{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:18:37Z","timestamp":1791353917778,"version":"4.3.1"},"reference-count":118,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["R01MH124992 R01MH119149"],"award-info":[{"award-number":["R01MH124992 R01MH119149"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>As the main secondary messengers, cyclic AMP (cAMP) and Ca<jats:sup>2+<\/jats:sup> trigger intracellular signal transduction cascade and, in turn, regulate many aspects of cellular function in developing and mature neurons. The group I adenylyl cyclase (ADCY, also known as AC) isoforms, including ADCY1, 3, and 8 (also known as AC1, AC3, and AC8), are stimulated by Ca<jats:sup>2+<\/jats:sup> and thus functionally positioned to integrate cAMP and Ca<jats:sup>2+<\/jats:sup> signaling. Emerging lines of evidence have suggested the association of the Ca<jats:sup>2+<\/jats:sup>-stimulated ADCYs with bipolar disorder, schizophrenia, major depressive disorder, post-traumatic stress disorder, and autism. In this review, we discuss the molecular and cellular features as well as the physiological functions of ADCY1, 3, and 8. We further discuss the recent therapeutic development to target the Ca<jats:sup>2+<\/jats:sup>-stimulated ADCYs for potential treatments of psychiatric and neurodevelopmental disorders.<\/jats:p>","DOI":"10.3389\/fphar.2022.949384","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T07:59:53Z","timestamp":1663315193000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Ca2+-stimulated adenylyl cyclases as therapeutic targets for psychiatric and neurodevelopmental disorders"],"prefix":"10.3389","volume":"13","author":[{"given":"Jiao","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.biopsych.2008.01.003","article-title":"The role of the cerebellum in schizophrenia","volume":"64","author":"Andreasen","year":"2008","journal-title":"Biol. Psychiatry"},{"key":"B2","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1038\/nature11737","article-title":"FMRP targets distinct mRNA sequence elements to regulate protein expression","volume":"492","author":"Ascano","year":"2012","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1038\/sj.mp.4001388","article-title":"Linkage of bipolar affective disorder on chromosome 8q24: Follow-up and parametric analysis","volume":"9","author":"Avramopoulos","year":"2004","journal-title":"Mol. Psychiatry"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1126\/science.2255909","article-title":"Identification of a specialized adenylyl cyclase that may mediate odorant detection","volume":"250","author":"Bakalyar","year":"1990","journal-title":"Science"},{"key":"B5","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1038\/nrm1155","article-title":"Calcium signalling: Dynamics, homeostasis and remodelling","volume":"4","author":"Berridge","year":"2003","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1002\/cne.21510","article-title":"Type III adenylyl cyclase localizes to primary cilia throughout the adult mouse brain","volume":"505","author":"Bishop","year":"2007","journal-title":"J. Comp. Neurol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/s0092-8674(01)00568-2","article-title":"Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome","volume":"107","author":"Brown","year":"2001","journal-title":"Cell"},{"key":"B8","doi-asserted-by":"publisher","first-page":"eaah5381","DOI":"10.1126\/scisignal.aah5381","article-title":"Identification of a selective small-molecule inhibitor of type 1 adenylyl cyclase activity with analgesic properties","volume":"10","author":"Brust","year":"2017","journal-title":"Sci. Signal."},{"key":"B9","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1073\/pnas.96.1.79","article-title":"Cytosolic adenylyl cyclase defines a unique signaling molecule in mammals","volume":"96","author":"Buck","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B10","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1002\/ajmg.b.32391","article-title":"Currently recognized genes for schizophrenia: High-resolution chromosome ideogram representation","author":"Butler","year":"","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet."},{"key":"B11","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.gene.2015.08.057","article-title":"Currently recognized clinically relevant and known genes for human reproduction and related infertility with representation on high-resolution chromosome ideograms","volume":"575","author":"Butler","year":"","journal-title":"Gene"},{"key":"B12","doi-asserted-by":"publisher","first-page":"12190","DOI":"10.1016\/s0021-9258(17)32700-x","article-title":"Type VIII adenylyl cyclase. A Ca2+\/calmodulin-stimulated enzyme expressed in discrete regions of rat brain","volume":"269","author":"Cali","year":"1994","journal-title":"J. Biol. Chem."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e122","DOI":"10.3399\/bjgp14X677482","article-title":"Prevalence of comorbid depression and obesity in general practice: A cross-sectional survey","volume":"64","author":"Carey","year":"2014","journal-title":"Br. J. Gen. Pract."},{"key":"B14","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1523\/JNEUROSCI.2478-14.2015","article-title":"Overexpression of the type 1 adenylyl cyclase in the forebrain leads to deficits of behavioral inhibition","volume":"35","author":"Chen","year":"2015","journal-title":"J. Neurosci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1016\/j.biopsych.2015.12.012","article-title":"Ablation of type III adenylyl cyclase in mice causes reduced neuronal activity, altered sleep pattern, and depression-like phenotypes","volume":"80","author":"Chen","year":"2016","journal-title":"Biol. Psychiatry"},{"key":"B16","doi-asserted-by":"publisher","first-page":"6492","DOI":"10.1021\/bi00143a019","article-title":"Stimulation of the type III olfactory adenylyl cyclase by calcium and calmodulin","volume":"31","author":"Choi","year":"1992","journal-title":"Biochemistry"},{"key":"B17","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1016\/j.neuroscience.2007.01.045","article-title":"Distinct regional and subcellular localization of adenylyl cyclases type 1 and 8 in mouse brain","volume":"146","author":"Conti","year":"2007","journal-title":"Neuroscience"},{"key":"B18","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1042\/BJ20031061","article-title":"Regulation and organization of adenylyl cyclases and cAMP","volume":"375","author":"Cooper","year":"2003","journal-title":"Biochem. J."},{"key":"B19","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.cell.2011.06.013","article-title":"FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism","volume":"146","author":"Darnell","year":"2011","journal-title":"Cell"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1016\/j.biopsych.2009.06.016","article-title":"Interspecies trait genetics reveals association of Adcy8 with mouse avoidance behavior and a human mood disorder","volume":"66","author":"de Mooij-van Malsen","year":"2009","journal-title":"Biol. Psychiatry"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1562","DOI":"10.1002\/cne.23000","article-title":"Role of adenylate cyclase 1 in retinofugal map development","volume":"520","author":"Dhande","year":"2012","journal-title":"J. Comp. Neurol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"E9327","DOI":"10.3390\/ijms21239327","article-title":"Carbamazepine restores neuronal signaling, protein synthesis, and cognitive function in a mouse model of fragile X syndrome","volume":"21","author":"Ding","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2393","DOI":"10.1523\/JNEUROSCI.4356-08.2009","article-title":"A role for calmodulin-stimulated adenylyl cyclases in cocaine sensitization","volume":"29","author":"DiRocco","year":"2009","journal-title":"J. Neurosci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.schres.2016.08.007","article-title":"Postmortem structural studies of the thalamus in schizophrenia","volume":"180","author":"Dorph-Petersen","year":"2017","journal-title":"Schizophr. Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1038\/nn.2174","article-title":"Circadian oscillation of hippocampal MAPK activity and cAmp: Implications for memory persistence","volume":"11","author":"Eckel-Mahan","year":"2008","journal-title":"Nat. Neurosci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"12438","DOI":"10.1074\/jbc.271.21.12438","article-title":"Functional co-localization of transfected Ca(2+)-stimulable adenylyl cyclases with capacitative Ca2+ entry sites","volume":"271","author":"Fagan","year":"1996","journal-title":"J. Biol. Chem."},{"key":"B27","doi-asserted-by":"publisher","first-page":"4859","DOI":"10.1523\/JNEUROSCI.5407-03.2004","article-title":"Extracellular signal-regulated protein kinase activation is required for metabotropic glutamate receptor-dependent long-term depression in hippocampal area CA1","volume":"24","author":"Gallagher","year":"2004","journal-title":"J. Neurosci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1038\/nrn.2016.57","article-title":"Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression","volume":"17","author":"Grace","year":"2016","journal-title":"Nat. Rev. Neurosci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1038\/s41588-017-0022-7","article-title":"Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes","volume":"50","author":"Grarup","year":"2018","journal-title":"Nat. Genet."},{"key":"B30","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1038\/npp.2013.203","article-title":"Neuronal primary cilia: An underappreciated signaling and sensory organelle in the brain","volume":"39","author":"Green","year":"2014","journal-title":"Neuropsychopharmacology"},{"key":"B31","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1038\/s41386-018-0150-5","article-title":"Isoform-selective phosphoinositide 3-kinase inhibition ameliorates a broad range of fragile X syndrome-associated deficits in a mouse model","volume":"44","author":"Gross","year":"2019","journal-title":"Neuropsychopharmacology"},{"key":"B32","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/j.celrep.2015.03.060","article-title":"Increased expression of the PI3K enhancer PIKE mediates deficits in synaptic plasticity and behavior in fragile X syndrome","volume":"11","author":"Gross","year":"2015","journal-title":"Cell Rep."},{"key":"B33","doi-asserted-by":"publisher","first-page":"193","DOI":"10.3109\/15622970109026809","article-title":"Obsessive compulsive behaviour in autism--towards an autistic-obsessive compulsive syndrome?","volume":"2","author":"Gross-Isseroff","year":"2001","journal-title":"World J. Biol. Psychiatry"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2626","DOI":"10.1523\/JNEUROSCI.2906-12.2013","article-title":"Arborization of dendrites by developing neocortical neurons is dependent on primary cilia and type 3 adenylyl cyclase","volume":"33","author":"Guadiana","year":"2013","journal-title":"J. Neurosci."},{"key":"B35","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1038\/s41398-019-0488-4","article-title":"Commonality in dysregulated expression of gene sets in cortical brains of individuals with autism, schizophrenia, and bipolar disorder","volume":"9","author":"Guan","year":"2019","journal-title":"Transl. Psychiatry"},{"key":"B36","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1016\/j.biopsych.2005.05.040","article-title":"Trait markers of alcohol, U., and dependence, IPlatelet adenylyl cyclase activity: A biological marker for major depression and recent drug use","volume":"58","author":"Hines","year":"2005","journal-title":"Biol. Psychiatry"},{"key":"B37","doi-asserted-by":"publisher","first-page":"48108","DOI":"10.1074\/jbc.M106388200","article-title":"Characterization of the mechanism underlying the reversal of long term potentiation by low frequency stimulation at hippocampal CA1 synapses","volume":"276","author":"Huang","year":"2001","journal-title":"J. Biol. Chem."},{"key":"B38","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1001\/jamapsychiatry.2017.3433","article-title":"Association of polygenic score for schizophrenia and hla antigen and inflammation genes with response to lithium in bipolar affective disorder: A genome-wide association study","volume":"75","author":"International Consortium on Lithium Genetics.","year":"2018","journal-title":"JAMA Psychiatry"},{"key":"B39","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1080\/0953710021000062905","article-title":"Molecular and biochemical evidence for the presence of type III adenylyl cyclase in human platelets","volume":"14","author":"Katsel","year":"2003","journal-title":"Platelets"},{"key":"B40","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1016\/j.ejmech.2018.11.036","article-title":"Optimization of a 1, 3, 4-oxadiazole series for inhibition of Ca(2+)\/calmodulin-stimulated activity of adenylyl cyclases 1 and 8 for the treatment of chronic pain","volume":"162","author":"Kaur","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"B41","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/s0092-8674(04)00115-1","article-title":"Translational control by MAPK signaling in long-term synaptic plasticity and memory","volume":"116","author":"Kelleher","year":"2004","journal-title":"Cell"},{"key":"B42","doi-asserted-by":"publisher","first-page":"3727","DOI":"10.1073\/pnas.1322778111","article-title":"Crystal structures of human soluble adenylyl cyclase reveal mechanisms of catalysis and of its activation through bicarbonate","volume":"111","author":"Kleinboelting","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B43","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1093\/chemse\/bjw061","article-title":"The association between olfaction and depression: A systematic review","volume":"41","author":"Kohli","year":"2016","journal-title":"Chem. Senses"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1558","DOI":"10.1126\/science.2472670","article-title":"Adenylyl cyclase amino acid sequence: Possible channel- or transporter-like structure","volume":"244","author":"Krupinski","year":"1989","journal-title":"Science"},{"key":"B45","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1038\/35016089","article-title":"Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity","volume":"405","author":"Lee","year":"2000","journal-title":"Nature"},{"key":"B46","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/bs.apcsb.2015.10.004","article-title":"AMPA receptors as therapeutic targets for neurological disorders","volume":"103","author":"Lee","year":"2016","journal-title":"Adv. Protein Chem. Struct. Biol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1007\/s13311-020-00927-1","article-title":"Neuronal adenylyl cyclase targeting central plasticity for the treatment of chronic pain","volume":"17","author":"Li","year":"2020","journal-title":"Neurotherapeutics"},{"key":"B48","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1152\/jn.01205.2004","article-title":"Calcium-stimulated adenylyl cyclases required for long-term potentiation in the anterior cingulate cortex","volume":"94","author":"Liauw","year":"2005","journal-title":"J. Neurophysiol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"15922","DOI":"10.1074\/jbc.M212475200","article-title":"Kinetic properties of \"soluble\" adenylyl cyclase. Synergism between calcium and bicarbonate","volume":"278","author":"Litvin","year":"2003","journal-title":"J. Biol. Chem."},{"key":"B50","doi-asserted-by":"publisher","first-page":"BSR20191942","DOI":"10.1042\/BSR20191942","article-title":"Integrative analysis of shared genetic pathogenesis by autism spectrum disorder and obsessive-compulsive disorder","volume":"39","author":"Liu","year":"2019","journal-title":"Biosci. Rep."},{"key":"B51","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.jad.2020.02.041","article-title":"Type 3 adenylyl cyclase in the main olfactory epithelium participates in depression-like and anxiety-like behaviours","volume":"268","author":"Liu","year":"","journal-title":"J. Affect. Disord."},{"key":"B52","doi-asserted-by":"publisher","first-page":"112533","DOI":"10.1016\/j.bbr.2020.112533","article-title":"Type 3 adenylyl cyclase in the MOE is involved in learning and memory in mice","volume":"383","author":"Liu","year":"","journal-title":"Behav. Brain Res."},{"key":"B53","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1038\/nn1106","article-title":"Adenylyl cyclase I regulates AMPA receptor trafficking during mouse cortical 'barrel' map development","volume":"6","author":"Lu","year":"2003","journal-title":"Nat. Neurosci."},{"key":"B54","doi-asserted-by":"publisher","first-page":"2500","DOI":"10.1523\/jneurosci.19-07-02500.1999","article-title":"Adenylyl cyclase activation modulates activity-dependent changes in synaptic strength and Ca2+\/calmodulin-dependent kinase II autophosphorylation","volume":"19","author":"Makhinson","year":"1999","journal-title":"J. Neurosci."},{"key":"B55","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1098\/rstb.2002.1233","article-title":"AMPA receptor trafficking and long-term potentiation","volume":"358","author":"Malinow","year":"2003","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"B56","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1111\/j.1399-5618.2009.00762.x","article-title":"Inhibition of specific adenylyl cyclase isoforms by lithium and carbamazepine, but not valproate, may be related to their antidepressant effect","volume":"11","author":"Mann","year":"2009","journal-title":"Bipolar Disord."},{"key":"B57","doi-asserted-by":"publisher","first-page":"e0157240","DOI":"10.1371\/journal.pone.0157240","article-title":"Prospective associations between depression and obesity for adolescent males and females- A systematic review and meta-analysis of longitudinal studies","volume":"11","author":"Mannan","year":"2016","journal-title":"PLoS One"},{"key":"B58","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1124\/mol.108.051748","article-title":"Capacitative Ca2+ entry via Orai1 and stromal interacting molecule 1 (STIM1) regulates adenylyl cyclase type 8","volume":"75","author":"Martin","year":"2009","journal-title":"Mol. Pharmacol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1744806919842961","DOI":"10.1177\/1744806919842961","article-title":"Calcium-stimulated adenylyl cyclase subtype 1 is required for presynaptic long-term potentiation in the insular cortex of adult mice","volume":"15","author":"Miao","year":"2019","journal-title":"Mol. Pain"},{"key":"B60","doi-asserted-by":"publisher","first-page":"2051","DOI":"10.1523\/jneurosci.19-06-02051.1999","article-title":"The 5'-flanking region of the mouse adenylyl cyclase type VIII gene imparts tissue-specific expression in transgenic mice","volume":"19","author":"Muglia","year":"1999","journal-title":"J. Neurosci."},{"key":"B61","doi-asserted-by":"publisher","first-page":"107426","DOI":"10.1016\/j.pharmthera.2019.107426","article-title":"The origin of NMDA receptor hypofunction in schizophrenia","volume":"205","author":"Nakazawa","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"B62","doi-asserted-by":"publisher","first-page":"33308","DOI":"10.1074\/jbc.271.52.33308","article-title":"Differential regulation of type I and type VIII Ca2+-stimulated adenylyl cyclases by Gi-coupled receptors in vivo","volume":"271","author":"Nielsen","year":"1996","journal-title":"J. Biol. Chem."},{"key":"B63","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/sj.mp.4000795","article-title":"Protein kinase A and Rap1 levels in platelets of untreated patients with major depression","volume":"6","author":"Perez","year":"2001","journal-title":"Mol. Psychiatry"},{"key":"B64","doi-asserted-by":"publisher","first-page":"e110226","DOI":"10.1371\/journal.pone.0110226","article-title":"A gain-of-function mutation in adenylate cyclase 3 protects mice from diet-induced obesity","volume":"9","author":"Pitman","year":"2014","journal-title":"PLoS One"},{"key":"B65","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/j.neuroscience.2010.07.022","article-title":"Functional role of calcium-stimulated adenylyl cyclase 8 in adaptations to psychological stressors in the mouse: Implications for mood disorders","volume":"170","author":"Razzoli","year":"2010","journal-title":"Neuroscience"},{"key":"B66","doi-asserted-by":"publisher","first-page":"e442","DOI":"10.1038\/tp.2014.66","article-title":"Blood transcriptomic biomarkers in adult primary care patients with major depressive disorder undergoing cognitive behavioral therapy","volume":"4","author":"Redei","year":"2014","journal-title":"Transl. Psychiatry"},{"key":"B67","doi-asserted-by":"publisher","first-page":"R870","DOI":"10.1152\/ajpregu.00374.2001","article-title":"Activation of adenylyl cyclases, regulation of insulin status, and cell survival by G(alpha)olf in pancreatic beta-cells","volume":"282","author":"Regnauld","year":"2002","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/s41583-021-00432-0","article-title":"The molecular biology of FMRP: New insights into fragile X syndrome","volume":"22","author":"Richter","year":"2021","journal-title":"Nat. Rev. Neurosci."},{"key":"B69","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1016\/j.tins.2014.07.001","article-title":"Emerging role of CaMKII in neuropsychiatric disease","volume":"37","author":"Robison","year":"2014","journal-title":"Trends Neurosci."},{"key":"B70","doi-asserted-by":"publisher","first-page":"4809","DOI":"10.1523\/jneurosci.20-13-04809.2000","article-title":"Altered stress-induced anxiety in adenylyl cyclase type VIII-deficient mice","volume":"20","author":"Schaefer","year":"2000","journal-title":"J. Neurosci."},{"key":"B71","doi-asserted-by":"publisher","first-page":"4667","DOI":"10.1021\/acs.jmedchem.1c01759","article-title":"Optimization of a pyrimidinone series for selective inhibition of Ca(2+)\/calmodulin-stimulated adenylyl cyclase 1 activity for the treatment of chronic pain","volume":"65","author":"Scott","year":"2022","journal-title":"J. Med. Chem."},{"key":"B72","doi-asserted-by":"publisher","first-page":"14359","DOI":"10.1038\/ncomms14359","article-title":"Enhanced expression of ADCY1 underlies aberrant neuronal signalling and behaviour in a syndromic autism model","volume":"8","author":"Sethna","year":"2017","journal-title":"Nat. Commun."},{"key":"B73","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1007\/s11064-013-1229-3","article-title":"From FMRP function to potential therapies for fragile X syndrome","volume":"39","author":"Sethna","year":"2014","journal-title":"Neurochem. Res."},{"key":"B74","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1038\/s41588-017-0020-9","article-title":"Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity","volume":"50","author":"Siljee","year":"2018","journal-title":"Nat. Genet."},{"key":"B75","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.neuron.2006.11.024","article-title":"Ca2+ -stimulated adenylyl cyclases regulate ERK-dependent activation of MSK1 during fear conditioning","volume":"53","author":"Sindreu","year":"2007","journal-title":"Neuron"},{"key":"B76","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1016\/0166-2236(88)90199-3","article-title":"Calcium ions, active zones and synaptic transmitter release","volume":"11","author":"Smith","year":"1988","journal-title":"Trends Neurosci."},{"key":"B77","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1016\/s0896-6273(00)80500-0","article-title":"Impaired cerebellar long-term potentiation in type I adenylyl cyclase mutant mice","volume":"20","author":"Storm","year":"1998","journal-title":"Neuron"},{"key":"B78","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.gene.2017.10.035","article-title":"Functional analysis of schizophrenia genes using GeneAnalytics program and integrated databases","volume":"641","author":"Sundararajan","year":"2018","journal-title":"Gene"},{"key":"B79","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1016\/j.neuroscience.2015.01.043","article-title":"Thalamic adenylyl cyclase 1 is required for barrel formation in the somatosensory cortex","volume":"290","author":"Suzuki","year":"2015","journal-title":"Neuroscience"},{"key":"B80","doi-asserted-by":"publisher","first-page":"8595","DOI":"10.1016\/s0021-9258(18)93016-4","article-title":"Expression and characterization of calmodulin-activated (type I) adenylylcyclase","volume":"266","author":"Tang","year":"1991","journal-title":"J. Biol. Chem."},{"key":"B81","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1007\/s10567-011-0097-0","article-title":"Anxiety disorders in children and adolescents with autistic spectrum disorders: A meta-analysis","volume":"14","author":"van Steensel","year":"2011","journal-title":"Clin. Child. Fam. Psychol. Rev."},{"key":"B82","doi-asserted-by":"publisher","first-page":"3186","DOI":"10.1523\/jneurosci.18-09-03186.1998","article-title":"Type I adenylyl cyclase mutant mice have impaired mossy fiber long-term potentiation","volume":"18","author":"Villacres","year":"1998","journal-title":"J. Neurosci."},{"key":"B83","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1046\/j.1471-4159.2002.01206.x","article-title":"Synaptic concentration of type-I adenylyl cyclase in cerebellar neurons","volume":"83","author":"Wang","year":"2002","journal-title":"J. Neurochem."},{"key":"B84","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1038\/nn1248","article-title":"Overexpression of type-1 adenylyl cyclase in mouse forebrain enhances recognition memory and LTP","volume":"7","author":"Wang","year":"2004","journal-title":"Nat. Neurosci."},{"key":"B85","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1074\/jbc.M607291200","article-title":"Genetic evidence for adenylyl cyclase 1 as a target for preventing neuronal excitotoxicity mediated by N-methyl-D-aspartate receptors","volume":"282","author":"Wang","year":"2007","journal-title":"J. Biol. Chem."},{"key":"B86","doi-asserted-by":"publisher","first-page":"9710","DOI":"10.1523\/jneurosci.23-30-09710.2003","article-title":"Type 8 adenylyl cyclase is targeted to excitatory synapses and required for mossy fiber long-term potentiation","volume":"23","author":"Wang","year":"2003","journal-title":"J. Neurosci."},{"key":"B87","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1124\/mol.63.3.463","article-title":"Calmodulin-regulated adenylyl cyclases: Cross-talk and plasticity in the central nervous system","volume":"63","author":"Wang","year":"2003","journal-title":"Mol. Pharmacol."},{"key":"B88","doi-asserted-by":"publisher","first-page":"65ra3","DOI":"10.1126\/scitranslmed.3001269","article-title":"Identification of an adenylyl cyclase inhibitor for treating neuropathic and inflammatory pain","volume":"3","author":"Wang","year":"","journal-title":"Sci. Transl. Med."},{"key":"B89","doi-asserted-by":"publisher","first-page":"17448069221089596","DOI":"10.1177\/17448069221089596","article-title":"Human safety study of a selective neuronal adenylate cyclase 1 inhibitor NB001 which relieves the neuropathic pain and blocks ACC in adult mice.","volume":"2022","author":"Wang","year":"2022","journal-title":"Mol. Pain"},{"key":"B90","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1111\/j.1471-4159.2012.07722.x","article-title":"Activation of the extracellular signal-regulated kinase pathway contributes to the behavioral deficit of fragile x-syndrome","volume":"121","author":"Wang","year":"2012","journal-title":"J. Neurochem."},{"key":"B91","doi-asserted-by":"publisher","first-page":"e6979","DOI":"10.1371\/journal.pone.0006979","article-title":"Adult type 3 adenylyl cyclase-deficient mice are obese","volume":"4","author":"Wang","year":"2009","journal-title":"PLoS One"},{"key":"B92","doi-asserted-by":"publisher","first-page":"5557","DOI":"10.1523\/JNEUROSCI.6561-10.2011","article-title":"The type 3 adenylyl cyclase is required for novel object learning and extinction of contextual memory: Role of cAMP signaling in primary cilia","volume":"31","author":"Wang","year":"","journal-title":"J. Neurosci."},{"key":"B93","doi-asserted-by":"publisher","first-page":"21480","DOI":"10.1074\/jbc.270.37.21480","article-title":"Ca2+ inhibition of type III adenylyl cyclase in vivo","volume":"270","author":"Wayman","year":"1995","journal-title":"J. Biol. Chem."},{"key":"B94","doi-asserted-by":"publisher","first-page":"25400","DOI":"10.1016\/s0021-9258(18)47263-8","article-title":"Synergistic activation of the type I adenylyl cyclase by Ca2+ and Gs-coupled receptors in vivo","volume":"269","author":"Wayman","year":"1994","journal-title":"J. Biol. Chem."},{"key":"B95","doi-asserted-by":"publisher","first-page":"6075","DOI":"10.1128\/MCB.16.11.6075","article-title":"Regulation of type I adenylyl cyclase by calmodulin kinase IV in vivo","volume":"16","author":"Wayman","year":"1996","journal-title":"Mol. Cell. Biol."},{"key":"B96","doi-asserted-by":"publisher","first-page":"24231","DOI":"10.1074\/jbc.271.39.24231","article-title":"Phosphorylation and inhibition of type III adenylyl cyclase by calmodulin-dependent protein kinase II in vivo","volume":"271","author":"Wei","year":"1996","journal-title":"J. Biol. Chem."},{"key":"B97","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/s0896-6273(00)80561-9","article-title":"Phosphorylation and inhibition of olfactory adenylyl cyclase by CaM kinase II in neurons: A mechanism for attenuation of olfactory signals","volume":"21","author":"Wei","year":"1998","journal-title":"Neuron"},{"key":"B98","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1002\/da.22260","article-title":"A genome-wide association study of clinical symptoms of dissociation in a trauma-exposed sample","volume":"31","author":"Wolf","year":"2014","journal-title":"Depress. Anxiety"},{"key":"B99","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1016\/s0896-6273(01)80036-2","article-title":"Calcium-stimulated adenylyl cyclase activity is critical for hippocampus-dependent long-term memory and late phase LTP","volume":"23","author":"Wong","year":"1999","journal-title":"Neuron"},{"key":"B100","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/s0896-6273(00)00060-x","article-title":"Disruption of the type III adenylyl cyclase gene leads to peripheral and behavioral anosmia in transgenic mice","volume":"27","author":"Wong","year":"2000","journal-title":"Neuron"},{"key":"B101","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1038\/mp.2010.109","article-title":"Genome-wide association study of major depressive disorder: New results, meta-analysis, and lessons learned","volume":"17","author":"Wray","year":"2012","journal-title":"Mol. Psychiatry"},{"key":"B102","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1093\/schbul\/sbw102","article-title":"Szdb: A database for schizophrenia genetic research","volume":"43","author":"Wu","year":"2017","journal-title":"Schizophr. Bull."},{"key":"B103","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1073\/pnas.92.1.220","article-title":"Altered behavior and long-term potentiation in type I adenylyl cyclase mutant mice","volume":"92","author":"Wu","year":"1995","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B104","doi-asserted-by":"publisher","first-page":"23766","DOI":"10.1016\/s0021-9258(20)80447-5","article-title":"Modification of the calcium and calmodulin sensitivity of the type I adenylyl cyclase by mutagenesis of its calmodulin binding domain","volume":"268","author":"Wu","year":"1993","journal-title":"J. Biol. Chem."},{"key":"B105","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1111\/j.1471-4159.1993.tb05852.x","article-title":"Type I calmodulin-sensitive adenylyl cyclase is neural specific","volume":"60","author":"Xia","year":"1993","journal-title":"J. Neurochem."},{"key":"B106","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/0304-3940(92)90742-p","article-title":"The type III calcium\/calmodulin-sensitive adenylyl cyclase is not specific to olfactory sensory neurons","volume":"144","author":"Xia","year":"1992","journal-title":"Neurosci. Lett."},{"key":"B107","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1006\/bbrc.1998.9983","article-title":"Molecular cloning of a full-length cDNA for human type 3 adenylyl cyclase and its expression in human islets","volume":"254","author":"Yang","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B108","doi-asserted-by":"publisher","first-page":"e2102568","DOI":"10.1002\/advs.202102568","article-title":"Ciliary type III adenylyl cyclase in the VMH is crucial for high-fat diet-induced obesity mediated by autophagy","volume":"9","author":"Yang","year":"2022","journal-title":"Adv. Sci."},{"key":"B109","doi-asserted-by":"publisher","first-page":"100237","DOI":"10.1016\/j.ynstr.2020.100237","article-title":"Forebrain overexpression of type 1 adenylyl cyclase promotes molecular stability and behavioral resilience to physical stress","volume":"13","author":"Yang","year":"2020","journal-title":"Neurobiol. Stress"},{"key":"B110","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/nature13992","article-title":"A comparative encyclopedia of DNA elements in the mouse genome","volume":"515","author":"Yue","year":"2014","journal-title":"Nature"},{"key":"B111","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1002\/ajmg.b.30651","article-title":"Family-based SNP association study on 8q24 in bipolar disorder","author":"Zandi","year":"2008","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet."},{"key":"B112","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1038\/mp.2017.255","article-title":"Mechanisms of ketamine action as an antidepressant","volume":"23","author":"Zanos","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"B113","doi-asserted-by":"publisher","first-page":"600758","DOI":"10.3389\/fncel.2020.600758","article-title":"Store-operated calcium channels in physiological and pathological States of the nervous system","volume":"14","author":"Zhang","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"B114","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1111\/j.1399-5618.2010.00883.x","article-title":"Family-based association analysis to finemap bipolar linkage peak on chromosome 8q24 using 2, 500 genotyped SNPs and 15, 000 imputed SNPs","volume":"12","author":"Zhang","year":"2010","journal-title":"Bipolar Disord."},{"key":"B115","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1101\/lm.040642.115","article-title":"Voluntary running depreciates the requirement of Ca2+-stimulated cAMP signaling in synaptic potentiation and memory formation","volume":"23","author":"Zheng","year":"2016","journal-title":"Learn. Mem."},{"key":"B116","doi-asserted-by":"publisher","first-page":"e28441","DOI":"10.1371\/journal.pone.0028441","article-title":"Regulation of brain-derived neurotrophic factor exon IV transcription through calcium responsive elements in cortical neurons","volume":"6","author":"Zheng","year":"2011","journal-title":"PLoS One"},{"key":"B117","first-page":"188","article-title":"Regulation of brain-derived neurotrophic factor expression in neurons","volume":"4","author":"Zheng","year":"2012","journal-title":"Int. J. Physiol. Pathophysiol. Pharmacol."},{"key":"B118","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1002\/jnr.22321","article-title":"Intracellular calcium and calmodulin link brain-derived neurotrophic factor to p70S6 kinase phosphorylation and dendritic protein synthesis","volume":"88","author":"Zhou","year":"2010","journal-title":"J. Neurosci. Res."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.949384\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T07:59:59Z","timestamp":1663315199000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.949384\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,16]]},"references-count":118,"alternative-id":["10.3389\/fphar.2022.949384"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.949384","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,16]]},"article-number":"949384"}}