1932

Abstract

Recent advances in genomics have revealed a wide spectrum of genetic variants associated with neurodevelopmental disorders at an unprecedented scale. An increasing number of studies have consistently identified mutations—both inherited and de novo—impacting the function of specific brain circuits. This suggests that, during brain development, alterations in distinct neural circuits, cell types, or broad regulatory pathways ultimately shaping synapses might be a dysfunctional process underlying these disorders. Here, we review findings from human studies and animal model research to provide a comprehensive description of synaptic and circuit mechanisms implicated in neurodevelopmental disorders. We discuss how specific synaptic connections might be commonly disrupted in different disorders and the alterations in cognition and behaviors emerging from imbalances in neuronal circuits. Moreover, we review new approaches that have been shown to restore or mitigate dysfunctional processes during specific critical windows of brain development. Considering the heterogeneity of neurodevelopmental disorders, we also highlight the recent progress in developing improved clinical biomarkers and strategies that will help to identify novel therapeutic compounds and opportunities for early intervention.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-genet-072820-023642
2022-11-30
2024-10-12
Loading full text...

Full text loading...

/deliver/fulltext/genet/56/1/annurev-genet-072820-023642.html?itemId=/content/journals/10.1146/annurev-genet-072820-023642&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Achilly NP, Wang W, Zoghbi HY. 2021. Presymptomatic training mitigates functional deficits in a mouse model of Rett syndrome. Nature 592:7855596–600
    [Google Scholar]
  2. 2.
    Allaway KC, Gabitto MI, Wapinski O, Saldi G, Wang C-Y et al. 2021. Genetic and epigenetic coordination of cortical interneuron development. Nature 597:7878693–97
    [Google Scholar]
  3. 3.
    Amaral DG, Schumann CM, Nordahl CW. 2008. Neuroanatomy of autism. Trends Neurosci 31:3137–45
    [Google Scholar]
  4. 4.
    Amegandjin CA, Choudhury M, Jadhav V, Carriço JN, Quintal A et al. 2021. Sensitive period for rescuing parvalbumin interneurons connectivity and social behavior deficits caused by TSC1 loss. Nat. Commun. 12:13653
    [Google Scholar]
  5. 5.
    Amiel J, Rio M, de Pontual L, Redon R, Malan V et al. 2007. Mutations in TCF4, encoding a class I basic helix-loop-helix transcription factor, are responsible for Pitt-Hopkins syndrome, a severe epileptic encephalopathy associated with autonomic dysfunction. Am. J. Hum. Genet. 80:5988–93
    [Google Scholar]
  6. 6.
    Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY 1999. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat. Genet. 23:2185–88
    [Google Scholar]
  7. 7.
    Antoine MW, Langberg T, Schnepel P, Feldman DE. 2019. Increased excitation-inhibition ratio stabilizes synapse and circuit excitability in four autism mouse models. Neuron 101:4648–61.e4
    [Google Scholar]
  8. 8.
    Auerbach BD, Osterweil EK, Bear MF. 2011. Mutations causing syndromic autism define an axis of synaptic pathophysiology. Nature 480:737563–68
    [Google Scholar]
  9. 9.
    Bariselli S, Hörnberg H, Prévost-Solié C, Musardo S, Hatstatt-Burklé L et al. 2018. Role of VTA dopamine neurons and neuroligin 3 in sociability traits related to nonfamiliar conspecific interaction. Nat. Commun. 9:13173
    [Google Scholar]
  10. 10.
    Bariselli S, Tzanoulinou S, Glangetas C, Prévost-Solié C, Pucci L et al. 2016. SHANK3 controls maturation of social reward circuits in the VTA. Nat. Neurosci. 19:7926–34
    [Google Scholar]
  11. 11.
    Barr MS, Farzan F, Tran LC, Chen R, Fitzgerald PB, Daskalakis ZJ. 2010. Evidence for excessive frontal evoked gamma oscillatory activity in schizophrenia during working memory. Schizophr. Res. 121:1–3146–52
    [Google Scholar]
  12. 12.
    Bateup HS, Takasaki KT, Saulnier JL, Denefrio CL, Sabatini BL. 2011. Loss of Tsc1 in vivo impairs hippocampal mGluR-LTD and increases excitatory synaptic function. J. Neurosci. 31:248862–69
    [Google Scholar]
  13. 13.
    Batista-Brito R, Vinck M, Ferguson KA, Chang JT, Laubender D et al. 2017. Developmental dysfunction of VIP interneurons impairs cortical circuits. Neuron 95:4884–95.e9
    [Google Scholar]
  14. 14.
    Baudouin SJ, Gaudias J, Gerharz S, Hatstatt L, Zhou K et al. 2012. Shared synaptic pathophysiology in syndromic and nonsyndromic rodent models of autism. Science 338:6103128–32
    [Google Scholar]
  15. 15.
    Belforte JE, Zsiros V, Sklar ER, Jiang Z, Yu G et al. 2010. Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes. Nat. Neurosci. 13:176–83
    [Google Scholar]
  16. 16.
    Belmonte MK, Yurgelun-Todd DA. 2003. Functional anatomy of impaired selective attention and compensatory processing in autism. Cogn. Brain Res. 17:3651–64
    [Google Scholar]
  17. 17.
    Bernard C, Exposito-Alonso D, Selten M, Sanalidou S, Hanusz-Godoy A et al. 2021. Cortical wiring by synapse-specific control of local protein synthesis. bioRxiv 468364. https://doi.org/10.1101/2021.11.12.468364
    [Crossref]
  18. 18.
    Berryer MH, Chattopadhyaya B, Xing P, Riebe I, Bosoi C et al. 2016. Decrease of SYNGAP1 in GABAergic cells impairs inhibitory synapse connectivity, synaptic inhibition and cognitive function. Nat. Commun. 7:13340
    [Google Scholar]
  19. 19.
    Berry-Kravis EM, Harnett MD, Reines SA, Reese MA, Ethridge LE et al. 2021. Inhibition of phosphodiesterase-4D in adults with fragile X syndrome: a randomized, placebo-controlled, phase 2 clinical trial. Nat. Med. 27:5862–70
    [Google Scholar]
  20. 20.
    Bidinosti M, Botta P, Krüttner S, Proenca CC, Stoehr N et al. 2016. CLK2 inhibition ameliorates autistic features associated with SHANK3 deficiency. Science 351:62781199–1203
    [Google Scholar]
  21. 21.
    Billuart P, Bienvenu T, Ronce N, des Portes V, Vinet MC et al. 1998. Oligophrenin-1 encodes a rhoGAP protein involved in X-linked mental retardation. Nature 392:6679923–26
    [Google Scholar]
  22. 22.
    Birnbaum R, Weinberger DR. 2017. Genetic insights into the neurodevelopmental origins of schizophrenia. Nat. Rev. Neurosci. 18:12727–40
    [Google Scholar]
  23. 23.
    Bourgeois J-P, Goldman-Rakic PS, Rakic P 1994. Synaptogenesis in the prefrontal cortex of rhesus monkeys. Cereb. Cortex 4:178–96
    [Google Scholar]
  24. 24.
    Buxbaum JD, Silverman JM, Smith CJ, Greenberg DA, Kilifarski M et al. 2002. Association between a GABRB3 polymorphism and autism. Mol. Psychiatry 7:3311–16
    [Google Scholar]
  25. 25.
    Cardin JA, Carlén M, Meletis K, Knoblich U, Zhang F et al. 2009. Driving fast-spiking cells induces gamma rhythm and controls sensory responses. Nature 459:7247663–67
    [Google Scholar]
  26. 26.
    Carlén M, Meletis K, Siegle JH, Cardin JA, Futai K et al. 2012. A critical role for NMDA receptors in parvalbumin interneurons for gamma rhythm induction and behavior. Mol. Psychiatry 17:5537–48
    [Google Scholar]
  27. 27.
    Casanova MF, Buxhoeveden DP, Switala AE, Roy E 2002. Minicolumnar pathology in autism. Neurology 58:3428–32
    [Google Scholar]
  28. 28.
    Chao H-T, Zoghbi HY, Rosenmund C. 2007. MeCP2 controls excitatory synaptic strength by regulating glutamatergic synapse number. Neuron 56:158–65
    [Google Scholar]
  29. 29.
    Chaudhry A, Noor A, Degagne B, Baker K, Bok LA et al. 2015. Phenotypic spectrum associated with PTCHD1 deletions and truncating mutations includes intellectual disability and autism spectrum disorder. Clin. Genet. 88:3224–33
    [Google Scholar]
  30. 30.
    Chen Q, Deister CA, Gao X, Guo B, Lynn-Jones T et al. 2020. Dysfunction of cortical GABAergic neurons leads to sensory hyper-reactivity in a Shank3 mouse model of ASD. Nat. Neurosci. 23:4520–32
    [Google Scholar]
  31. 31.
    Chen Y-C, Kuo H-Y, Bornschein U, Takahashi H, Chen S-Y et al. 2016. Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c. Nat. Neurosci. 19:111513–22
    [Google Scholar]
  32. 32.
    Chung DW, Fish KN, Lewis DA. 2016. Pathological basis for deficient excitatory drive to cortical parvalbumin interneurons in schizophrenia. Am. J. Psychiatry 173:111131–39
    [Google Scholar]
  33. 33.
    Clement JP, Aceti M, Creson TK, Ozkan ED, Shi Y et al. 2012. Pathogenic SYNGAP1 mutations impair cognitive development by disrupting maturation of dendritic spine synapses. Cell 151:4709–23
    [Google Scholar]
  34. 34.
    Clemente-Perez A, Makinson SR, Higashikubo B, Brovarney S, Cho FS et al. 2017. Distinct thalamic reticular cell types differentially modulate normal and pathological cortical rhythms. Cell Rep 19:102130–42
    [Google Scholar]
  35. 35.
    Comery TA, Harris JB, Willems PJ, Oostra BA, Irwin SA et al. 1997. Abnormal dendritic spines in fragile X knockout mice: maturation and pruning deficits. PNAS 94:105401–4
    [Google Scholar]
  36. 36.
    Contractor A, Ethell IM, Portera-Cailliau C. 2021. Cortical interneurons in autism. Nat. Neurosci. 24:121648–59
    [Google Scholar]
  37. 37.
    Cotney J, Muhle RA, Sanders SJ, Liu L, Willsey AJ et al. 2015. The autism-associated chromatin modifier CHD8 regulates other autism risk genes during human neurodevelopment. Nat. Commun. 6:6404
    [Google Scholar]
  38. 38.
    Courchesne E, Pierce K. 2005. Why the frontal cortex in autism might be talking only to itself: local over-connectivity but long-distance disconnection. Curr. Opin. Neurobiol. 15:2225–30
    [Google Scholar]
  39. 39.
    Dawes JM, Weir GA, Middleton SJ, Patel R, Chisholm KI et al. 2018. Immune or genetic-mediated disruption of CASPR2 causes pain hypersensitivity due to enhanced primary afferent excitability. Neuron 97:4806–822.e10
    [Google Scholar]
  40. 40.
    De Felipe J, Marco P, Fairén A, Jones EG. 1997. Inhibitory synaptogenesis in mouse somatosensory cortex. Cereb. Cortex 7:7619–34
    [Google Scholar]
  41. 41.
    de la Torre-Ubieta L, Won H, Stein JL, Geschwind DH. 2016. Advancing the understanding of autism disease mechanisms through genetics. Nat. Med. 22:4345–61
    [Google Scholar]
  42. 42.
    De Rubeis S, He X, Goldberg AP, Poultney CS, Samocha K et al. 2014. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature 515:7526209–15
    [Google Scholar]
  43. 43.
    del Pino I, Brotons-Mas JR, Marques-Smith A, Marighetto A, Frick A et al. 2017. Abnormal wiring of CCK+ basket cells disrupts spatial information coding. Nat. Neurosci. 20:784–92
    [Google Scholar]
  44. 44.
    del Pino I, García-Frigola C, Dehorter N, Brotons-Mas JR, Alvarez-Salvado E et al. 2013. Erbb4 deletion from fast-spiking interneurons causes schizophrenia-like phenotypes. Neuron 79:61152–68
    [Google Scholar]
  45. 45.
    D'Gama AM, Walsh CA 2018. Somatic mosaicism and neurodevelopmental disease. Nat. Neurosci. 21:111504–14
    [Google Scholar]
  46. 46.
    Di Martino A, Kelly C, Grzadzinski R, Zuo X-N, Mennes M et al. 2011. Aberrant striatal functional connectivity in children with autism. Biol. Psychiatry 69:9847–56
    [Google Scholar]
  47. 47.
    Dias CM, Walsh CA. 2020. Recent advances in understanding the genetic architecture of autism. Annu. Rev. Genom. Hum. Genet. 21:289–304
    [Google Scholar]
  48. 48.
    Dibbens LM, Feng H-J, Richards MC, Harkin LA, Hodgson BL et al. 2004. GABRD encoding a protein for extra- or peri-synaptic GABAA receptors is a susceptibility locus for generalized epilepsies. Hum. Mol. Genet. 13:131315–19
    [Google Scholar]
  49. 49.
    Dibbens LM, Tarpey PS, Hynes K, Bayly MA, Scheffer IE et al. 2008. X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment. Nat. Genet. 40:6776–81
    [Google Scholar]
  50. 50.
    Doan RN, Bae B-I, Cubelos B, Chang C, Hossain AA et al. 2016. Mutations in human accelerated regions disrupt cognition and social behavior. Cell 167:2341–54.e12
    [Google Scholar]
  51. 51.
    Doan RN, Lim ET, De Rubeis S, Betancur C, Cutler DJ et al. 2019. Recessive gene disruptions in autism spectrum disorder. Nat. Genet. 51:71092–98
    [Google Scholar]
  52. 52.
    Dölen G, Osterweil E, Rao BSS, Smith GB, Auerbach BD et al. 2007. Correction of fragile X syndrome in mice. Neuron 56:6955–62
    [Google Scholar]
  53. 53.
    Durand S, Patrizi A, Quast KB, Hachigian L, Pavlyuk R et al. 2012. NMDA receptor regulation prevents regression of visual cortical function in the absence of Mecp2. Neuron 76:61078–90
    [Google Scholar]
  54. 54.
    Ehninger D, Han S, Shilyansky C, Zhou Y, Li W et al. 2008. Reversal of learning deficits in a Tsc2+/− mouse model of tuberous sclerosis. Nat. Med. 14:8843–48
    [Google Scholar]
  55. 55.
    Ellingford RA, Panasiuk MJ, de Meritens ER, Shaunak R, Naybour L et al. 2021. Cell-type-specific synaptic imbalance and disrupted homeostatic plasticity in cortical circuits of ASD-associated Chd8 haploinsufficient mice. Mol. Psychiatry 26:73614–24
    [Google Scholar]
  56. 56.
    Enard W, Gehre S, Hammerschmidt K, Hölter SM, Blass T et al. 2009. A humanized version of Foxp2 affects cortico-basal ganglia circuits in mice. Cell 137:5961–71
    [Google Scholar]
  57. 57.
    Epi4K Consort., Epilepsy Phenome/Genome Proj 2013. De novo mutations in epileptic encephalopathies. Nature 501:7466217–21
    [Google Scholar]
  58. 58.
    Etherton MR, Blaiss CA, Powell CM, Südhof TC. 2009. Mouse neurexin-1α deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments. PNAS 106:4217998–8003
    [Google Scholar]
  59. 59.
    Exposito-Alonso D, Osório C, Bernard C, Pascual-García S, del Pino I et al. 2020. Subcellular sorting of neuregulins controls the assembly of excitatory-inhibitory cortical circuits. eLife 9:e57000
    [Google Scholar]
  60. 60.
    Favuzzi E, Deogracias R, Marques-Smith A, Maeso P, Jezequel J et al. 2019. Distinct molecular programs regulate synapse specificity in cortical inhibitory circuits. Science 363:6425413–17
    [Google Scholar]
  61. 61.
    Fazzari P, Paternain AV, Valiente M, Pla R, Luján R et al. 2010. Control of cortical GABA circuitry development by Nrg1 and ErbB4 signalling. Nature 464:72931376–80
    [Google Scholar]
  62. 62.
    Flaherty E, Zhu S, Barretto N, Cheng E, Deans PJM et al. 2019. Neuronal impact of patient-specific aberrant NRXN1α splicing. Nat. Genet. 51:121679–90
    [Google Scholar]
  63. 63.
    Földy C, Malenka RC, Südhof TC. 2013. Autism-associated neuroligin-3 mutations commonly disrupt tonic endocannabinoid signaling. Neuron 78:3498–509
    [Google Scholar]
  64. 64.
    Forrest MP, Parnell E, Penzes P 2018. Dendritic structural plasticity and neuropsychiatric disease. Nat. Rev. Neurosci. 19:4215–34
    [Google Scholar]
  65. 65.
    Fu JM, Satterstrom FK, Peng M, Brand H, Collins RL et al. 2021. Rare coding variation illuminates the allelic architecture, risk genes, cellular expression patterns, and phenotypic context of autism. medRxiv 21267194. https://doi.org/10.1101/2021.12.20.21267194
    [Crossref]
  66. 66.
    Gabard-Durnam LJ, Wilkinson C, Kapur K, Tager-Flusberg H, Levin AR, Nelson CA. 2019. Longitudinal EEG power in the first postnatal year differentiates autism outcomes. Nat. Commun. 10:14188
    [Google Scholar]
  67. 67.
    Gabel HW, Kinde B, Stroud H, Gilbert CS, Harmin DA et al. 2015. Disruption of DNA-methylation-dependent long gene repression in Rett syndrome. Nature 522:755489–93
    [Google Scholar]
  68. 68.
    Glantz LA, Lewis DA. 2000. Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch. Gen. Psychiatry 57:165–73
    [Google Scholar]
  69. 69.
    Goel A, Cantu DA, Guilfoyle J, Chaudhari GR, Newadkar A et al. 2018. Impaired perceptual learning in a mouse model of Fragile X syndrome is mediated by parvalbumin neuron dysfunction and is reversible. Nat. Neurosci. 21:101404–11
    [Google Scholar]
  70. 70.
    Goff KM, Goldberg EM. 2019. Vasoactive intestinal peptide-expressing interneurons are impaired in a mouse model of Dravet syndrome. eLife 8:e46846
    [Google Scholar]
  71. 71.
    Gomez AM, Traunmüller L, Scheiffele P. 2021. Neurexins: molecular codes for shaping neuronal synapses. Nat. Rev. Neurosci. 22:3137–51
    [Google Scholar]
  72. 72.
    Gompers AL, Su-Feher L, Ellegood J, Copping NA, Riyadh MA et al. 2017. Germline Chd8 haploinsufficiency alters brain development in mouse. Nat. Neurosci. 20:81062–73
    [Google Scholar]
  73. 73.
    Greenblatt EJ, Spradling AC. 2018. Fragile X mental retardation 1 gene enhances the translation of large autism-related proteins. Science 361:6403709–12
    [Google Scholar]
  74. 74.
    Grove J, Ripke S, Als TD, Mattheisen M, Walters RK et al. 2019. Identification of common genetic risk variants for autism spectrum disorder. Nat. Genet. 51:3431–44
    [Google Scholar]
  75. 75.
    Guy J, Gan J, Selfridge J, Cobb S, Bird A 2007. Reversal of neurological defects in a mouse model of Rett syndrome. Science 315:58151143–47
    [Google Scholar]
  76. 76.
    Haenschel C, Bittner RA, Waltz J, Haertling F, Wibral M et al. 2009. Cortical oscillatory activity is critical for working memory as revealed by deficits in early-onset schizophrenia. J. Neurosci. 29:309481–89
    [Google Scholar]
  77. 77.
    Haldipur P, Millen KJ, Aldinger KA. 2022. Human cerebellar development and transcriptomics: implications for neurodevelopmental disorders. Annu. Rev. Neurosci. 45:515–31
    [Google Scholar]
  78. 78.
    Hamdan FF, Gauthier J, Araki Y, Lin D-T, Yoshizawa Y et al. 2011. Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability. Am. J. Hum. Genet. 88:3306–16
    [Google Scholar]
  79. 79.
    Han K, Holder JL Jr., Schaaf CP, Lu H, Chen H et al. 2013. SHANK3 overexpression causes manic-like behaviour with unique pharmacogenetic properties. Nature 503:747472–77
    [Google Scholar]
  80. 80.
    Harony-Nicolas H, De Rubeis S, Kolevzon A, Buxbaum JD. 2015. Phelan McDermid syndrome: from genetic discoveries to animal models and treatment. J. Child Neurol. 30:141861–70
    [Google Scholar]
  81. 81.
    Hart H, Radua J, Nakao T, Mataix-Cols D, Rubia K 2013. Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects. JAMA Psychiatry 70:2185–98
    [Google Scholar]
  82. 82.
    He CX, Portera-Cailliau C. 2013. The trouble with spines in fragile X syndrome: density, maturity and plasticity. Neuroscience 251:120–28
    [Google Scholar]
  83. 83.
    He JL, Oeltzschner G, Mikkelsen M, Deronda A, Harris AD et al. 2021. Region-specific elevations of glutamate + glutamine correlate with the sensory symptoms of autism spectrum disorders. Transl. Psychiatry 11:1411
    [Google Scholar]
  84. 84.
    Henderson C, Wijetunge L, Kinoshita MN, Shumway M, Hammond RS et al. 2012. Reversal of disease-related pathologies in the fragile X mouse model by selective activation of GABAB receptors with arbaclofen. Sci. Transl. Med. 4:152152ra128
    [Google Scholar]
  85. 85.
    Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG. 2013. Cancer drug resistance: an evolving paradigm. Nat. Rev. Cancer 13:10714–26
    [Google Scholar]
  86. 86.
    Hörnberg H, Pérez-Garci E, Schreiner D, Hatstatt-Burklé L, Magara F et al. 2020. Rescue of oxytocin response and social behaviour in a mouse model of autism. Nature 584:252–56
    [Google Scholar]
  87. 87.
    Hoshina N, Johnson-Venkatesh EM, Hoshina M, Umemori H. 2021. Female-specific synaptic dysfunction and cognitive impairment in a mouse model of PCDH19 disorder. Science 372:6539eaaz3893
    [Google Scholar]
  88. 88.
    Houbaert X, Zhang C-L, Gambino F, Lepleux M, Deshors M et al. 2013. Target-specific vulnerability of excitatory synapses leads to deficits in associative memory in a model of intellectual disorder. J. Neurosci. 33:3413805–19
    [Google Scholar]
  89. 89.
    Howes OD, Murray RM. 2014. Schizophrenia: an integrated sociodevelopmental-cognitive model. Lancet 383:99291677–87
    [Google Scholar]
  90. 90.
    Hu WF, Chahrour MH, Walsh CA. 2014. The diverse genetic landscape of neurodevelopmental disorders. Annu. Rev. Genom. Hum. Genet. 15:195–213
    [Google Scholar]
  91. 91.
    Huang Q, Pereira AC, Velthuis H, Wong NML, Ellis CL et al. 2022. GABAB receptor modulation of visual sensory processing in adults with and without autism spectrum disorder. Sci. Transl. Med. 14:626eabg7859
    [Google Scholar]
  92. 92.
    Hull JV, Dokovna LB, Jacokes ZJ, Torgerson CM, Irimia A, Van Horn JD. 2016. Resting-state functional connectivity in autism spectrum disorders: a review. Front. Psychiatry 7:205
    [Google Scholar]
  93. 93.
    Huttenlocher PR. 1979. Synaptic density in human frontal cortex—developmental changes and effects of aging. Brain Res. 163:2195–205
    [Google Scholar]
  94. 94.
    Ito-Ishida A, Ure K, Chen H, Swann JW, Zoghbi HY. 2015. Loss of MeCP2 in parvalbumin-and somatostatin-expressing neurons in mice leads to distinct Rett syndrome-like phenotypes. Neuron 88:4651–58
    [Google Scholar]
  95. 95.
    Judson MC, Wallace ML, Sidorov MS, Burette AC, Gu B et al. 2016. GABAergic neuron-specific loss of Ube3a causes Angelman syndrome-like EEG abnormalities and enhances seizure susceptibility. Neuron 90:156–69
    [Google Scholar]
  96. 96.
    Jurgensen S, Castillo PE. 2015. Selective dysregulation of hippocampal inhibition in the mouse lacking autism candidate gene CNTNAP2. J. Neurosci. 35:4314681–87
    [Google Scholar]
  97. 97.
    Karayiorgou M, Simon TJ, Gogos JA. 2010. 22q11.2 microdeletions: linking DNA structural variation to brain dysfunction and schizophrenia. Nat. Rev. Neurosci. 11:6402–16
    [Google Scholar]
  98. 98.
    Kasnauskiene J, Ciuladaite Z, Preiksaitiene E, Utkus A, Peciulyte A, Kučinskas V. 2013. A new single gene deletion on 2q34: ERBB4 is associated with intellectual disability. Am. J. Med. Genet. A. 161:61487–90
    [Google Scholar]
  99. 99.
    Katrancha SM, Shaw JE, Zhao AY, Myers SA, Cocco AR et al. 2019. Trio haploinsufficiency causes neurodevelopmental disease-associated deficits. Cell Rep 26:102805–17.e9
    [Google Scholar]
  100. 100.
    Kim H, Ährlund-Richter S, Wang X, Deisseroth K, Carlén M. 2016. Prefrontal parvalbumin neurons in control of attention. Cell 164:1–2208–18
    [Google Scholar]
  101. 101.
    Korotkova T, Fuchs EC, Ponomarenko A, von Engelhardt J, Monyer H. 2010. NMDA receptor ablation on parvalbumin-positive interneurons impairs hippocampal synchrony, spatial representations, and working memory. Neuron 68:3557–69
    [Google Scholar]
  102. 102.
    Kosillo P, Doig NM, Ahmed KM, Agopyan-Miu AHCW, Wong CD et al. 2019. Tsc1-mTORC1 signaling controls striatal dopamine release and cognitive flexibility. Nat. Commun. 10:15426
    [Google Scholar]
  103. 103.
    Kozorovitskiy Y, Saunders A, Johnson CA, Lowell BB, Sabatini BL. 2012. Recurrent network activity drives striatal synaptogenesis. Nature 485:7400646–50
    [Google Scholar]
  104. 104.
    Krigsman A, Walker SJ. 2021. Gastrointestinal disease in children with autism spectrum disorders: etiology or consequence?. World J. Psychiatry 11:9605–18
    [Google Scholar]
  105. 105.
    Krishnan ML, Berry-Kravis E, Capal JK, Carpenter R, Gringras P et al. 2021. Clinical trial strategies for rare neurodevelopmental disorders: challenges and opportunities. Nat. Rev. Drug Discov. 20:9653–54
    [Google Scholar]
  106. 106.
    Krishnan V, Stoppel DC, Nong Y, Johnson MA, Nadler MJS et al. 2017. Autism gene Ube3a and seizures impair sociability by repressing VTA Cbln1. Nature 543:7646507–12
    [Google Scholar]
  107. 107.
    Lai CS, Fisher SE, Hurst JA, Vargha-Khadem F, Monaco AP. 2001. A forkhead-domain gene is mutated in a severe speech and language disorder. Nature 413:6855519–23
    [Google Scholar]
  108. 108.
    Lambe EK, Krimer LS, Goldman-Rakic PS. 2000. Differential postnatal development of catecholamine and serotonin inputs to identified neurons in prefrontal cortex of rhesus monkey. J. Neurosci. 20:238780–87
    [Google Scholar]
  109. 109.
    Le Meur N, Holder-Espinasse M, Jaillard S, Goldenberg A, Joriot S et al. 2010. MEF2C haploinsufficiency caused by either microdeletion of the 5q14.3 region or mutation is responsible for severe mental retardation with stereotypic movements, epilepsy and/or cerebral malformations. J. Med. Genet. 47:122–29
    [Google Scholar]
  110. 110.
    Lewis DA, Cruz D, Eggan S, Erickson S. 2004. Postnatal development of prefrontal inhibitory circuits and the pathophysiology of cognitive dysfunction in schizophrenia. Ann. N. Y. Acad. Sci. 1021:64–76
    [Google Scholar]
  111. 111.
    Lewis DA, Curley AA, Glausier JR, Volk DW. 2012. Cortical parvalbumin interneurons and cognitive dysfunction in schizophrenia. Trends Neurosci 35:157–67
    [Google Scholar]
  112. 112.
    Li J, Pinto-Duarte A, Zander M, Cuoco MS, Lai C-Y et al. 2022. Dnmt3a knockout in excitatory neurons impairs postnatal synapse maturation and increases the repressive histone modification H3K27me3. eLife 11:e66909
    [Google Scholar]
  113. 113.
    Liu S, Zhou L, Yuan H, Vieira M, Sanz-Clemente A et al. 2017. A rare variant identified within the GluN2B C-terminus in a patient with autism affects NMDA receptor surface expression and spine density. J. Neurosci. 37:154093–102
    [Google Scholar]
  114. 114.
    Llamosas N, Michaelson SD, Vaissiere T, Rojas C, Miller CA, Rumbaugh G. 2021. Syngap1 regulates experience-dependent cortical ensemble plasticity by promoting in vivo excitatory synapse strengthening. PNAS 118:34e2100579118
    [Google Scholar]
  115. 115.
    Ma Z-H, Lu B, Li X, Mei T, Guo Y-Q et al. 2022. Atypicalities in the developmental trajectory of cortico-striatal functional connectivity in autism spectrum disorder. Autism 26:5110822
    [Google Scholar]
  116. 116.
    Makinson CD, Tanaka BS, Sorokin JM, Wong JC, Christian CA et al. 2017. Regulation of thalamic and cortical network synchrony by Scn8a. Neuron 93:51165–79.e6
    [Google Scholar]
  117. 117.
    Margolis SS, Salogiannis J, Lipton DM, Mandel-Brehm C, Wills ZP et al. 2010. EphB-mediated degradation of the RhoA GEF Ephexin5 relieves a developmental brake on excitatory synapse formation. Cell 143:3442–55
    [Google Scholar]
  118. 118.
    Marín O. 2012. Interneuron dysfunction in psychiatric disorders. Nat. Rev. Neurosci. 13:2107–20
    [Google Scholar]
  119. 119.
    Marín O. 2016. Developmental timing and critical windows for the treatment of psychiatric disorders. Nat. Med. 22:1229–38
    [Google Scholar]
  120. 120.
    Marques TR, Ashok AH, Angelescu I, Borgan F, Myers J et al. 2021. GABA-A receptor differences in schizophrenia: a positron emission tomography study using [11C]Ro154513. Mol. Psychiatry 26:62616–25
    [Google Scholar]
  121. 121.
    Marro SG, Chanda S, Yang N, Janas JA, Valperga G et al. 2019. Neuroligin-4 regulates excitatory synaptic transmission in human neurons. Neuron 103:P617–26.e6
    [Google Scholar]
  122. 122.
    Maury EA, Sherman MA, Genovese G, Gilgenast TG, Rajarajan P et al. 2022. Schizophrenia-associated somatic copy number variants from 12,834 cases reveal contribution to risk and recurrent, isoform-specific NRXN1 disruptions. medRxiv 21268385. https://doi.org/10.1101/2021.12.24.21268385
    [Crossref]
  123. 123.
    McCutcheon RA, Abi-Dargham A, Howes OD. 2019. Schizophrenia, dopamine and the striatum: from biology to symptoms. Trends Neurosci. 42:3205–20
    [Google Scholar]
  124. 124.
    Mei Y, Monteiro P, Zhou Y, Kim J-A, Gao X et al. 2016. Adult restoration of Shank3 expression rescues selective autistic-like phenotypes. Nature 530:7591481–84
    [Google Scholar]
  125. 125.
    Meisler MH, Hill SF, Yu W 2021. Sodium channelopathies in neurodevelopmental disorders. Nat. Rev. Neurosci. 22:3152–66
    [Google Scholar]
  126. 126.
    Meyer-Lindenberg AS, Olsen RK, Kohn PD, Brown T, Egan MF et al. 2005. Regionally specific disturbance of dorsolateral prefrontal-hippocampal functional connectivity in schizophrenia. Arch. Gen. Psychiatry 62:4379–86
    [Google Scholar]
  127. 127.
    Michaelson SD, Ozkan ED, Aceti M, Maity S, Llamosas N et al. 2018. SYNGAP1 heterozygosity disrupts sensory processing by reducing touch-related activity within somatosensory cortex circuits. Nat. Neurosci. 21:1–13
    [Google Scholar]
  128. 128.
    Millan MJ, Andrieux A, Bartzokis G, Cadenhead K, Dazzan P et al. 2016. Altering the course of schizophrenia: progress and perspectives. Nat. Rev. Drug Discov. 15:485–515
    [Google Scholar]
  129. 129.
    Modinos G, Şimşek F, Azis M, Bossong M, Bonoldi I et al. 2018. Prefrontal GABA levels, hippocampal resting perfusion and the risk of psychosis. Neuropsychopharmacology 43:132652–59
    [Google Scholar]
  130. 130.
    Mohn AR, Gainetdinov RR, Caron MG, Koller BH. 1999. Mice with reduced NMDA receptor expression display behaviors related to schizophrenia. Cell 98:4427–36
    [Google Scholar]
  131. 131.
    Monteiro P, Feng G. 2017. SHANK proteins: roles at the synapse and in autism spectrum disorder. Nat. Rev. Neurosci. 18:3147–57
    [Google Scholar]
  132. 132.
    Mossner JM, Batista-Brito R, Pant R, Cardin JA. 2020. Developmental loss of MeCP2 from VIP interneurons impairs cortical function and behavior. eLife 9:e55639
    [Google Scholar]
  133. 133.
    Mukai J, Cannavò E, Crabtree GW, Sun Z, Diamantopoulou A et al. 2019. Recapitulation and reversal of schizophrenia-related phenotypes in Setd1a-deficient mice. Neuron 104:471–87.e12
    [Google Scholar]
  134. 134.
    Mukherjee A, Carvalho F, Eliez S, Caroni P. 2019. Long-lasting rescue of network and cognitive dysfunction in a genetic schizophrenia model. Cell 178:1387–402.e14
    [Google Scholar]
  135. 135.
    Najmabadi H, Hu H, Garshasbi M, Zemojtel T, Abedini SS et al. 2011. Deep sequencing reveals 50 novel genes for recessive cognitive disorders. Nature 478:736757–63
    [Google Scholar]
  136. 136.
    Nakajima M, Schmitt LI, Feng G, Halassa MM. 2019. Combinatorial targeting of distributed forebrain networks reverses noise hypersensitivity in a model of autism spectrum disorder. Neuron 104:3488–500.e11
    [Google Scholar]
  137. 137.
    Nguyen TA, Wu K, Pandey S, Lehr AW, Li Y et al. 2020. A cluster of autism-associated variants on X-linked NLGN4X functionally resemble NLGN4Y. Neuron 106:5759–68.e7
    [Google Scholar]
  138. 138.
    Orefice LL. 2020. Peripheral somatosensory neuron dysfunction: emerging roles in autism spectrum disorders. Neuroscience 445:120–29
    [Google Scholar]
  139. 139.
    Orefice LL, Mosko JR, Morency DT, Wells MF, Tasnim A et al. 2019. Targeting peripheral somatosensory neurons to improve tactile-related phenotypes in ASD models. Cell 178:4867–86.e24
    [Google Scholar]
  140. 140.
    Orefice LL, Zimmerman AL, Chirila AM, Sleboda SJ, Head JP, Ginty DD. 2016. Peripheral mechanosensory neuron dysfunction underlies tactile and behavioral deficits in mouse models of ASDs. Cell 166:2299–313
    [Google Scholar]
  141. 141.
    Owen MJ, O'Donovan MC. 2017. Schizophrenia and the neurodevelopmental continuum: evidence from genomics. World Psychiatry 16:3227–35
    [Google Scholar]
  142. 142.
    Pak C, Danko T, Mirabella VR, Wang J, Liu Y et al. 2021. Cross-platform validation of neurotransmitter release impairments in schizophrenia patient-derived NRXN1-mutant neurons. PNAS 118:22e2025598118
    [Google Scholar]
  143. 143.
    Paskus JD, Tian C, Fingleton E, Shen C, Chen X et al. 2019. Synaptic Kalirin-7 and Trio interactomes reveal a GEF protein-dependent neuroligin-1 mechanism of action. Cell Rep 29:102944–52.e5
    [Google Scholar]
  144. 144.
    Paulsen B, Velasco S, Kedaigle AJ, Pigoni M, Quadrato G et al. 2022. Autism genes converge on asynchronous development of shared neuron classes. Nature 602:268–73
    [Google Scholar]
  145. 145.
    Peça J, Feliciano C, Ting JT, Wang W, Wells MF et al. 2011. Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature 472:7344437–42
    [Google Scholar]
  146. 146.
    Peixoto RT, Chantranupong L, Hakim R, Levasseur J, Wang W et al. 2019. Abnormal striatal development underlies the early onset of behavioral deficits in Shank3B−/− mice. Cell Rep 29:72016–27.e4
    [Google Scholar]
  147. 147.
    Peixoto RT, Wang W, Croney DM, Kozorovitskiy Y, Sabatini BL. 2016. Early hyperactivity and precocious maturation of corticostriatal circuits in Shank3B−/− mice. Nat. Neurosci. 19:5716–24
    [Google Scholar]
  148. 148.
    Peñagarikano O, Abrahams BS, Herman EI, Winden KD, Gdalyahu A et al. 2011. Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits. Cell 147:1235–46
    [Google Scholar]
  149. 149.
    Petanjek Z, Judaš M, Šimic G, Rasin MR, Uylings HBM et al. 2011. Extraordinary neoteny of synaptic spines in the human prefrontal cortex. PNAS 108:3213281–86
    [Google Scholar]
  150. 150.
    Platt RJ, Zhou Y, Slaymaker IM, Shetty AS, Weisbach NR et al. 2017. Chd8 mutation leads to autistic-like behaviors and impaired striatal circuits. Cell Rep 19:2335–50
    [Google Scholar]
  151. 151.
    Pocklington AJ, Rees E, Walters JTR, Han J, Kavanagh DH et al. 2015. Novel findings from CNVs implicate inhibitory and excitatory signaling complexes in schizophrenia. Neuron 86:51203–14
    [Google Scholar]
  152. 152.
    Polepalli JS, Wu H, Goswami D, Halpern CH, Südhof TC, Malenka RC. 2017. Modulation of excitation on parvalbumin interneurons by neuroligin-3 regulates the hippocampal network. Nat. Neurosci. 20:219–29
    [Google Scholar]
  153. 153.
    Rannals MD, Hamersky GR, Page SC, Campbell MN, Briley A et al. 2016. Psychiatric risk gene Transcription Factor 4 regulates intrinsic excitability of prefrontal neurons via repression of SCN10a and KCNQ1. Neuron 90:143–55
    [Google Scholar]
  154. 154.
    Rapanelli M, Tan T, Wang W, Wang X, Wang Z-J et al. 2019. Behavioral, circuitry, and molecular aberrations by region-specific deficiency of the high-risk autism gene Cul3. Mol. Psychiatry 26:51491–504
    [Google Scholar]
  155. 155.
    Reynolds LM, Flores C. 2021. Mesocorticolimbic dopamine pathways across adolescence: diversity in development. Front. Neural Circuits 15:735625
    [Google Scholar]
  156. 156.
    Robertson CE, Ratai E-M, Kanwisher N. 2016. Reduced GABAergic action in the autistic brain. Curr. Biol. 26:180–85
    [Google Scholar]
  157. 157.
    Rodin RE, Dou Y, Kwon M, Sherman MA, D'Gama AM et al. 2021. The landscape of somatic mutation in cerebral cortex of autistic and neurotypical individuals revealed by ultra-deep whole-genome sequencing. Nat. Neurosci. 24:176–85
    [Google Scholar]
  158. 158.
    Rosenberg DR, Lewis DA. 1995. Postnatal maturation of the dopaminergic innervation of monkey prefrontal and motor cortices: a tyrosine hydroxylase immunohistochemical analysis. J. Comp. Neurol. 358:3383–400
    [Google Scholar]
  159. 159.
    Ross PJ, Zhang W-B, Mok RSF, Zaslavsky K, Deneault E et al. 2020. Synaptic dysfunction in human neurons with autism-associated deletions in PTCHD1-AS. Biol. Psychiatry 87:2139–49
    [Google Scholar]
  160. 160.
    Rothwell PE, Fuccillo MV, Maxeiner S, Hayton SJ, Gokce O et al. 2014. Autism-associated neuroligin-3 mutations commonly impair striatal circuits to boost repetitive behaviors. Cell 158:1198–212
    [Google Scholar]
  161. 161.
    Rubenstein JLR, Merzenich MM. 2003. Model of autism: increased ratio of excitation/inhibition in key neural systems. Genes Brain Behav 2:5255–67
    [Google Scholar]
  162. 162.
    Sadybekov A, Tian C, Arnesano C, Katritch V, Herring BE. 2017. An autism spectrum disorder-related de novo mutation hotspot discovered in the GEF1 domain of Trio. Nat. Commun. 8:1601
    [Google Scholar]
  163. 163.
    Sanders SJ, Campbell AJ, Cottrell JR, Moller RS, Wagner FF et al. 2018. Progress in understanding and treating SCN2A-mediated disorders. Trends Neurosci 41:7442–56
    [Google Scholar]
  164. 164.
    Sanders SJ, He X, Willsey AJ, Ercan-Sencicek AG, Samocha KE et al. 2015. Insights into autism spectrum disorder genomic architecture and biology from 71 risk loci. Neuron 87:61215–33
    [Google Scholar]
  165. 165.
    Sathyanesan A, Zhou J, Scafidi J, Heck DH, Sillitoe RV, Gallo V. 2019. Emerging connections between cerebellar development, behavior and complex brain disorders. Nat. Rev. Neurosci. 20:5298–313
    [Google Scholar]
  166. 166.
    Satterstrom FK, Kosmicki JA, Wang J, Breen MS, De Rubeis S et al. 2020. Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism. Cell 180:3568–84.e23
    [Google Scholar]
  167. 167.
    Schmack K, Bosc M, Ott T, Sturgill JF, Kepecs A. 2021. Striatal dopamine mediates hallucination-like perception in mice. Science 372:6537eabf4740
    [Google Scholar]
  168. 168.
    Schmitz N, Rubia K, van Amelsvoort T, Daly E, Smith A, Murphy DGM 2008. Neural correlates of reward in autism. Br. J. Psychiatry. 192:119–24
    [Google Scholar]
  169. 169.
    Schreiweis C, Bornschein U, Burguière E, Kerimoglu C, Schreiter S et al. 2014. Humanized Foxp2 accelerates learning by enhancing transitions from declarative to procedural performance. PNAS 111:3914253–58
    [Google Scholar]
  170. 170.
    Scott R, Sánchez-Aguilera A, van Elst K, Lim L, Dehorter N et al. 2019. Loss of Cntnap2 causes axonal excitability deficits, developmental delay in cortical myelination, and abnormal stereotyped motor behavior. Cereb. Cortex 29:2586–97
    [Google Scholar]
  171. 171.
    Sekar A, Bialas AR, de Rivera H, Davis A, Hammond TR et al. 2016. Schizophrenia risk from complex variation of complement component 4. Nature 530:7589177–83
    [Google Scholar]
  172. 172.
    Selimbeyoglu A, Kim CK, Inoue M, Lee SY, Hong ASO et al. 2017. Modulation of prefrontal cortex excitation/inhibition balance rescues social behavior in CNTNAP2-deficient mice. Sci. Transl. Med. 9:401eaah6733
    [Google Scholar]
  173. 173.
    Sell GL, Xin W, Cook EK, Zbinden MA, Schaffer TB et al. 2021. Deleting a UBE3A substrate rescues impaired hippocampal physiology and learning in Angelman syndrome mice. Sci. Rep. 11:119414
    [Google Scholar]
  174. 174.
    Sestan N, State MW. 2018. Lost in translation: traversing the complex path from genomics to therapeutics in autism spectrum disorder. Neuron 100:2406–23
    [Google Scholar]
  175. 175.
    Sharpe NA, Tepper JM. 1998. Postnatal development of excitatory synaptic input to the rat neostriatum: an electron microscopic study. Neuroscience 84:41163–75
    [Google Scholar]
  176. 176.
    Sholler DJ, Schoene L, Spindle TR. 2020. Therapeutic efficacy of cannabidiol (CBD): a review of the evidence from clinical trials and human laboratory studies. Curr. Addict. Rep. 7:3405–12
    [Google Scholar]
  177. 177.
    Shukla T, de la Peña JB, Perish JM, Ploski JE, Stumpf CR et al. 2021. A highly selective MNK inhibitor rescues deficits associated with fragile X syndrome in mice. Neurotherapeutics 18:1624–39
    [Google Scholar]
  178. 178.
    Silbereis JC, Pochareddy S, Zhu Y, Li M, Sestan N. 2016. The cellular and molecular landscapes of the developing human central nervous system. Neuron 89:2248–68
    [Google Scholar]
  179. 179.
    Singh T, Kurki MI, Curtis D, Purcell SM, Crooks L et al. 2016. Rare loss-of-function variants in SETD1A are associated with schizophrenia and developmental disorders. Nat. Neurosci. 19:4571–77
    [Google Scholar]
  180. 180.
    Singh T, Poterba T, Curtis D, Akil H, Al Eissa M et al. 2022. Rare coding variants in ten genes confer substantial risk for schizophrenia. Nature 604:509–16
    [Google Scholar]
  181. 181.
    Skirzewski M, Cronin ME, Murphy R, Fobbs W, Kravitz A, Buonanno A. 2020. ErbB4 null mice display altered mesocorticolimbic and nigrostriatal dopamine levels, as well as deficits in cognitive and motivational behaviors. eNeuro 7:3ENEURO.0395–19.2020
    [Google Scholar]
  182. 182.
    Slifstein M, van de Giessen E, Van Snellenberg J, Thompson JL, Narendran R et al. 2015. Deficits in prefrontal cortical and extrastriatal dopamine release in schizophrenia: a positron emission tomographic functional magnetic resonance imaging study. JAMA Psychiatry 72:4316–24
    [Google Scholar]
  183. 183.
    Sohal VS, Zhang F, Yizhar O, Deisseroth K. 2009. Parvalbumin neurons and gamma rhythms enhance cortical circuit performance. Nature 459:7247698–702
    [Google Scholar]
  184. 184.
    Spratt PWE, Ben-Shalom R, Keeshen CM, Burke KJ Jr., Clarkson RL et al. 2019. The autism-associated gene Scn2a contributes to dendritic excitability and synaptic function in the prefrontal cortex. Neuron 103:4673–85.e5
    [Google Scholar]
  185. 185.
    Srivastava S, Love-Nichols JA, Dies KA, Ledbetter DH, Martin CL et al. 2019. Meta-analysis and multidisciplinary consensus statement: Exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders. Genet. Med. 21:112413–21
    [Google Scholar]
  186. 186.
    Stephan AH, Barres BA, Stevens B. 2012. The complement system: an unexpected role in synaptic pruning during development and disease. Annu. Rev. Neurosci. 35:369–89
    [Google Scholar]
  187. 187.
    Sun Y, Paşca SP, Portmann T, Goold C, Worringer KA et al. 2016. A deleterious Nav1.1 mutation selectively impairs telencephalic inhibitory neurons derived from Dravet Syndrome patients. eLife 5:13073
    [Google Scholar]
  188. 188.
    Tabuchi K, Blundell J, Etherton MR, Hammer RE, Liu X et al. 2007. A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. Science 318:584771–76
    [Google Scholar]
  189. 189.
    Takata A, Xu B, Ionita-Laza I, Roos JL, Gogos JA, Karayiorgou M. 2014. Loss-of-function variants in schizophrenia risk and SETD1A as a candidate susceptibility gene. Neuron 82:4773–80
    [Google Scholar]
  190. 190.
    Tatavarty V, Torrado Pacheco A, Groves Kuhnle C, Lin H, Koundinya P et al. 2020. Autism-associated Shank3 is essential for homeostatic compensation in rodent V1. Neuron 106:769–77.e4
    [Google Scholar]
  191. 191.
    Tatsukawa T, Ogiwara I, Mazaki E, Shimohata A, Yamakawa K. 2018. Impairments in social novelty recognition and spatial memory in mice with conditional deletion of Scn1a in parvalbumin-expressing cells. Neurobiol. Dis. 112:24–34
    [Google Scholar]
  192. 192.
    Thelin J, Halje P, Nielsen J, Didriksen M, Petersson P, Bastlund JF. 2017. The translationally relevant mouse model of the 15q13.3 microdeletion syndrome reveals deficits in neuronal spike firing matching clinical neurophysiological biomarkers seen in schizophrenia. Acta Physiol 220:1124–36
    [Google Scholar]
  193. 193.
    Tian C, Paskus JD, Fingleton E, Roche KW, Herring BE. 2021. Autism spectrum disorder/intellectual disability-associated mutations in Trio disrupt neuroligin 1-mediated synaptogenesis. J. Neurosci. 41:377768–78
    [Google Scholar]
  194. 194.
    Tomchek SD, Dunn W. 2007. Sensory processing in children with and without autism: a comparative study using the short sensory profile. 612190–200
  195. 195.
    Toonen RFG, Wierda K, Sons MS, de Wit H, Cornelisse LN et al. 2006. Munc18-1 expression levels control synapse recovery by regulating readily releasable pool size. PNAS 103:4818332–37
    [Google Scholar]
  196. 196.
    Trubetskoy V, Pardiñas AF, Qi T, Panagiotaropoulou G, Awasthi S et al. 2022. Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nature 604:502–8
    [Google Scholar]
  197. 197.
    Uhlhaas PJ, Singer W. 2010. Abnormal neural oscillations and synchrony in schizophrenia. Nat. Rev. Neurosci. 11:2100–13
    [Google Scholar]
  198. 198.
    Verhage M, Sørensen JB. 2020. SNAREopathies: diversity in mechanisms and symptoms. Neuron 107:122–37
    [Google Scholar]
  199. 199.
    Vissers LELM, Gilissen C, Veltman JA. 2016. Genetic studies in intellectual disability and related disorders. Nat. Rev. Genet. 17:19–18
    [Google Scholar]
  200. 200.
    Vogt D, Cho KKA, Shelton SM, Paul A, Huang ZJ et al. 2018. Mouse Cntnap2 and human CNTNAP2 ASD alleles cell autonomously regulate PV+ cortical interneurons. Cereb. Cortex. 28:113868–79
    [Google Scholar]
  201. 201.
    Volk L, Chiu S-L, Sharma K, Huganir RL. 2015. Glutamate synapses in human cognitive disorders. Annu. Rev. Neurosci. 38:127–49
    [Google Scholar]
  202. 202.
    Wallace ML, Burette AC, Weinberg RJ, Philpot BD. 2012. Maternal loss of Ube3a produces an excitatory/inhibitory imbalance through neuron type-specific synaptic defects. Neuron 74:5793–800
    [Google Scholar]
  203. 203.
    Walsh T, McClellan JM, McCarthy SE, Addington AM, Pierce SB et al. 2008. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 320:5875539–43
    [Google Scholar]
  204. 204.
    Wang C-C, Held RG, Chang S-C, Yang L, Delpire E et al. 2011. A critical role for GluN2B-containing NMDA receptors in cortical development and function. Neuron 72:5789–805
    [Google Scholar]
  205. 205.
    Wang M, Gallo NB, Tai Y, Li B, Van Aelst L. 2021. Oligophrenin-1 moderates behavioral responses to stress by regulating parvalbumin interneuron activity in the medial prefrontal cortex. Neuron 109:1636–56.e8
    [Google Scholar]
  206. 206.
    Wang W, Li C, Chen Q, van der Goes M-S, Hawrot J et al. 2017. Striatopallidal dysfunction underlies repetitive behavior in Shank3-deficient model of autism. J. Clin. Invest. 127:51978–90
    [Google Scholar]
  207. 207.
    Wells MF, Wimmer RD, Schmitt LI, Feng G, Halassa MM. 2016. Thalamic reticular impairment underlies attention deficit in Ptchd1Y/− mice. Nature 532:759758–63
    [Google Scholar]
  208. 208.
    Wen L, Lu Y-S, Zhu X-H, Li X-M, Woo R-S et al. 2010. Neuregulin 1 regulates pyramidal neuron activity via ErbB4 in parvalbumin-positive interneurons. PNAS 107:31211–16
    [Google Scholar]
  209. 209.
    Wilkinson CL, Levin AR, Gabard-Durnam LJ, Tager-Flusberg H, Nelson CA. 2019. Reduced frontal gamma power at 24 months is associated with better expressive language in toddlers at risk for autism. Autism Res 12:81211–24
    [Google Scholar]
  210. 210.
    Willsey HR, Willsey AJ, Wang B, State MW 2022. Genomics, convergent neuroscience and progress in understanding autism spectrum disorder. Nat. Rev. Neurosci. 23:323–41
    [Google Scholar]
  211. 211.
    Winton-Brown T, Schmidt A, Roiser JP, Howes OD, Egerton A et al. 2017. Altered activation and connectivity in a hippocampal–basal ganglia–midbrain circuit during salience processing in subjects at ultra high risk for psychosis. Transl. Psychiatry 7:10e1245
    [Google Scholar]
  212. 212.
    Woo TU, Whitehead RE, Melchitzky DS, Lewis DA. 1998. A subclass of prefrontal γ-aminobutyric acid axon terminals are selectively altered in schizophrenia. PNAS 95:95341–46
    [Google Scholar]
  213. 213.
    Xu X, Miller EC, Pozzo-Miller L. 2014. Dendritic spine dysgenesis in Rett syndrome. Front. Neuroanat. 8:97
    [Google Scholar]
  214. 214.
    Yamamoto J, Suh J, Takeuchi D, Tonegawa S. 2014. Successful execution of working memory linked to synchronized high-frequency gamma oscillations. Cell 157:4845–57
    [Google Scholar]
  215. 215.
    Yi JJ, Berrios J, Newbern JM, Snider WD, Philpot BD et al. 2015. An autism-linked mutation disables phosphorylation control of UBE3A. Cell 162:4795–807
    [Google Scholar]
  216. 216.
    Yilmaz M, Yalcin E, Presumey J, Aw E, Ma M et al. 2021. Overexpression of schizophrenia susceptibility factor human complement C4A promotes excessive synaptic loss and behavioral changes in mice. Nat. Neurosci. 24:214–24
    [Google Scholar]
  217. 217.
    Yoshida T, Yasumura M, Uemura T, Lee S-J, Ra M et al. 2011. IL-1 receptor accessory protein-like 1 associated with mental retardation and autism mediates synapse formation by trans-synaptic interaction with protein tyrosine phosphatase δ. J. Neurosci. 31:3813485–99
    [Google Scholar]
  218. 218.
    Zoghbi HY, Bear MF. 2012. Synaptic dysfunction in neurodevelopmental disorders associated with autism and intellectual disabilities. Cold Spring Harb. Perspect. Biol. 4:3a009886
    [Google Scholar]
/content/journals/10.1146/annurev-genet-072820-023642
Loading
/content/journals/10.1146/annurev-genet-072820-023642
Loading

Data & Media loading...

Supplementary Data

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error