Activation of 5-HT7 receptors depresses excitatory synaptic transmission at parallel fiber-Purkinje cell synapses in mouse cerebellar cortex

The 5-HT7 receptor is the most recently identified member of the 5-HT receptor family. It is involved in the modulation of learning and memory processes and interacts with several signaling systems in the central nervous system including glutamate receptors. Since the cerebellum receives a rich serotoninergic innervation that originates in the reticular formation, we investigated the function and signaling properties of 5-HT7 receptors on the excitatory synapses received by Purkinje cells. We found that the activation of 5-HT7 by the selective agonist LP-211 (1 µM) produced an inhibitory effect on parallel fiber???evoked postsynaptic currents (EPSCs), that was prevented by the 5-HT7 receptor antagonist, SB-269970, but not by 5-HT1 receptor antagonist., WAY-100635. The decrease of glutamatergic response induced by LP was postsynaptically expressed, in accordance with the immunochemical localization of 5-HT7 at the Purkinje cell body and dendrites, and required the protein kinase A.EPSCs evoked by climbing fiber stimulation were not affected by LP. These results suggest the existence of a new mechanism of regulation allowing the serotonin afferents to refine the signals arriving to Purkinje cells during learning.