title: Opposing Effects of Maternal Hypo- and Hyperthyroidism on the Stability of Thalamocortical Synapses in the Visual Cortex of Adult Offspring.
abstract: Insufficient or excessive thyroid hormone (TH) levels during fetal development can cause long-term neurological and cognitive problems. Studies in animal models of perinatal hypo- and hyperthyroidism suggest that these problems may be a consequence of the formation of maladaptive circuitry in the cerebral cortex, which can persist into adulthood. Here we used mouse models of maternal hypo- and hyperthyroidism to investigate the long-term effects of altering thyroxine (T4) levels during pregnancy (corresponding to embryonic days 6.5-18.5) on thalamocortical (TC) axon dynamics in adult offspring. Because perinatal hypothyroidism has been linked to visual processing deficits in humans, we performed chronic two-photon imaging of TC axons and boutons in primary visual cortex (V1). We found that a decrease or increase in maternal serum T4 levels was associated with atypical steady-state dynamics of TC axons and boutons in V1 of adult offspring. Hypothyroid offspring exhibited axonal branch and bouton dynamics indicative of an abnormal increase in TC connectivity, whereas changes in hyperthyroid offspring were indicative of an abnormal decrease in TC connectivity. Collectively, our data suggest that alterations to prenatal T4 levels can cause long-term synaptic instability in TC circuits, which could impair early stages of visual processing.
authors.affiliation: Department of Pediatrics, Child Health Research Institute, University of Florida College of Medicine, Gainesville, FL 32610, USA.|Department of Nuclear Medicine, University Medical Center, University RWTH Aachen, 52074 Aachen, Germany.
authors.forename: Marie-Therese J
authors.initials: MJ
authors.lastname: Strobl
authors.affiliation: Department of Pediatrics, Child Health Research Institute,University of Florida College of Medicine, Gainesville, FL 32610, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Freeman
authors.affiliation: Department of Pediatrics, Child Health Research Institute,University of Florida College of Medicine, Gainesville, FL 32610, USA.
authors.forename: Jenica
authors.initials: J
authors.lastname: Patel
authors.affiliation: Department of Pediatrics, Child Health Research Institute,University of Florida College of Medicine, Gainesville, FL 32610, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Poulsen
authors.affiliation: Department of Pediatrics, Child Health Research Institute,University of Florida College of Medicine, Gainesville, FL 32610, USA.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Wendler
authors.affiliation: Department of Pediatrics, Child Health Research Institute,University of Florida College of Medicine, Gainesville, FL 32610, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rivkees
authors.affiliation: Department of Pediatrics, Child Health Research Institute,University of Florida College of Medicine, Gainesville, FL 32610, USA.
authors.forename: Jason E
authors.initials: JE
authors.lastname: Coleman
mesh_terms: D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D013956:Antithyroid Agents / Q000633:toxicity; D001931:Brain Mapping; D004195:Disease Models, Animal; D005260:Female; D005865:Gestational Age; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006980:Hyperthyroidism / Q000000981:diagnostic imaging / Q000473:pathology*; D007037:Hypothyroidism / Q000000981:diagnostic imaging / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D008297:Male; D008713:Methimazole / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D059906:Neuroimaging; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000503:physiopathology*; D013569:Synapses / Q000502:physiology*; D016704:Synapsins / Q000235:genetics / Q000378:metabolism; D013788:Thalamus / Q000000981:diagnostic imaging / Q000473:pathology*; D013974:Thyroxine / Q000633:toxicity; D013997:Time Factors; D014161:Transduction, Genetic; D014793:Visual Cortex / Q000000981:diagnostic imaging / Q000473:pathology*
chemical_list: D013956:Antithyroid Agents; D016704:Synapsins; D049452:Green Fluorescent Proteins; D008713:Methimazole; D013974:Thyroxine
keywords: development; synapse; thalamocortical; thyroid hormones; two-photon