Modulation by serotonin 5-HT(4) receptors of long-term potentiation and depotentiation in the dentate gyrus of freely moving rats.
Tetanization-induced long-term potentiation (LTP) in the hippocampus can be depotentiated by low-frequency stimulation. 5-HT(4) receptors are expressed in the hippocampus and are suggested to be involved in hippocampus-dependent cognitive processes. Since the role of these receptors in the dentate gyrus has yet not been characterized, this study investigated the effects of 5-HT(4) receptors on basal synaptic transmission, LTP and depotentiation in the dentate gyrus of freely moving rats. Male Wistar rats were chronically implanted with a recording electrode in the dentate gyrus granule cell layer, a stimulation electrode in the medial perforant path and a cannula for drug administration in the ipsilateral ventricle. The 5-HT(4) agonist methoxytryptamine dose-dependently inhibited basal synaptic transmission and LTP. Priming of receptors by a dose of this agonist which elicited no significant change of basal synaptic transmission inhibited depotentiation. These effects could be prevented by the 5-HT(4) antagonist RS 39604, which did not produce independent effects on synaptic transmission, LTP or depotentiation. The effects of methoxytryptamine were confirmed with the highly selective 5-HT(4) agonist, RS 67333. These results strongly support a role for 5-HT(4) receptors in hippocampal synaptic plasticity and provide an important link to findings with regard to the involvement of 5-HT in processes related to learning and memory.
Kulla
Alexander
A
Institute for Physiology of the Charite, Synaptic Plasticity Group, Humboldt University, Tucholskystrasse 2, D-10117 Berlin, Germany.
Manahan-Vaughan
Denise
D
D008735:5-Methoxytryptamine / Q000494:pharmacology; D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D018891:Dentate Gyrus / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D009043:Motor Activity; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism*; D044422:Receptors, Serotonin, 5-HT4; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000814:Aniline Compounds; D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044422:Receptors, Serotonin, 5-HT4; C107826:RS 67333; D008735:5-Methoxytryptamine