Carol A. Barnes, PhD
Psychology and Neurology
Director, Evelyn F. McKnight Brain Institute
University of Arizona
May 18, 2009
Brain and Behavioral Aging: Molecules, Maps and Memory
The work in the Barnes laboratory epitomizes the theme of this year’s Bauer Series: connections. Although adult aging can be accompanied by some degree of loss in neuronal mass, we now know that a significant contributor to age-related cognitive change lies not in the loss of cells but in changes in synaptic strength and thus neural connectivity. Dr. Barnes has been at the forefront of research in understanding the physiological processes that underlie the cognitive changes that occur in normal aging. We were honored to have her as one of our two M. R. Bauer Distinguished Lecturers.
Aging is associated with specific impairments of learning and memory, some of which are similar to those caused by damage to the area of the brain known as the hippocampus. For example, healthy older humans, monkeys, and rats all show poorer hippocampal-dependent spatial memory than do their younger counterparts.
The search for the underlying neurobiological changes responsible for these cognitive deficits have revealed that, in fact, many biological properties of old rat hippocampal cells are quite intact, and that there is stability in hippocampal principal cell number across aging in old humans and monkeys, as well as rodents. While widespread deterioration does not occur, selective anatomical and electrophysiological changes have been found. Smaller subregions of the hippocampal cells such as the dentate gyrus and CA1 sustain either a loss in the number or a loss of the function of synapses in aged, memory-impaired rats.
The changes in connectivity of the hippocampal region during aging have been thought to contribute to observed age-related impairments of synaptic plasticity, which include the observations that long-term potentiation (LTP) is more difficult to induce in older rats, and the synaptic weights decay about twice as fast in older as in younger animals. Moreover, long-term depression and the LTP reversal are both easier to induce in aged animals. Thus, a reasonable summary in terms of the effect of normative aging processes on hippocampal plasticity mechanisms is that the balance of increasing and decreasing synaptic weights through artificial stimulation is altered during aging, possibly contributing to the observed memory impairments in older animals. Consistent with this, Dr. Barnes discussed data that indicate that the transcription of immediate early gene markers of activity and plasticity (e.g., Arc) are reduced in old hippocampal cells following behavior.
The dynamic interactions among cells in hippocampal networks are also disrupted in aged rats, as measured during ensemble recordings in freely behaving animals. These studies have demonstrated that old rats have difficulty retrieving previous representations of well-learned environments, show defective behaviorally induced place field expansion plasticity, and deficits in reactivation of experiences during sleep with preserved temporal order. Taken together, the data suggest age-related impairments in storage, retrieval, and consolidation of information. Dr. Barnes concluded her presentation by describing experiments that highlighted the specificity of changes in the aged hippocampus, pointing to the dentate gyrus in rats and monkeys as being particularly vulnerable in normal aging, a pattern that is quite distinct from that observed in Alzheimer’s disease.