Functional and structural characterization of dendritic spine pathology in a mouse model of tauopathy

SUMMARY Abnormal deposition of the microtubule-associated protein tau has long been associated with neurodegenerative diseases. While spine loss and neuronal death are hallmarks of tauopathy, how pathological tau affects synaptic activity in vivo and whether functional properties of individual synapses dictate the survival fate of dendritic spines remain elusive. Here we examined the visual response properties of dendrites and spines of layer 2/3 primary visual cortical neurons, using longitudinal two-photon calcium imaging in P301S mouse model of tauopathy. We found that neuronal outputs in tau mutant mice were hyperactive and poorly tuned whereas dendritic spine responses were also poorly tuned but hypoactive. Moreover, we found that spines that were stably retained across two imaging sessions were larger in size and more sharply tuned but less active compared to those that turned over in controls. Such structure-to-function relationship was not observed in mutants. Our findings illustrate how the preferential maintenance of well-tuned inputs in healthy neural circuitry may be affected by tauopathy, resulting in neurons with poorly tuned visual responses.