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Regional differences in dendritic morphology of medium spiny striatal neurons in Foxp2 mice are influenced by substitution at position T302N

The transcription factor FOXP2 (Forkhead-box-protein-P2) is involved in speech and language development and carries two amino acid substitutions (T303N, N325S), which were probably positively selected during human evolution. When these two substitutions are introduced into the endogenous Foxp2 gene of mice (Enard et al, Cell 137:861, 2009), the animals show longer dendrites in Foxp2-positive cells that are part of basal ganglia circuits such as medium spiny neurons (MSN) in the striatum (Reimers-Kipping et al, Neuroscience 175:75, 2011). Using a motorized Olympus-BX61 microscope-computer system and Neurolucida software, we analysed regional differences in dendritic morphology and spine density of Golgi-Cox impregnated MSNs in the rostral, dorso-medial (DMS), dorso-lateral (DLS) and caudal striatum in mice homozygous for the two human substitutions as well as in mice carrying only the substitution at position 302 in their endogenous Foxp2 gene. Both mouse lines presented the same patterns of differences in dendritic morphology and spine density relative to wild-type mice. Specifically, the caudal region shows a slight outgrowth of new segments, DMS and DLS show a slight increase in segment length, spine density and a slight decrease in dendrite diameter whereas the rostral striatum shows a decrease in segment length and an increase in dendrite thickness. Our findings suggest that the human-specific substitution at position T302N causes a region-specific reorganization of circuitry in the striatum.

Foxp2; striatum; medium spiny neurons

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