Serotonin 5-HT1A Receptor-Mediated Reduction of Excitatory Synaptic Transmission in Layers II/III of the Parasubiculum.

Neuroscience. 2019 May 15;406:325-332

Authors: Carter F, Chapman CA

Abstract

Serotonin (5-HT) has important effects on cognitive function within the hippocampal region where it modulates membrane potential and excitatory and inhibitory synaptic transmission. Here, we investigated how 5-HT modulates excitatory synaptic strength in layers II/III of the parasubiculum in rat brain slices. Bath-application of 1 or 10?µM 5-HT resulted in a strong, dose-dependent, and reversible reduction in the amplitude of field excitatory postsynaptic potentials (fEPSPs) recorded in the parasubiculum. The 5-HT reuptake blocker citalopram (10?µM) also reduced fEPSP amplitudes, indicating that 5-HT released within the slice inhibits synaptic transmission. The reduction of fEPSPs induced by 5-HT was blocked by the 5-HT1A receptor blocker NAN-190 (10?µM), but not by the 5-HT7 receptor blocker SB-269970 (10?µM). Moreover, the 5-HT1A agonist 8-OH-DPAT induced a reduction of fEPSP amplitude similar to that induced by 5-HT. The reduction was prevented by the 5-HT1A receptor blocker NAN-190. The reduction in fEPSPs induced by either 5-HT or by 8-OH-DPAT was accompanied by an increase in paired-pulse ratio, suggesting that it is due mainly to reduced glutamate release. Our data suggest that the effects of serotonin on cognitive function may depend in part upon a 5-HT1A-mediated reduction of excitatory synaptic transmission in the parasubiculum. This may also affect synaptic processing in the entorhinal cortex, which receives the major output projection of the parasubiculum.

PMID: 30902681 [PubMed - in process]