Longitudinal studies reveal age-dependent relatively rapid-onset and persistent LTP impairment in individual TG rats. (a,b) The age of onset and time course of the development of the deficit in LTP was assessed using a longitudinal study design. (a) We evaluated the ability of the 200 Hz HFS protocol to induce potentiation at weekly intervals in individual animals between 3 and 4 months of age. The top pair of panels shows time-course graphs of LTP induced by repeated weekly application of the HFS protocol in two WT control animals. The HFS triggered similar magnitude LTP each time during the repeated recording sessions. In contrast, the ability to induce STP and LTP was impaired at slightly different ages in individual TG rats as shown in the bottom pair of panels. Arrow heads: HFS application Horizontal lines: 100% baseline EPSP amplitude Calibration bars: Vertical, 50% change in EPSP amplitude; Horizontal, 30 min. (b) Summary grouped data for the magnitude of STP and LTP tracked repeatedly in the same WT and TG rats at fortnightly intervals between 3 and 6 months of age. The ability of the HFS protocol to induce LTP was lost between 3 and 4 months of age and the loss persisted for the remaining 2-month recording period. Values in (b) are the mean + S.E.M. EPSP amplitude at 3 h after the HFS. *P < 0.05 compared with WT.