title: 5-HT4-receptors modulate induction of long-term depression but not potentiation at hippocampal output synapses in acute rat brain slices.
abstract: The subiculum is the principal target of CA1 pyramidal cells and mediates hippocampal output to various cortical and subcortical regions of the brain. The majority of subicular pyramidal cells are burst-spiking neurons. Previous studies indicated that high frequency stimulation in subicular burst-spiking cells causes presynaptic NMDA-receptor dependent long-term potentiation (LTP) whereas low frequency stimulation induces postsynaptic NMDA-receptor-dependent long-term depression (LTD). In the present study, we investigate the effect of 5-hydroxytryptamine type 4 (5-HT4) receptor activation and blockade on both forms of synaptic plasticity in burst-spiking cells. We demonstrate that neither activation nor block of 5-HT4 receptors modulate the induction or expression of LTP. In contrast, activation of 5-HT4 receptors facilitates expression of LTD, and block of the 5-HT4 receptor prevents induction of short-term depression and LTD. As 5-HT4 receptors are positively coupled to adenylate cyclase 1 (AC1), 5-HT4 receptors might modulate PKA activity through AC1. Since LTD is blocked in the presence of 5-HT4 receptor antagonists, our data are consistent with 5-HT4 receptor activation by ambient serotonin or intrinsically active 5-HT4 receptors. Our findings provide new insight into aminergic modulation of hippocampal output.
authors: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Berlin, Germany ; Institute of Neurophysiology, Charité Universitätsmedizin Berlin, Berlin, Berlin, Germany ; Exzellenzcluster NeuroCure, Charité Universitätsmedizin Berlin, Berlin, Berlin, Germany.
authors: Matthias
authors: M
authors: Wawra
authors: Department of Neurology, Charité Universitätsmedizin Berlin, Berlin, Berlin, Germany.
authors: Pawel
authors: P
authors: Fidzinski
authors: Institute of Neurophysiology, Charité Universitätsmedizin Berlin, Berlin, Berlin, Germany ; Exzellenzcluster NeuroCure, Charité Universitätsmedizin Berlin, Berlin, Berlin, Germany.
authors: Uwe
authors: U
authors: Heinemann
authors: Exzellenzcluster NeuroCure, Charité Universitätsmedizin Berlin, Berlin, Berlin, Germany ; Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors: Istvan
authors: I
authors: Mody
authors: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Berlin, Germany ; Institute of Neurophysiology, Charité Universitätsmedizin Berlin, Berlin, Berlin, Germany ; Department of Psychiatry, Psychotherapy and Psychosomatics, Ruppiner Kliniken, Neuruppin, Brandenburg, Germany.
authors: Joachim
authors: J
authors: Behr
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation; D036881:Long-Term Synaptic Depression; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044422:Receptors, Serotonin, 5-HT4 / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*
chemical_list: D044422:Receptors, Serotonin, 5-HT4