Over the past
two decades a number of myths about the aging brain and
about cognition in normal aging have been shattered. The
idea that there is mandatory widespread neuron loss or
dramatic cognitive deterioration during aging in healthy
individuals is clearly wrong. This is not to imply that
there are no changes in neurobiology or behavior over
the lifespan; rather, the neural alterations can be very
selective, and the cognitive changes subtle.
The study of
the hippocampus, and its role in certain forms of memory,
has been particularly fruitful in facilitating the understanding
of the neural mechanisms of memory in rats, monkeys, and
humans. In all these mammals, an intact hippocampus is
necessary for the ability to navigate in extended environments.
Healthy, older humans, monkeys, and rats all show poorer
spatial memory of this type, than do their younger counterparts.
A number of
laboratories, including ours, have conducted studies of
how the aging process affects cellular and molecular mechanisms
of synaptic plasticity and spatial memory in rats. These
experiments have provided a framework for understanding
how the brain stores and retrieves information and what
biological processes may underlie the cognitive changes
that are observed in mammals as they age. Alterations
in cell connectivity, and brain plasticity mechanisms
during aging are reviewed.
More recently
our research group has developed methods for recording
from many single neurons in freely behaving rats that
has provided an unprecedented window into changes in neural
population coding dynamics in the young and aged rodent
hippocampus in relation to spatial learning and memory.
With these methods we have discovered what appears to
be a principal neuronal population correlate of memory
retrieval failure in old rats. We propose that this age-related
change in the dynamics of neural coding may provide a
plausible explanation for why elderly people more frequently
become spatially disoriented or lost.
Finally, a
new anatomical method has just been discovered that is
able to detect whether single cells have been recently
active in a given behavioral experience. We believe that
this method has the potential to provide a bridge between
what is known about the activity characteristics of ensembles
of cells recorded during behavior, and what we know about
multiple genes that are activated during these behaviors.
It is possible now to envision whole brain imaging of
neuronal activity at the level of individual cells, using
multiple genes as markers, with discrete temporal resolution
of multiple experiences. This new cellular/molecular imaging
approach should complement existing functional imaging
methods, and should help achieve a more complete understanding
of the systems responsible for both normal cognitive processing
and the cognitive changes observed during aging.
