Serotonin regulates synaptic connections in the dentate molecular layer of adult rats via 5-HT1a receptors: evidence for a glial mechanism.

The present study sought to verify effects of 5-HT on synaptic density at the ultrastructural level, to determine whether the 5-HT1a receptor is important for the maintenance of synaptic connections and to obtain evidence implicating S100 beta in the apparent neurotrophic actions of 5-HT. Reduction of hippocampal 5-HT with para-chloroamphetamine (PCA) resulted in a significant decline in the synaptic density of the dentate molecular layer. Reduction of norepinephrine with DSP-4 produced a slight decrease in the number of molecular layer synapses, but this difference was not statistically different from control values. 5-HT1a antagonist treatment resulted in a decline in synaptic density comparable to that observed following PCA treatment. These observations suggest that 5-HT functions to maintain synaptic connections in the dentate molecular layer via a 5-HT1a mechanism. To determine whether the change in synaptic density was due to the action of 5-HT on neuronal receptors or astrocytic receptors, a monoclonal antibody against S100 beta was infused into the lateral ventricle for seven days. Controls received infusions of normal goat serum. Half of the rats from the anti-S100 beta and control groups also received daily injections of NAN-190. Anti-S100 beta infusion resulted in a significant (p < 0.01) decrease in synapses compared to serum controls. Concomitant NAN-190 administration did not enhance synapse loss in the anti-S100 beta group. The results of this study suggest that the maintenance of synaptic connections in the dentate molecular layer is influenced by S100 beta levels that are controlled by 5-HT stimulation of astrocytic 5-HT1a receptors.