Separation of LEC layer III neuronal excitability in normal aging

Aging is often associated with a decline in hippocampus-dependent learning and memory, although not all subjects exhibit learning impairments as they age. Previous research has shown that within the CA1 region of the hippocampus, there is a separation in the aging population in terms of intrinsic excitability. CA1 neurons from aged subjects that are learning impaired have decreased excitability relative to neurons from young animals, while neurons from aged subjects that retain learning ability have comparable excitability to young counterparts. The current project focuses on determining whether intrinsic excitability within the principal neurons of the entorhinal cortex also underlies learning deficits in aged subjects. The entorhinal cortex relays information from cortical regions to the hippocampus and is highly susceptible to aging-related changes. Specifically, the lateral portion of the entorhinal cortex (LEC) been suggested to support hippocampus-dependent temporal associative learning and is also the initial site of manifestation for Alzheimer’s disease. Therefore, whole cell current clamp recordings were performed on the pyramidal neurons of layer III of the LEC from young adult (3-6 month old) and aged (29-32 month old) F1 F344xBN hybrid rats. These neurons project directly to CA1 of the hippocampus. Measures of intrinsic excitability include accommodation and postburst afterhyperpolarization (AHP). Our preliminary results indicate a separation in the aging population in excitability in the LEC, such that there is a population of neurons that are less excitable and another population of neurons that remain as excitable as young counterparts. The results are similar to previous data from the CA1 region of the hippocampus and suggest LEC intrinsic excitability may also be a measure and mechanism supporting learning. Identification of these changes in aging will point to a potential target for future therapeutics in alleviating aging-related learning and memory deficits.