Description:

"Mechanisms of Learning in Aging and Alzheimer’s Disease"

Progress and next steps on four areas of research will be reviewed. Lateral Entorhinal Cortex provides reciprocal connections between the temporal lobe and the hippocampus, is a site of early changes in AD, and have neurons that exhibit persistent firing. LEC Layer III pyramidal neurons have been studied in associative learning, in aging, and in a rat model of AD. The functional changes observed indicate that LEC is playing a pivotal role in each. Alzheimer’s Disease has been preclinically modeled primarily in mice. We have begun characterization of the Tg-F344 AD rat model as the rat is more readily trained and has a larger brain than mice. Progress in characterizing this rat model behaviorally, with immunohistochemistry and with mass spectrometry will be described. The Paired Associate Learning (PAL) touch screen learning task has been implemented in Long Evans rats. We will use this behavioral task to determine the effectiveness and phase dependence (relative to on-going theta activity) of electrical stimulation of hippocampal afferents in order to understand mechanisms underlying facilitative effects of transcranial magnetic stimulation applied to human subjects. Miniscope recordings of single neuron calcium activity has been developed for rat CA1 neurons. Initial experiments have identified spatial fields in recordings of hundreds of neurons. Future experiments will identify how populations of neurons change as hippocampus-dependent trace eyeblink conditioning is acquired; and in response to our rat TMS model stimulation