Truncated thyroid hormone receptors .DELTA.TR.alpha.1 and .DELTA.TR.alpha.2 have been discovered to play a role in actin-based endocytosis, e.g., in the nervous system. The invention relates to methods of discovering ligands effective in modulating endocytosis and transgenic mice with altered expression of .DELTA.TR.alpha.1 and .DELTA.TR.alpha.2. The invention is useful for the discovery and testing of compounds for treating disorders of the nervous system such as depression.