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Cortical and subcortical innervation of band heterotopia after developmental thyroid hormone insufficiency
Citation:
Ramosi, R. L., C. Wang, D. P. McCloskey, M. E. GILBERT, AND J. H. Goodman. Cortical and subcortical innervation of band heterotopia after developmental thyroid hormone insufficiency. Presented at Society for Neuroscience Annual Meeting, San Diego, CA, November 13 - 17, 2010.
Impact/Purpose:
These data point to an important role of thyroid hormone in neuronal migration and cortical function.
Description:
The characteristic laminated cytoarchitecture of the neocortex emerges from the orderly proliferation and migration of neurons during corticogenesis. Not surprisingly, developmental disorders affecting the laminar positioning of cortical neurons can have dramatic affects on cognitive function and are often associated with epilepsy. Previously we demonstrated that modest thyroid hormone insufficiency during prenatal periods has lasting effects on cognitive function (Gilbert & Sui 2006), synaptic function and plasticity (Gilbert & Sui 2006; Gilbert et al. 2007), and results in cortical malformation (Goodman & Gilbert, 2007) in rats. In particular, reduction ofthyroid hormone levels with propylthiouracil (PTU) caused bilateral subcortical band heterotopia in midline cortical regions that were made up diverse subtypes of neurons as well as glia. These data point to an important role of thyroid hormone in neuronal migration and cortical function. In the present report we describe immunohistochemical and anterograde tract-tracing studies that reveal cortical and subcortical connections into subcortical band heterotopia (SBH) after reduction of thyroid hormone by PTU (lOppm delivered to dam through drinking water) from embryonic day 6 until birth of pups. First, in brain sections from adults containing SBH, histochemistry for myelin revealed numerous myelinated fibers present in heterotopia. These data were confirmed with immunocytochemistry against myelin basic protein (n=5) as well as immunostaining of neurofilament (200kDa). Unilateral injections of the anterograde tracer Biotinylated Dextran Amine (BDA, 10K mw) into the caudal cortical regions of adult rats revealed labeled axons in ipsilateral and contralateral SBH (n=9). In contrast, injections made in frontal cortical regions resulted in no labeled axons in SBH (n=5). In order to assess possible subcortical input into SBH, we used immunocytochemistry for tyrosine hydroxylase (TH). We observed TH immunoreactive fibers in SBH (n=5) indicating possible afferents from brainstem or midbrain structures.Together these findings indicate that SBH receive cortical and possibly subcortical afferents and compliment our previous findings using retrograde tracers which revealed efferents connections of neurons in SBH to distinct cortical regions (Goodman et al. SFN 2008). How afferent and efferent connections of SBH affect brain function is a topic of ongoing investigation. (Does not reflect US EPA policy).