The formation of neurofibrillary tangles from the assembly of 
hyperphosphorylated tau leads to dendritic and axonal instability, synaptic 
degeneration, and neuronal loss. To understand the early physiological 
consequences of aberrant tau expression, we characterized the physiology of CA1 
pyramidal neurons in rTg4510 female mice and non-transgenic (wt) littermate 
controls. We studied mice at the age of 10-12 weeks where only minimal 
hyperphosphorylated pretangle tau was present, and 22-24 weeks old mice with 
significant neurofibrillary tangle pathology. Our electrophysiological analysis 
included input-output relation, paired-pulse facilitation, and whole cell 
patch-clamp recordings of neurons to measure action potential threshold and 
action potential properties, chord-conductance, and characterization of AMPA 
receptor mediated synaptic transmission. We found that the input-output relation 
in field (excitatory postsynaptic potentials, EPSP) and whole cell recordings 
(excitatory postsynaptic currents, EPSC) were impaired in rTg4510 mice compared 
to wt controls at both ages. We measured a diminished tail current charge after 
depolarizing voltage input in rTg4510 mice compared to wt in both young and aged 
mice. Additionally, mini-EPSC properties (peak and decay time) were essentially 
similar between genotypes and age groups investigated. Surprisingly, in the 
22-24 week old group, the mini-EPSC frequency was significantly increased 
(interevent interval 0.8 ± 0.1 in wt compared to 0.3 ± 0.1 in rTg4510 mice). 
These data indicate that the developmentally regulated expression of human P301L 
tau in CA1 pyramidal neurons coincide with changes in neuronal excitability but 
also that significant presynaptic changes occur late during the progression of 
tau pathology in this mouse model.