biostudies-literatureJi CNIA NIH HHSAlzheimer's Association Research FellowshipsNINDS NIH HHSNational Institutes of HealthNIH HHS7954-7970https://www.ebi.ac.uk/biostudies/studies/S-EPMC11567809biostudies-literatureUnknown20(11)<h4>Introduction</h4>It is unclear how early neuronal deficits occur in tauopathies, if these are associated with changes in neuronal network activity, and if they can be alleviated with therapies.<h4>Methods</h4>To address this, we performed in vivo two-photon Ca²⁺ imaging in tauopathy mice at 6 versus 12 months, compared to controls, and treated the younger animals with a tau antibody.<h4>Results</h4>Neuronal function was impaired at 6 months but did not deteriorate further at 12 months, presumably because cortical tau burden was comparable at these ages. At 6 months, neurons were mostly hypoactive, with enhanced neuronal synchrony, and had dysregulated responses to stimulus. Ex vivo, electrophysiology revealed altered synaptic transmission and enhanced excitability of motor cAlzheimer's & dementia : the journal of the Alzheimer's AssociationNeuronal hypofunction and network dysfunction in a mouse model at an early stage of tauopathy.PMC11567809R01 AG032611AARF-22-924783 (Y.J.)R01 NS077239R21 AG069475AARF-22-926735 (C.J.)RF1 NS120488R01 NS120488R01 NS120488 (E.M.S.)R21 AG059391AARFD-22-926379 (A.M-A)Yang XJiang YJi CEleish MMartin-Avila AWu QTetlow AMSong SCSigurdsson EMLin YZhou YGan WfalseNeuronal hypofunction and network dysfunction in a mouse model at an early stage of tauopathy.<h4>Introduction</h4>It is unclear how early neuronal deficits occur in tauopathies, if these are associated with changes in neuronal network activity, and if they can be alleviated with therapies.<h4>Methods</h4>To address this, we performed in vivo two-photon Ca²⁺ imaging in tauopathy mice at 6 versus 12 months, compared to controls, and treated the younger animals with a tau antibody.<h4>Results</h4>Neuronal function was impaired at 6 months but did not deteriorate further at 12 months, presumably because cortical tau burden was comparable at these ages. At 6 months, neurons were mostly hypoactive, with enhanced neuronal synchrony, and had dysregulated responses to stimulus. Ex vivo, electrophysiology revealed altered synaptic transmission and enhanced excitability of motor c2024-01-01T00:00:00Z2024 Nov2026-07-16T22:36:40.533Z2025-04-07T04:31:05.704ZS-EPMC115678093936811310.1002/alz.14273