Synaptogenesis in the postnatal rat fascia dentata is influenced by 5-HT1a receptor activation.

Neonatal serotonin (5-HT) depletion or 5-HT1a receptor blockade results in a significant and permanent reduction in the number of dentate granule cell dendritic spines. The purpose of this study was to determine whether the loss of spines was accompanied by a reduction in molecular layer synaptic profile density. Rat pups were treated with parachloroamphetamine (PCA), 5,7-DHT or the 5-HT1a receptor antagonist NAN-190. The synaptic profile density (profiles/100 microm2) of the dentate molecular layer was estimated on P14, P21 and P60. Molecular layer synaptic profile density the was significantly reduced in each treatment group on P14 and P21. By P60, the NAN-190 and PCA groups had reached control values, but the 5,7-DHT group remained significantly lower than control. The most dramatic changes were observed among synapses terminating on dendritic spines. Numbers of profiles forming simple spine contacts were significantly reduced by all treatments at P14 and P21, but returned to normal by P60 in the PCA and NAN-190 groups. Simple spine synapses in the 5,7-DHT group remained significantly below control, but numbers of complex spine synapses were higher than either control or the other treatment groups at each age. These results indicate that the loss of dendritic spines observed following 5-HT depletion or 5-HT1a antagonist treatment is accompanied by a decrease in synaptic profile density. This effect appears to be a retardation of synaptogenesis since recovery occurs once 5-HT1a receptor activity resumes. Data from the 5,7-DHT group shows that complex spine synapse formation may represent an effort to attain some degree of functional compensation when synaptogenesis is slowed.