Reduction of GABAB inhibitory postsynaptic potentials by serotonin via pre‐ and postsynaptic mechanisms in CA3 pyramidal cells of rat hippocampus in vitro

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Abstract
The action of serotonin (5‐HT) on GABAergic synaptic transmission was investigated with intracellular recordings in CA3 pyramidal cells of rat hippocampal slices. Local application of 5‐HT (500 m̈M) hyperpolarized CA3 pyramidal cells, decreased cellular input resistance, and reduced slow afterhyperpolarizations. Serotonin attenuated the late (GABAB) component of polysynaptic inhibitory postsynaptic potentials (IPSPs; 47% of control) without affecting the early (GABAA) component. During bath application of the excitatory amino acid antagonists 6‐cyano‐7‐nitroquinoxaline‐2, 3‐di‐one (CNQX) (20 m̈M) and 2‐amino‐5‐phosphonovalerate (AP‐5) (40 m̈M), 5‐HT similarly decreased the amplitude of the late (GABAB) component (17% of control) of monosynaptic IPSPs but did not affect the early (GABAA) component. The mean reversal potentials of poly‐ and monosynaptic IPSPs were unaffected by 5‐HT. The conductance increases associated with the late component of poly‐ and monosynaptic IPSPs were reduced by 5‐HT. Hyperpolarizing responses evoked in CA3 pyramidal cells by somatic applications of gamma‐aminobutyric acid (GABA) were unaffected by 5‐HT. During bath application of bicuculline (20–50 m̈M), hyperpolarizing responses elicited by dendritic GABA application were reduced by 5‐HT (71% of control). The effect of 5‐HT on these direct GABAB hyperpolarizations (29% decrease in response) does not appear sufficient to fully account for the effect of 5‐HT on late GABAB IPSPs (53–83% decrease in response). Therefore, 5‐HT may reduce GABAB IPSPs in CA3 pyramidal cells 1) by a postsynaptic action on pyramidal cells and 2) by a selective presynaptic action on GABAergic interneurons mediating the GABAB IPSP. This presynaptic action of 5‐HT does not appear to involve excitatory afferents onto inhibitory interneurons.