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

Abnormal deposition of the microtubule-associated protein tau has long been associated with spine loss and neuronal death in neurodegenerative diseases. Elucidating how pathological tau affects synaptic activity in vivo and whether individual synaptic properties dictate the survival fate of dendritic spines is central to understanding disease progression. Here we examined the visual response properties of layer 2/3 primary visual cortical dendrites and spines, using longitudinal two-photon calcium imaging in the P301S mouse model of tauopathy. Neuronal outputs in tau mutant mice were hyperactive and poorly tuned whereas dendritic spine responses were also poorly tuned but hypoactive. Moreover, in controls, stable spines were larger in size and more sharply tuned but less active compared to those that turned over. Such a function-to-structure relationship was absent in mutants. Our findings illustrate how tauopathy disrupts the preferential maintenance of well-tuned inputs in healthy neural circuitry, resulting in poorly tuned visual responses.