NEURAL MECHANISMS OF COGNITIVE DECLINE IN SENESCENCE

My general research program is directed towards an understanding of the
electrophysiological, neurochemical and behavioral correlates of the
decline in spatial cognition and memory with age. The ultimate goal is
the development of preventative or ameliorative treatments for this
decline in mental health. The investigations focus on aging of the
rodent hippocampal system, including its intrinsic connections and
information processing characteristics, and those of its major cortical
and subcortical connections, in relation to the contribution that these
neural structures make to cognitive changes that occur in old age. The first experimental question concerns the degree to which the age-
related loss of spatial selectivity in hippocampal unit activity that we
have found might be accounted for by disruption in information
processing characteristics of its cortical afferent, and what the
consequence of this loss might be for information processing at neural
levels receiving hippocampal output. This problem will be addressed
using a new technique developed in this laboratory (the stereotrode)
that enables the simultaneous recording from several single neurons in
conscious animals moving freely in a spatially extended environment.
The second major question is whether information storage throughout the
lifespan results in a significant rearrangement in the statistical
distribution of connection strengths in old neurons, which might account
for the restriction in the range of behavioral adaptability of older
animals. The answer to this question requires the analysis of cellular
interactions at the level of single neurons rather than the population
techniques as employed in previous studies. The third major
experimental question concerns the possibility that modulatory
influences in the hippocampus from subcortical afferent systems change
with age, and contribute to the observed cognitive inactivation of
discrete subcortical projection nuclei in conscious young and old
animals.