The purpose of the current thesis was twofold: (1) to examine various factors that might be contributing to age-related learning and memory deficits specifically related to the hippocampus, and (2) to validate our rat model of aging, employing a multilevel analysis. We found age-related deficits on both spatial and non-spatial hippocampus-dependent tasks that were accompanied by structural alterations observed both in vivo (volume, but not neuronal metabolic function) and post mortem (neuronal density and neurogenesis, but not synaptic or mitochondrial density). Furthermore, our results suggest that the observed hippocampal structural changes, namely decreased volume and neurogenesis, predict learning and memory deficits, and both can be accounted for by neurogenic reduction. In addition, the above-mentioned pattern of age-related deficits closely resembles that seen in humans, suggesting the present rat version of aging to be a very useful model for investigating hippocampal aging in humans.

It is generally believed that the hippocampus is not required for simple discrimination learning. However, a small number of studies have shown that hippocampus damage impairs retention of a previously learned visual discrimination task. We propose that, although simple discrimination learning may proceed in the absence of the hippocampus, it plays an important role in this type of learning when it is intact. In order to test the role of the hippocampus in simple discrimination learning, we performed a series of experiments utilizing a two-choice picture discrimination task. Our experiments confirm that rats readily learn simple two-choice picture discriminations after hippocampus damage. However, if such discriminations are first learned while the hippocampus is intact, subsequent hippocampus damage causes severe retrograde amnesia for the discriminations. Furthermore, retrograde amnesia for simple picture discriminations was equally severe when the interval between training and damage was 1 d or 60 d; remote picture memories are not spared. Similarly, the rule or schema underlying a recently or remotely acquired picture discrimination learning set was lost after hippocampus damage. The severity of retrograde amnesia for simple picture discriminations is negatively correlated with the volume of spared hippocampus tissue. Thus, the hippocampus plays an essential role in long-term memories supporting simple picture discriminations.Much of what is known about the role of the hippocampus in learning and memory comes from studies of anterograde amnesia after hippocampus damage. There is a consensus that the ability to learn simple discrimination tasks typically is not affected by anterograde amnesia (Broadbent et al. 2007). In simple discrimination tasks, usually involving many trials of training, one stimulus is reinforced and another is not. As such, simple discriminations are among the class of problems that have linear solutions (i.e., during training, S+ acquires greater excitatory associative strength than S‫.)מ‬ Numerous experiments have confirmed that anterograde amnesia after hippocampus damage does not affect simple discrimination problems (Sutherland and Rudy 1989;Whishaw and Tomie 1991;Alvarado and Rudy 1995). Thus, data from studies of anterograde amnesia after hippocampus damage support the conclusions that the hippocampus is not necessary for simple discrimination learning and that neural systems outside the hippocampus are capable of encoding, storing, and retrieving memories supporting simple discrimination learning.One might conclude from the foregoing that the learning systems that support simple discriminations also function