SEROTONIN REDUCES SYNAPTIC EXCITATION IN THE SUPERFICIAL MEDIAL ENTORHINAL CORTEX OF THE RAT VIA A PRESYNAPTIC MECHANISM

The superficial layers II and III of the entorhinal cortex, which form the main cortical input to the hippocampus, receive a large serotoner gic projection from the raphe nuclei and express 5-HT receptors at hig h density. Here, we studied the effects of serotonin on the intrinsic properties and excitatory synaptic transmission of the superficial med ial entorhind cortex. 2. Intracellular and patch clamp recordings reve aled that serotonin hyperpolarized only one-third of the cells, approx imately, through a potassium conductance via a GTP-dependent process. 3. Serotonin depressed mixed as well as isolated lpha-amino-3-hydroxy- 5-methyl-4-isoxazolepropionic acid receptor (AMPAR)- and N-methyl-D-as partic acid receptor (NMDAR)mediated excitatory postsynaptic potential s/currents (EPSPs/EPSCs; approximately 40% reduction with 1 mu m serot onin). 4. The effect of serotonin on EPSPs/EPSCs was similar in whole- cell versus intracellular recordings; it did not require intracellular GTP and was not visible in glutamate applications to excised patches. Miniature EPSCs recorded in the presence of tetrodotoxin and bicucull ine were reduced in frequency but not altered in amplitude. 5. The eff ects of serotonin on intrinsic properties and EPSPs were partially mim icked by 5-HT1A receptor agonists (+)-8-hydroxy-2-(di-n-propylamino)te tralin hydrobromide (8-OH-DPBT) and 5-carboxamido-tryptamine maleate ( 5-CT), and reduced by 5-HT1A receptor antagonists S-(-)-5-fluoro-8-hyd roxy-DPAT hydrochloride (S-UH-301), ethoxyphenyl)-4-[4-(2-phthalimido) butyl]piperazine hydrobromide (NAN-190) and spiperone. 6. We conclude that serotonin potently suppresses excitatory synaptic transmission vi a 5-HT1A receptors in layers II and III of the medial entorhinal corte x by a presynaptic mechanism.