engleski

Regional differences in dendritic morphology and spine density of striatal medium spiny neurons in Foxp2 mice

Introduction: The extent of language capability sets humans apart from their closest living relatives, the chimpanzees. The transcription factor FOXP2, which is required for speech and language development, carries two amino acid substitutions (T303N, N325S) on the hominine lineage which were likely positively selected during human evolution. When the human variant of the FOXP2 protein is expressed in mice these animals show an increased dendritic complexity of neurons that are a part of the basal ganglia circuitry and highly express FOXP2, e.g. striatal medium spiny neurons(MSN). Materials and methods: The current investigation involves analysing dendritic morphology and spine density in Golgi-Cox impregnated MSN in adult mice homozygous for the FOXP2 human variant (Foxp2hum/hum -T302N, N324S) and in two additional mouse strains where one carries substitution at position 302 (T302N) while the other carries it at position 324 (N324S) in their endogenous Foxp2 gene. Analysis will include regional comparison of dendritic morphology and spine density of MSN striatum (dorso-medial, dorso- lateral, rostral and caudal region) in all mice lines, as well as a comparison with the wild-type(Foxp2 wt/wt)line. Results: The previous study has shown that in Foxp2hum/hum mice MSN tend to have around 20% longer dendritic trees, but present results of dendritic morphology of MSN in dorso-medial striatum in Foxp2hum/hum mice did not show any significant differences. Interestingly, in T302N line there was a tendency for terminal segments to be longer and thinner when compared to Foxp2wt/wt, both in dorso-medial and dorso-lateral striatum. Discussion: Present results did not confirm previous observation of increased dendritic morphology of MSN in Foxp2hum/hum mice line. In addition, the results do not fit with electrophysiological data, as well as with decrease in dopamine levels in some striatal regions. It is possible that the effect is related only to a part of MSN population or it has a clear regional effect (MSN in rostral and caudal striatum will be reconstructed). It is also possible that changes are related to spine density (analysis in process) and not with the dendritic size. Present results support the hypothesis that human specific changes at position T302N are responsible for neuronal changes related with “language” circuitry and a view that expansion of cerebral cortex is needed to allow significant functional changes related with appearance of language.

Foxp2; speech development; cortico-striatal circuitry; dopamine

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