Neuronal hypofunction and network dysfunction in a mouse model at early stage of tauopathy

In the JNPL3 tauopathy mouse model, a reduction in neuronal Ca²⁺ activity was observed in the motor cortex of awake and behaving animals during the early stage of tauopathy. This neuronal deficit was more pronounced under running conditions. The presence of tau pathology affected the local neuronal circuitry, as evidenced by an increased basal Ca²⁺ activity synchrony and altered profiles of running-related neuronal responses in the motor cortex. Underlying mechanisms may be linked to impairments in excitatory synaptic transmission and altered excitatory/inhibitory balance in this region, resulting from the accumulation of pathological tau.