Analysis of Thyroid Response Element Activity during Retinal Development

Thyroid hormone (TH) signaling components are expressed during retinal development in dynamic spatial and temporal patterns. To probe the competence of retinal cells to mount a transcriptional response to TH, reporters that included thyroid response elements (TREs) were introduced into developing retinal tissue. The TREs were placed upstream of a minimal TATA-box and two reporter genes, green fluorescent protein (GFP) and human placental alkaline phosphatase (PLAP). Six of the seven tested TREs were first tested in vitro where they were shown to drive TH-dependent expression. However, when introduced into the developing retina, the TREs reported in different cell types in both a TH-dependent and TH-independent manner, as well as revealed specific spatial patterns in their expression. The role of the known thyroid receptors (TR), TRα and TRβ, was probed using shRNAs, which were co-electroporated into the retina with the TREs. Some TREs were positively activated by TR+TH in the developing outer nuclear layer (ONL), where photoreceptors reside, as well as in the outer neuroblastic layer (ONBL) where cycling progenitor cells are located. Other TREs were actively repressed by TR+TH in cells of the ONBL. These data demonstrate that non-TRs can activate some TREs in a spatially regulated manner, whereas other TREs respond only to the known TRs, which also read out activity in a spatially regulated manner. The transcriptional response to even simple TREs provides a starting point for understanding the regulation of genes by TH, and highlights the complexity of transcriptional regulation within developing tissue

Dorsal Hippocampal Administration of Triiodothyronine Enhances Long-Term Memory for Trace Cued and Delay Contextual Fear Conditioning in Rats

Thyroid hormones play critical roles in brain maturation and cognitive functions. The present study investigated the role of thyroid hormone in emotional learning and memory using trace and delay contextual and cued fear conditioning tasks, respectively. Rats were administered triiodothyronine (T3) into the dorsal hippocampal area 10 min before training or immediately after training, and were scored for freezing behaviour in the same context and in a novel context with and without an auditory cue that had been paired previously with an aversive stimulus, a foot shock. Rats administered T3 before and after training both exhibited significantly increased long-term fear memory in the trace cued and the delay contextual fear conditioning procedures compared to their control groups. The T3-administered rats were not significantly different from their respective controls on the acquisition and short-term fear memory in the trace and delay fear conditioning tasks. No significant difference on long-term trace contextual and delay cued fear memory, respectively, was found. These results indicate that the observed T3-induced enhancement of long-term contextual and cued fear memory was specific to the hippocampus-dependent conditioning tasks. These findings are the first to demonstrate that infusion of T3 into the dorsal hippocampus can improve performance on an emotional memory task. © 2006 The Authors. Journal Compilation 2006 Blackwell Publishing Ltd