Age-related decrease in cholinergic synaptic transmission in three hippocampal subfields.

The present study was designed to examine the effect of age on cholinergic synaptic transmission in the three principal hippocampal subregions, and to assess whether these effects covary with age-related behavioral deficits. Young (3 week), adult (9 month), and old (24-27 month) rats were first tested on the Morris water task, and most of the old rats were severely impaired on the spatial version. The cholinergic slow epsp was induced by tetanic stimulation of stratum oriens or stratum granulosum, and recorded intracellularly in vitro from CA1 and CA3 pyramidal cells and granule cells in the fascia dentata (FD). The amplitude of the slow epsp was significantly reduced in old rats in all areas (CA1 59%; CA3 55%; and FD 56%). This age-related decrease was also present following the blockade of glutamatergic and GABAergic transmission, ruling out possible artifactual contributions from these systems to the change in the slow epsp. Our data suggest that functional cholinergic transmission is compromised in all areas of the hippocampus during normal aging. Few statistically significant correlations, however, were found between the age-related deficit in spatial learning and the decrease in cholinergic synaptic function.