":"He L, Liu N, Cheng T, Chen X, Li Y, Shu Y, et al. Conditional deletion of Mecp2 in parvalbumin-expressing GABAergic cells results in the absence of critical period plasticity. Nat Commun. Nature Publishing Group. 2014;5:5036.","journal-title":"Nat Commun. Nature Publishing Group"},{"key":"699_CR19","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1038\/85899","volume":"27","author":"J Guy","year":"2001","unstructured":"Guy J, Hendrich B, Holmes M, Martin JE, Bird A. A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat Genet. 2001;27:322\u201326.","journal-title":"Nat Genet"},{"key":"699_CR20","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","volume":"9","author":"J Schindelin","year":"2012","unstructured":"Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. Nature Publishing Group. 2012;9:676\u201382.","journal-title":"Nat Methods. Nature Publishing Group"},{"key":"699_CR21","doi-asserted-by":"crossref","first-page":"e52798","DOI":"10.7554\/eLife.52798","volume":"9","author":"M Ryazantseva","year":"2020","unstructured":"Ryazantseva M, Englund J, Shintyapina A, Huupponen J, Shteinikov V, Pitk\u00e4nen A, et al. Kainate receptors regulate development of glutamatergic synaptic circuitry in the rodent amygdala. Elife. 2020;9:e52798.","journal-title":"Elife"},{"key":"699_CR22","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/s41398-021-01654-7","volume":"11","author":"J Englund","year":"2021","unstructured":"Englund J, Haikonen J, Shteinikov V, Amarilla SP, Atanasova T, Shintyapina A, et al. Downregulation of kainate receptors regulating GABAergic transmission in amygdala after early life stress is associated with anxiety-like behavior in rodents. Transl Psychiatry. 2021;11:538.","journal-title":"Transl Psychiatry"},{"key":"699_CR23","doi-asserted-by":"crossref","unstructured":"Ting JT, Lee BR, Chong P, Soler-Llavina G, Cobbs C, Koch C, et al. Preparation of acute brain slices using an optimized N-methyl-D-glucamine protective recovery method. J Vis Exp. 2018;53825.","DOI":"10.3791\/53825-v"},{"key":"699_CR24","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1152\/jn.00500.2019","volume":"123","author":"R Yamamoto","year":"2020","unstructured":"Yamamoto R, Furuyama T, Sugai T, Ono M, Pare D, Kato N. Serotonergic control of GABAergic inhibition in the lateral amygdala. J Neurophysiol. Am Physiol Soc. 2020;123:670\u201381.","journal-title":"J Neurophysiol. Am Physiol Soc"},{"key":"699_CR25","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/s41380-020-01009-6","volume":"26","author":"S-Y Peng","year":"2021","unstructured":"Peng S-Y, Shi Z, Zhou D-S, Wang X-Y, Li X-X, Liu X-L, et al. Reduced motor cortex GABABR function following chronic alcohol exposure. Mol Psychiatry. 2021;26:383\u201395.","journal-title":"Mol Psychiatry"},{"key":"699_CR26","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1152\/jn.00824.2014","volume":"114","author":"PM Klenowski","year":"2015","unstructured":"Klenowski PM, Fogarty MJ, Belmer A, Noakes PG, Bellingham MC, Bartlett SE. Structural and functional characterization of dendritic arbors and GABAergic synaptic inputs on interneurons and principal cells in the rat basolateral amygdala. J Neurophysiol. Am Physiol Soc. 2015;114:942\u201357.","journal-title":"J Neurophysiol. Am Physiol Soc"},{"key":"699_CR27","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/978-1-0716-4019-7_18","volume-title":"New aspects in analyzing the synaptic organization of the brain","author":"Y Shi","year":"2024","unstructured":"Shi Y, Cui M, Blume T, Herms J. Intravital imaging and analysis of the structural plasticity of dendritic spines in multiple brain regions. In: L\u00fcbke J, Rollenhagen A, editors. New aspects in analyzing the synaptic organization of the brain. New York: Springer; 2024. p. 395\u2013430."},{"key":"699_CR28","doi-asserted-by":"crossref","first-page":"2815","DOI":"10.21105\/joss.02815","volume":"5","author":"MS Ben-Shachar","year":"2020","unstructured":"Ben-Shachar MS, L\u00fcdecke D, Makowski D. Effectsize: estimation of effect size indices and standardized parameters. J Open Source Softw. 2020;5:2815.","journal-title":"J Open Source Softw"},{"key":"699_CR29","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.1093\/bioinformatics\/btu393","volume":"30","author":"Z Gu","year":"2014","unstructured":"Gu Z, Gu L, Eils R, Schlesner M, Brors B. Circlize implements and enhances circular visualization in R. Bioinformatics. 2014;30:2811\u201312.","journal-title":"Bioinformatics"},{"key":"699_CR30","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1523\/JNEUROSCI.3686-06.2007","volume":"27","author":"AR Woodruff","year":"2007","unstructured":"Woodruff AR, Sah P. Networks of parvalbumin-positive interneurons in the basolateral amygdala. J Neurosci Soc Neurosci. 2007;27:553\u201363.","journal-title":"J Neurosci Soc Neurosci"},{"key":"699_CR31","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1111\/j.1476-5381.1990.tb14186.x","volume":"101","author":"GR Seabrook","year":"1990","unstructured":"Seabrook GR, Howson W, Lacey MG. Electrophysiological characterization of potent agonists and antagonists at pre- and postsynaptic GABAB receptors on neurones in rat brain slices. Br J Pharmacol. 1990;101:949\u201357.","journal-title":"Br J Pharmacol"},{"issue":"12","key":"699_CR32","doi-asserted-by":"crossref","first-page":"3752","DOI":"10.1038\/s41380-024-02641-2","volume":"29","author":"J Haikonen","year":"2024","unstructured":"Haikonen J, Szrinivasan R, Ojanen S, Rhee JK, Ryazantseva M, Sulku J, et al. GluK1 kainate receptors are necessary for functional maturation of parvalbumin interneurons regulating amygdala circuit function. Mol Psychiatry. 2024;29(12):3752\u201368.","journal-title":"Mol Psychiatry"},{"key":"699_CR33","doi-asserted-by":"crossref","first-page":"4883","DOI":"10.1523\/JNEUROSCI.3325-16.2017","volume":"37","author":"T Miyamae","year":"2017","unstructured":"Miyamae T, Chen K, Lewis DA, Gonzalez-Burgos G. Distinct physiological maturation of parvalbumin-positive neuron subtypes in mouse prefrontal cortex. J Neurosci. 2017;37:4883\u2013902.","journal-title":"J Neurosci"},{"key":"699_CR34","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1242\/dev.034439","volume":"136","author":"A Mukhopadhyay","year":"2009","unstructured":"Mukhopadhyay A, McGuire T, Peng C-Y, Kessler JA. Differential effects of BMP signaling on parvalbumin and somatostatin interneuron differentiation. Development. 2009;136:2633\u201342.","journal-title":"Development"},{"key":"699_CR35","doi-asserted-by":"crossref","first-page":"4819","DOI":"10.1113\/jphysiol.2012.237453","volume":"590","author":"DE Ehrlich","year":"2012","unstructured":"Ehrlich DE, Ryan SJ, Rainnie DG. Postnatal development of electrophysiological properties of principal neurons in the rat basolateral amygdala. J Physiol. 2012;590:4819\u201338.","journal-title":"The J Physiol"},{"key":"699_CR36","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1016\/j.neuron.2022.02.012","volume":"110","author":"AO Nunez-Elizalde","year":"2022","unstructured":"Nunez-Elizalde AO, Krumin M, Reddy CB, Montaldo G, Urban A, Harris KD, et al. Neural correlates of blood flow measured by ultrasound. Neuron. 2022;110:1631\u201340.e4.","journal-title":"Neuron"},{"key":"699_CR37","doi-asserted-by":"crossref","first-page":"5023","DOI":"10.1038\/ncomms6023","volume":"5","author":"B-F Osmanski","year":"2014","unstructured":"Osmanski B-F, Pezet S, Ricobaraza A, Lenkei Z, Tanter M. Functional ultrasound imaging of intrinsic connectivity in the living rat brain with high spatiotemporal resolution. Nat Commun. 2014;5:5023.","journal-title":"Nat Commun"},{"key":"699_CR38","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1016\/j.neuron.2015.08.024","volume":"87","author":"M Bazelot","year":"2015","unstructured":"Bazelot M, Bocchio M, Kasugai Y, Fischer D, Dodson PD, Ferraguti F, et al. Hippocampal theta input to the amygdala shapes feedforward inhibition to gate heterosynaptic plasticity. Neuron. 2015;87:1290\u2013303.","journal-title":"Neuron"},{"key":"699_CR39","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.celrep.2017.12.097","volume":"22","author":"A Beyeler","year":"2018","unstructured":"Beyeler A, Chang C-J, Silvestre M, L\u00e9v\u00eaque C, Namburi P, Wildes CP, et al. Organization of valence-encoding and projection-defined neurons in the basolateral amygdala. Cell Rep. 2018;22:905\u201318.","journal-title":"Cell Rep"},{"key":"699_CR40","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/s41593-018-0073-9","volume":"21","author":"R Marek","year":"2018","unstructured":"Marek R, Jin J, Goode TD, Giustino TF, Wang Q, Acca GM, et al. Hippocampus-driven feed-forward inhibition of the prefrontal cortex mediates relapse of extinguished fear. Nat Neurosci. 2018;21:384\u201392.","journal-title":"Nat Neurosci. Nature Publishing Group"},{"key":"699_CR41","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1113\/jphysiol.2012.248575","volume":"591","author":"R Marek","year":"2013","unstructured":"Marek R, Strobel C, Bredy TW, Sah P. The amygdala and medial prefrontal cortex: partners in the fear circuit. J Physiol. 2013;591:2381.","journal-title":"The J Physiol"},{"key":"699_CR42","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0301-0082(98)00003-3","volume":"55","author":"AJ McDonald","year":"1998","unstructured":"McDonald AJ. Cortical pathways to the mammalian amygdala. Prog Neurobiol. 1998;55:257\u2013332.","journal-title":"Prog Neurobiol"},{"key":"699_CR43","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.1007\/s00429-015-1081-0","volume":"221","author":"CJ Reppucci","year":"2015","unstructured":"Reppucci CJ, Petrovich GD. Organization of connections between the amygdala, medial prefrontal cortex, and lateral hypothalamus: a single and double retrograde tracing study in rats. Brain Struct Funct. 2015;221:2937.","journal-title":"Brain Struct Function"},{"key":"699_CR44","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1016\/j.celrep.2017.10.046","volume":"21","author":"LM McGarry","year":"2017","unstructured":"McGarry LM, Carter AG. Prefrontal cortex drives distinct projection neurons in the basolateral amygdala. Cell Rep. Elsevier. 2017;21:1426\u201333.","journal-title":"Cell Rep. Elsevier"},{"key":"699_CR45","first-page":"e64833","volume":"10","author":"NP Achilly","year":"2021","unstructured":"Achilly NP, He L, Kim OA, Ohmae S, Wojaczynski GJ, Lin T, et al. Deleting Mecp2 from the cerebellum rather than its neuronal subtypes causes a delay in motor learning in mice. eLife. 2021;10:e64833.","journal-title":"elife. elife Sci Publications, Ltd"},{"key":"699_CR46","first-page":"64","volume":"8","author":"C H\u00fcbner","year":"2014","unstructured":"H\u00fcbner C, Bosch D, Gall A, L\u00fcthi A, Ehrlich I. Ex vivo dissection of optogenetically activated mPFC and hippocampal inputs to neurons in the basolateral amygdala: implications for fear and emotional memory. Front Behav Neurosci. 2014;8:64.","journal-title":"Front Behav Neurosci"},{"key":"699_CR47","doi-asserted-by":"crossref","unstructured":"Felix-Ortiz AC, Burgos-Robles A, Bhagat ND, Leppla CA, Tye KM. Bidirectional modulation of anxiety-related and social behaviors by amygdala projections to the medial prefrontal cortex. Neuroscience. 2016;321:197\u2013209.","DOI":"10.1016\/j.neuroscience.2015.07.041"},{"key":"699_CR48","doi-asserted-by":"crossref","unstructured":"Janak PH, Tye KM. From circuits to behaviour in the amygdala. Nature. 2015;517:284\u201392.","DOI":"10.1038\/nature14188"},{"key":"699_CR49","doi-asserted-by":"crossref","unstructured":"Huang L, Chen Y, Jin S, Lin L, Duan S, Si K, et al. Organizational principles of amygdalar input-output neuronal circuits. Mol Psychiatry. 2021;26:7118\u201329.","DOI":"10.1038\/s41380-021-01262-3"},{"key":"699_CR50","doi-asserted-by":"crossref","unstructured":"Gangopadhyay P, Chawla M, Dal Monte O, Chang SWC. Prefrontal\u2013amygdala circuits in social decision-making. Nat Neurosci. 2021;24:5\u201318.","DOI":"10.1038\/s41593-020-00738-9"},{"key":"699_CR51","doi-asserted-by":"crossref","unstructured":"Cruces-Solis H, Babaev O, Ali H, Piletti Chatain C, Mykytiuk V, Balekoglu N, et al. Altered theta and beta oscillatory synchrony in a genetic mouse model of pathological anxiety. FASEB J. 2021;35:e21585.","DOI":"10.1096\/fj.202002028RR"},{"key":"699_CR52","doi-asserted-by":"crossref","first-page":"781928","DOI":"10.3389\/fncir.2021.781928","volume":"15","author":"MJ Nigro","year":"2021","unstructured":"Nigro MJ, Kirikae H, Kjelsberg K, Nair RR, Witter MP. Not all that is gold glitters: PV-IRES-Cre mouse line shows low efficiency of labeling of parvalbumin interneurons in the perirhinal cortex. Front Neural Circuits. 2021;15:781928.","journal-title":"Front Neural Circuits"},{"key":"699_CR53","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1093\/hmg\/ddw038","volume":"25","author":"F Du","year":"2016","unstructured":"Du F, Nguyen MVC, Karten A, Felice CA, Mandel G, Ballas N. Acute and crucial requirement for Mecp2 function upon transition from early to late adult stages of brain maturation. Hum Mol Genet. 2016;25:1690\u2013702.","journal-title":"Hum Mol Genet"},{"key":"699_CR54","doi-asserted-by":"crossref","first-page":"3899","DOI":"10.1038\/s41467-022-31578-9","volume":"13","author":"P Xu","year":"2022","unstructured":"Xu P, Yue Y, Su J, Sun X, Du H, Liu Z, et al. Pattern decorrelation in the mouse medial prefrontal cortex enables social preference and requires MeCP2. Nat Commun. 2022;13:3899.","journal-title":"Nat Commun. Nature Publishing Group"},{"key":"699_CR55","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1093\/cercor\/bhv002","volume":"26","author":"MP Sceniak","year":"2016","unstructured":"Sceniak MP, Lang M, Enomoto AC, James Howell C, Hermes DJ, Katz DM. Mechanisms of functional hypoconnectivity in the medial prefrontal cortex of Mecp2 null mice. Cereb Cortex. 2016;26:1938\u201356.","journal-title":"Cereb Cortex"},{"key":"699_CR56","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1152\/jn.00800.2010","volume":"105","author":"G Calfa","year":"2011","unstructured":"Calfa G, Hablitz JJ, Pozzo-Miller L. Network hyperexcitability in hippocampal slices from Mecp2 mutant mice revealed by voltage-sensitive dye imaging. J Neurophysiol. 2011;105:1768\u201384.","journal-title":"J Neurophysiol"},{"key":"699_CR57","doi-asserted-by":"crossref","first-page":"4218","DOI":"10.1523\/JNEUROSCI.4225-08.2009","volume":"29","author":"M Adachi","year":"2009","unstructured":"Adachi M, Autry AE, Covington HE, Monteggia LM. MeCP2-mediated transcription repression in the basolateral amygdala may underlie heightened anxiety in a mouse model of Rett syndrome. J Neurosci. 2009;29:4218\u201327.","journal-title":"J Neurosci"},{"key":"699_CR58","doi-asserted-by":"crossref","first-page":"e11399","DOI":"10.1371\/journal.pone.0011399","volume":"5","author":"F Gambino","year":"2010","unstructured":"Gambino F, Khelfaoui M, Poulain B, Bienvenu T, Chelly J, Humeau Y. Synaptic maturation at cortical projections to the lateral amygdala in a mouse model of Rett syndrome. PLoS ONE. 2010;5:e11399.","journal-title":"PLoS One"},{"key":"699_CR59","doi-asserted-by":"crossref","unstructured":"Li W, Xu X, Pozzo-Miller L. Excitatory synapses are stronger in the hippocampus of Rett syndrome mice due to altered synaptic trafficking of AMPA-type glutamate receptors. Proc National Acad Sci. 2016;113:E1575\u201384.","DOI":"10.1073\/pnas.1517244113"},{"key":"699_CR60","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.biopsych.2023.04.006","volume":"94","author":"E Marron Fernandez de Velasco","year":"2023","unstructured":"Marron Fernandez de Velasco E, Tipps ME, Haider B, Souders A, Aguado C, Rose TR, et al. Ethanol-induced suppression of G protein-gated inwardly rectifying K\u00b1dependent signaling in the basal amygdala. Biol Psychiatry. 2023;94:863\u201374.","journal-title":"Biol Psychiatry"},{"key":"699_CR61","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.neuron.2014.07.026","volume":"83","author":"JM Stujenske","year":"2014","unstructured":"Stujenske JM, Likhtik E, Topiwala MA, Gordon JA. Fear and safety engage competing patterns of theta-gamma coupling in the basolateral amygdala. Neuron. 2014;83:919\u201333.","journal-title":"Neuron"},{"key":"699_CR62","doi-asserted-by":"crossref","unstructured":"Han H-B, Shin H-S, Jeong Y, Kim J, Choi JH. Dynamic switching of neural oscillations in the prefrontal\u2013amygdala circuit for naturalistic freeze-or-flight. Proc National Acad Sci. 2023;120:e2308762120.","DOI":"10.1073\/pnas.2308762120"},{"key":"699_CR63","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.neuron.2017.03.022","volume":"94","author":"M Bocchio","year":"2017","unstructured":"Bocchio M, Nabavi S, Capogna M. Synaptic plasticity, engrams, and network oscillations in amygdala circuits for storage and retrieval of emotional memories. Neuron. 2017;94:731\u201343.","journal-title":"Neuron"},{"key":"699_CR64","doi-asserted-by":"crossref","unstructured":"Amaya KA, Teboul E, Weiss GL, Antonoudiou P, Maguire JL. Basolateral amygdala parvalbumin interneurons coordinate oscillations to drive reward behaviors. Curr Biol. 2024;34:1561-1568.e4","DOI":"10.1016\/j.cub.2024.02.041"},{"key":"699_CR65","doi-asserted-by":"crossref","unstructured":"Fu X, Teboul E, Weiss GL, Antonoudiou P, Borkar CD, Fadok JP, et al. Gq neuromodulation of BLA parvalbumin interneurons induces burst firing and mediates fear-associated network and behavioral state transition in mice. Nat Commun. 2022;13:1290.","DOI":"10.1038\/s41467-022-28928-y"},{"key":"699_CR66","doi-asserted-by":"crossref","unstructured":"Huang Y-C, Chen H-C, Lin Y-T, et al (2024) Dynamic assemblies of parvalbumin interneurons in brain oscillations. Neuron 112:2600-2613.e5.","DOI":"10.1016\/j.neuron.2024.05.015"},{"key":"699_CR67","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1007\/s12264-022-00963-1","volume":"38","author":"X Li","year":"2022","unstructured":"Li X, Nie Y, Niu Q, Guo X, Qiu Z, Wang S. Abnormal prefrontal neural oscillations are associated with social deficits in Mecp2 duplication syndrome. Neurosci Bull. 2022;38:1598\u2013602.","journal-title":"Neurosci Bull"},{"key":"699_CR68","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.neuron.2016.07.018","volume":"91","author":"H Lu","year":"2016","unstructured":"Lu H, Ash RT, He L, Kee SE, Wang W, Yu D, et al. Loss and gain of Mecp2 lead to similar hippocampal circuit abnormalities that are rescued by deep brain stimulation in a Rett syndrome mouse model. Neuron. 2016;91:739.","journal-title":"Neuron"},{"key":"699_CR69","doi-asserted-by":"crossref","first-page":"e44182","DOI":"10.7554\/eLife.44182","volume":"8","author":"ML Phillips","year":"2019","unstructured":"Phillips ML, Robinson HA, Pozzo-Miller L. Ventral hippocampal projections to the medial prefrontal cortex regulate social memory. Elife. 2019;8:e44182.","journal-title":"Elife"},{"key":"699_CR70","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0306-4522(95)00417-3","volume":"71","author":"AJ Mcdonald","year":"1996","unstructured":"Mcdonald AJ, Mascagni F, Guo L. Projections of the medial and lateral prefrontal cortices to the amygdala: a phaseolus vulgaris leucoagglutinin study in the rat. Neuroscience. 1996;71:55\u201375.","journal-title":"Neuroscience"},{"key":"699_CR71","doi-asserted-by":"crossref","first-page":"17269","DOI":"10.1523\/JNEUROSCI.4095-11.2011","volume":"31","author":"CA Orsini","year":"2011","unstructured":"Orsini CA, Kim JH, Knapska E, Maren S. Hippocampal and prefrontal projections to the basal amygdala mediate contextual regulation of fear after extinction. J Neurosci. 2011;31:17269\u201377.","journal-title":"J Neurosci"},{"key":"699_CR72","doi-asserted-by":"crossref","first-page":"e78428","DOI":"10.7554\/eLife.78428","volume":"11","author":"N Kuga","year":"2022","unstructured":"Kuga N, Abe R, Takano K, Ikegaya Y, Sasaki T. Prefrontal-amygdalar oscillations related to social behavior in mice. eLife. 2022;11:e78428.","journal-title":"eLife"},{"issue":"5","key":"699_CR73","doi-asserted-by":"crossref","first-page":"109747","DOI":"10.1016\/j.isci.2024.109747","volume":"27","author":"ASA Abed","year":"2024","unstructured":"Abed ASA, Allen TV, Ahmed NY, Sellami A, Sontani Y, Rawlinson EC, et al. Parvalbumin interneuron activity in autism underlies susceptibility to PTSD-like memory formation. iScience. 2024;27(5):109747.","journal-title":"iScience"},{"key":"699_CR74","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1038\/s41591-023-02398-1","volume":"29","author":"JL Neul","year":"2023","unstructured":"Neul JL, Percy AK, Benke TA, Berry-Kravis EM, Glaze DG, Marsh ED, et al. Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study. Nat Med. 2023;29:1468\u201375.","journal-title":"Nat Med"},{"key":"699_CR75","doi-asserted-by":"crossref","first-page":"1172805","DOI":"10.3389\/fnins.2023.1172805","volume":"17","author":"M Palmieri","year":"2023","unstructured":"Palmieri M, Pozzer D, Landsberger N. Advanced genetic therapies for the treatment of Rett syndrome: state of the art and future perspectives. Front Neurosci. 2023;17:1172805.","journal-title":"Front Neurosci"},{"key":"699_CR76","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s00335-019-09793-5","volume":"30","author":"N Vashi","year":"2019","unstructured":"Vashi N, Justice MJ. Treating Rett syndrome: from mouse models to human therapies. Mamm Genome. 2019;30:90\u2013110.","journal-title":"Mamm Genome"},{"key":"699_CR77","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1111\/gbb.12070","volume":"12","author":"LR Schaevitz","year":"2013","unstructured":"Schaevitz LR, G\u00f3mez NB, Zhen DP, Berger-Sweeney JE. Mecp2 R168X male and female mutant mice exhibit Rett-like behavioral deficits. Genes Brain Behav. 2013;12:732\u201340.","journal-title":"Genes Brain Behav"}],"container-title":["Molecular Autism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13229-025-00699-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13229-025-00699-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13229-025-00699-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T14:26:19Z","timestamp":1769091979000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13229-025-00699-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,5]]},"references-count":77,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["699"],"URL":"https:\/\/doi.org\/10.1186\/s13229-025-00699-5","relation":{},"ISSN":["2040-2392"],"issn-type":[{"value":"2040-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,5]]},"assertion":[{"value":"10 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal experiments were performed following the University of Helsinki Animal Welfare Guidelines and approved by the National Animal Experiment Board of Finland (license numbers: KEK21-029, ESAVI\/20432\/2022).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"4"}}