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Activity of both excitatory and inhibitory neurons is modulated by inhibitory signalling of the GABAergic and glycinergic systems. Mechanisms that regulate formation, maturation, refinement, and maintenance of inhibitory synapses are established in early life. Deviations from ideal excitatory and inhibitory balance, such as down-regulated inhibition, are linked with many neurological diseases, including epilepsy, schizophrenia, anxiety, and autism spectrum disorders. In the mammalian forebrain, GABA is the primary inhibitory neurotransmitter, binding to GABA receptors, opening chloride channels and hyperpolarizing the cell. We review the involvement of down-regulated inhibitory signalling in neurological disorders, possible mechanisms for disease progression, and targets for therapeutic intervention. We conclude that transgenic models of disrupted inhibitory signalling\u2014in GAD67+\/\u2212 and VGAT\u2212\/\u2212 mice\u2014are useful for investigating the effects of down-regulated inhibitory signalling in a range of neurological diseases.<\/jats:p>","DOI":"10.3390\/ijms23147965","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T08:28:25Z","timestamp":1658219305000},"page":"7965","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Investigating the Role of GABA in Neural Development and Disease Using Mice Lacking GAD67 or VGAT Genes"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7548-0905","authenticated-orcid":false,"given":"Erika","family":"Bolneo","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pak Yan S.","family":"Chau","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9821-8478","authenticated-orcid":false,"given":"Peter G.","family":"Noakes","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane 4072, Australia"},{"name":"Queensland Brain Institute, The University of Queensland, Brisbane 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9189-4430","authenticated-orcid":false,"given":"Mark C.","family":"Bellingham","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6496","DOI":"10.1073\/pnas.94.12.6496","article-title":"Cleft palate and decreased brain \u03b3-aminobutyric acid in mice lacking the 67-kDa isoform of glutamic ac-id\u2009decarboxylase","volume":"94","author":"Asada","year":"1997","journal-title":"Proc. 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