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Previous studies showed that perinatal deficiency of TH or impairment of its signaling severely affect brain development, especially the development of the \u03b3\u2010aminobutyric acid (GABA) system, but cellular and molecular targets of the hormone are only partly uncovered. In the present study, we focused on the developing rat hippocampus which was confirmed to be one of the regions highly sensitive to TH status, and found two new targets of the hormone among the pre\u2010 and post\u2010synaptic components of the GABAergic system. One was glutamic acid decarboxylase 65 (GAD65), the protein level of which was reduced to less than 50% of control in the hippocampus of hypothyroid rats (obtained by administering 0.025% methimazole in drinking water to pregnant dams from gestational day 15 until 4 weeks postpartum) and recovered to control levels by daily thyroxine\u2010replacement after birth. Reduction in GAD65 protein was correlated immunohistochemically with a 37% reduction in the number of GAD65\u2010positive cells as well as a reduction in GAD65\u2010positive processes. In contrast, the other GAD isotype, GAD67, was not affected by TH status. A subpopulation of GABAergic neurons containing parvalbumin was also confirmed to be highly dependent on TH status. The second target of thyroid hormone was neuron\u2010specific K<jats:sup>+<\/jats:sup>\/Cl<jats:sup>\u2212<\/jats:sup>co\u2010transporter, KCC2, which is responsible for switching of GABA action from excitatory to inhibitory. In the euthyroid hippocampus, a sharp rise of<jats:italic>kcc2<\/jats:italic>expression was observed at postnatal day (PND)10 which was followed by a large increase in KCC2 protein at PND15. This transient rise in<jats:italic>kcc2<\/jats:italic>expression was completely suppressed by hypothyroidism, resulting in nearly 80% reduction in KCC2 protein at PND15. These results indicate that the development of GABAergic terminals and the excitatory to inhibitory maturation of GABA signaling are strongly dependent on TH.<\/jats:p>","DOI":"10.1016\/j.ijdevneu.2013.09.007","type":"journal-article","created":{"date-parts":[[2013,9,26]],"date-time":"2013-09-26T01:07:19Z","timestamp":1380157639000},"page":"751-761","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Thyroid hormone\u2010dependent development of the GABAergic pre\u2010 and post\u2010synaptic components in the rat hippocampus"],"prefix":"10.1002","volume":"31","author":[{"given":"Erika","family":"Sawano","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biological Science School of Science and Engineering Aoyama Gakuin University 5\u201010\u20101 Fuchinobe, Chou\u2010ku Sagamihara Kanagawa 252\u20105258 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biological Science School of Science and Engineering Aoyama Gakuin University 5\u201010\u20101 Fuchinobe, Chou\u2010ku Sagamihara Kanagawa 252\u20105258 Japan"},{"name":"National Institute of Neuroscience National Center of Neurology and Psychiatry (NCNP) 4\u20101\u20101 Ogawa\u2010higashi Kodaira Tokyo 187\u20108502 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Negishi","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biological Science School of Science and Engineering Aoyama Gakuin University 5\u201010\u20101 Fuchinobe, Chou\u2010ku Sagamihara Kanagawa 252\u20105258 Japan"},{"name":"Department of Physiology Faculty of Pharmacy Meijo University 150 Yagotoyama, Tempaku\u2010ku Nagoya Aichi 468\u20108503 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Tashiro","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biological Science School of Science and Engineering Aoyama Gakuin University 5\u201010\u20101 Fuchinobe, Chou\u2010ku Sagamihara Kanagawa 252\u20105258 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,9,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00351"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0892-0362(91)90077-A"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn920"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00017.2006"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1330390"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.03.003"},{"issue":"6","key":"e_1_2_6_8_1","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1523\/JNEUROSCI.12-06-02288.1992","article-title":"Spatial and temporal expression of alpha\u2010 and beta\u2010thyroid hormone receptor mRNAs, including the beta 2\u2010subtype, in the developing mammalian nervous system","volume":"12","author":"Bradley D.J.","year":"1992","journal-title":"J. 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