Modeling brain reserve: experience-dependent neuronal plasticity in healthy and Huntington's disease transgenic mice.
Nithianantharajah J., Barkus C., Vijiaratnam N., Clement O., Hannan AJ.
OBJECTIVE: Experience-dependent modification of neuronal and synaptic connectivity may represent a mechanism of relevance to the theory of brain or cognitive reserve. The authors have investigated structural correlates of synaptic function and plasticity, through analysis of dendritic morphology after environmental enrichment, a paradigm for investigation of experience-dependent plasticity. DESIGN: Using a transgenic mouse model for Huntington's disease (HD), R6/1 and wild-type mice were exposed to either standard housing or environmental enrichment from 4 until 20 weeks of age. MEASUREMENTS: Golgi-stained neurons were analyzed for dendritic branching and spine density in the hippocampus, somatosensory, and motor cortices. RESULTS: Symptomatic R6/1 HD mice showed an absence of dendritic spine pathology, although there were region-specific decreases in dendritic diameter, branching, and complexity, as well as neuronal soma area. Furthermore, the authors demonstrate that environmental enrichment induces subtle, region-specific effects on dendritic morphology and spine density in wild-type control animals, but had less of an effect in HD mice, which has implications for our understanding of the cellular mechanisms mediating experience-dependent plasticity in HD. CONCLUSIONS: These results show that gross structural alterations are less likely to contribute to the cognitive, psychiatric, and motor symptoms in HD, and suggest that subtle molecular and functional changes may underlie HD symptomatology. Furthermore, the enrichment-induced effects on dendritic morphology may contribute to strengthening neuronal and synaptic connectivity, and provide a mechanism for how the brain may more efficiently use existing neuronal networks and recruit alternate networks when required. These findings not only have implications for HD, but the authors also propose that the concept of enrichment and cognitive reserve may be relevant to many brain disorders, including neurologic and psychiatric, where cognitive dysfunction is a part of symptomatology.