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Age-dependent alterations of long-term synaptic plasticity in thyroid-deficient rats.
Hippocampus 2003; 13(7):816-25H

Abstract

Thyroid hormone deficiency during a critical period of development profoundly affects cognitive functions such as attention, learning, and memory, but the synaptic alterations underlying these deficits remain unexplored. The present study examines the effect of congenital hypothyroidism on long-term synaptic plasticity. This plasticity is believed to be essential for learning and memory and for activity-dependent regulation of synapse formation in the developing brain. We found that the neonatal expression of long-term potentiation (LTP), long-term depression (LTD), depotentiation, and de-depression in hippocampal slices from hypothyroid animals was similar to that of controls. To examine the postnatal development of these plasticities, we used slices from neonatal (2-3 weeks) and adult (7-8 weeks) rats. This work demonstrates that the ability to express all these forms of synaptic plasticity is reduced in an age-dependent manner in control rats. LTP and depotentiation are also downregulated in adult hypothyroid rats, but we have found that de-depression is not affected during maturation. In addition, these animals express LTD at ages at which controls fail to induce it. In contrast, input/output experiments have shown greater levels of basal synaptic efficacy in hypothyroid adults, and this effect is probably related to the higher probability of release observed by paired-pulse experiments. Nevertheless, these effects appear to be unrelated to the differences observed in long-term synaptic plasticity, as no correlation was found between basal synaptic efficacy and the degree of LTD and de-depression. Furthermore, the NMDA-receptor antagonist amino-phosphonopentanoic acid (APV) completely blocked LTD, which suggests a postsynaptic locus of this alteration. Because LTD has been associated with novelty acquisition, we suggest that the greater LTD observed in adult hypothyroid rats might be related to the hyperactivity of these animals. However, other possibilities such as a retarded maturation of synaptic plasticity must be taken into account.

Authors+Show Affiliations

Departament de Fisiología, Facultad de Medicina, Universidad Complutense, Ciudad Universitaria, Madrid, Spain.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14620877

Citation

Vara, H, et al. "Age-dependent Alterations of Long-term Synaptic Plasticity in Thyroid-deficient Rats." Hippocampus, vol. 13, no. 7, 2003, pp. 816-25.
Vara H, Muñoz-Cuevas J, Colino A. Age-dependent alterations of long-term synaptic plasticity in thyroid-deficient rats. Hippocampus. 2003;13(7):816-25.
Vara, H., Muñoz-Cuevas, J., & Colino, A. (2003). Age-dependent alterations of long-term synaptic plasticity in thyroid-deficient rats. Hippocampus, 13(7), pp. 816-25.
Vara H, Muñoz-Cuevas J, Colino A. Age-dependent Alterations of Long-term Synaptic Plasticity in Thyroid-deficient Rats. Hippocampus. 2003;13(7):816-25. PubMed PMID: 14620877.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Age-dependent alterations of long-term synaptic plasticity in thyroid-deficient rats. AU - Vara,H, AU - Muñoz-Cuevas,J, AU - Colino,A, PY - 2003/11/19/pubmed PY - 2004/1/22/medline PY - 2003/11/19/entrez SP - 816 EP - 25 JF - Hippocampus JO - Hippocampus VL - 13 IS - 7 N2 - Thyroid hormone deficiency during a critical period of development profoundly affects cognitive functions such as attention, learning, and memory, but the synaptic alterations underlying these deficits remain unexplored. The present study examines the effect of congenital hypothyroidism on long-term synaptic plasticity. This plasticity is believed to be essential for learning and memory and for activity-dependent regulation of synapse formation in the developing brain. We found that the neonatal expression of long-term potentiation (LTP), long-term depression (LTD), depotentiation, and de-depression in hippocampal slices from hypothyroid animals was similar to that of controls. To examine the postnatal development of these plasticities, we used slices from neonatal (2-3 weeks) and adult (7-8 weeks) rats. This work demonstrates that the ability to express all these forms of synaptic plasticity is reduced in an age-dependent manner in control rats. LTP and depotentiation are also downregulated in adult hypothyroid rats, but we have found that de-depression is not affected during maturation. In addition, these animals express LTD at ages at which controls fail to induce it. In contrast, input/output experiments have shown greater levels of basal synaptic efficacy in hypothyroid adults, and this effect is probably related to the higher probability of release observed by paired-pulse experiments. Nevertheless, these effects appear to be unrelated to the differences observed in long-term synaptic plasticity, as no correlation was found between basal synaptic efficacy and the degree of LTD and de-depression. Furthermore, the NMDA-receptor antagonist amino-phosphonopentanoic acid (APV) completely blocked LTD, which suggests a postsynaptic locus of this alteration. Because LTD has been associated with novelty acquisition, we suggest that the greater LTD observed in adult hypothyroid rats might be related to the hyperactivity of these animals. However, other possibilities such as a retarded maturation of synaptic plasticity must be taken into account. SN - 1050-9631 UR - https://www.unboundmedicine.com/medline/citation/14620877/Age_dependent_alterations_of_long_term_synaptic_plasticity_in_thyroid_deficient_rats_ L2 - https://doi.org/10.1002/hipo.10132 DB - PRIME DP - Unbound Medicine ER -