Serotonergic function of aging hippocampal CA3 pyramidal neurons: Electrophysiological assessment following administration of 5,7-dihydroxytryptamine in the fimbria-fornix and cingulum bundle

Serotonergic (5-hydroxytryptamine; 5-HT) neurotransmission has been implicated in the regulation of cognitive function and this neurotransmitter system may underlie selective neuronal degeneration found in the aging hippocampus. Age-dependent changes in 5-HT function of hippocampal CA3 subfield pyramidal neurons were evaluated in female Fischer 344 rats (2 and 17 months) following denervation of the serotonergic afferents to the dorsal hippocampus using the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). Vehicle (ascorbic saline) or 5,7-DHT was administered bilaterally in the fimbria-fornix/cingulum bundle and dorsal pyramidal cell responses to microiontophoretic application of 5-HT, the 5-HT1A agonist (+/-)-8-hydroxy-2-(di-N-propylamino) tetralin, the 5-HT1A antagonist WAY 100,135 and N-methyl-D-aspartate were recorded at 3 weeks post-lesion. Independent of changes in sensitivity to the inhibitory effects of 5-HT with aging, the time to recovery of cell firing following application of 5-HT was significantly increased in the 18 months 5,7-DHT group compared to the 18 month Vehicle and 3 month 5,7-DHT groups (3.3- and 2.6-fold, respectively). These results demonstrate that serotonergic neurotransmission is altered with aging following a selective neurotoxic insult to the hippocampus.