Aging is associated with declining function across a broad spectrum of behavioral and biologicalmeasures. This component of the program project will pursue a combination of behavioral andneurophysiological studies aimed at characterizing the nature and range of alterations in neuronalrepresentations associated with aging:
Specific Aim 1 : Extending on findings of the previous funding period, we will examine the development ofnew hippocampal spatial representations when animals are presented with a novel environment. Ourprevious studies indicated that CAS neurons selectively are hyperactive and are 'rigid' in that they retrieveold representations rather than form new ones when experiencing a novel environment. These studies willexamine the relationship between hyperactivity and rigidity of CAS cells and memory performance, and willexamine the effects of putative memory enhancing drugs on hippocampal network activity.
Specific Aim 2 : Exploiting recent findings of hippocampal neuronal activity patterns closely associated withmemory performance in young animals, we will characterize the nature of performance-related abnormalitiesin hippocampal representation associated with aging. These studies will determine whether trial-by-trialmemory errors in a T-maze spatial delayed alternation task are associated with compromised stability ofhippocampal spatial representations, retrieval of inappropriate memory representations, or failure to encodeor retrieve trial specific representations. These studies will also examine the effects of putative memoryenhancing drugs on memory-related neural activity patterns.
Specific Aim 3 : We will use recently developed protocol for distinguishing 'recollection' and 'familiarity'components of recognition memory to examine the nature of age-related cognitive deficits in our rodentmodel. We will also compare performance related activation of areas of the prefrontal cortex andhippocampal region in encoding and retrieval and loss of functions in these areas associated with aging.These studies will also examine the effects of putative memory enhancing drugs on component processes inrecognition memory in aged rats.Each of these experiments is designed to test specific hypotheses about the nature of age-relatedcognitive decline and to identify and characterize pharmacological agents as targets of potential therapeuticvalue. Furthermore, comparisons of the results among these experiments, and with findings from the otherprojects, will identify features of cognitive aging and effects of therapeutic agents that are common or distinctacross a range of behavioral tasks.
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