The 5-HT3 receptor is a ligand-gated ion channel activated by serotonin.
Although originally identified in the peripheral nervous system, the 5-HT3 receptor is also ubiquitously expressed in the central nervous system. Sites of expression include several brain stem nuclei, as well as higher cortical areas such as amygdala, hippocampus and cortex. On the subcellular level, both presynaptic and postsynaptic 5-HT3 receptors can be found.
Presynaptic 5-HT3 receptors are involved in mediating, or modulating, neurotransmitter release. Postsynaptic 5-HT3 receptors are preferentially expressed on interneurons. Recently, in collaboration with the group of Prof. Monyer in Heidelberg, Germany, we have developed a transgenic mouseline in which EGFP is expressed under the control of the 5-HT3A promotor, enabeling the direct identification of 5-HT3 receptor-expressing neurons in living tissue.
Dr J.A. van Hooft
Cajal-Retzius cells express 5-HT3 receptors.
(A) Expression of EGFP (Ai) and reelin (Aii) in saggital sections of the cortex of 5-HT3A/EGFP mice at P0, shown at low magnification.
(B) Saggital sections of the cortex taken from 5-HT3A/EGFP mice at P0, showing expression of
EGFP (Bi), of reelin (Bii) and the co-expression (Biii).
Arrows indicate cells that co-express EGFP and reelin.
(C) Biocytin-filled EGFP-positive cell in layer I of the cortex showing the typical morphology of a Cajal-Retzius cell.
(D) Whole-cell patch clamp recordings of 5-HT3 receptor-mediated currents under voltage clamp (left trace) and 5-HT3 receptor-mediated depolarization under current clamp (right trace) by electrical stimulation of layer I. Bath application of 25 nM tropisetron resulted in a complete block of the 5-HT3 receptor-mediated synaptic current (red trace). Arrows indicate the stimulation artefact.
Using this mouseline, we focus our attention on stuying the physiological role of 5-HT3 receptors in the central nervous system. At the moment, we investigate
In our lab, we use a wide array of methodologies, as imposed by the questions that need to be answered. Our expertise is in (patch clamp) electrophysiology, but we also use imaging-, staining-, behavioural-, moleculair biological- and biochemical techniques to meet our needs.
Chameau, P., Inta, D., Vitalis, T., Monyer, H., Wadman, W.J. and van Hooft, J.A. (2009)
The N-terminal fragment of reelin controls postnatal dendritic maturation of cortical pyramidal neurons.
Proceedings of the National Academy of Sciences U.S.A., 106, 7227-7232 .
Smit-Rigter LA, Champagne DL, van Hooft JA (2009)
Lifelong impact of variations in maternal care on dendritic structure and function
of cortical layer 2/3 pyramidal neurons in rat offspring
PLoS One 4:e5167
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Inta, D., Alfonso, J., von Engelhardt, J., Kreuzberg, M., Meyer, A.H., van Hooft
and Monyer, H. (2008)
Neurogenesis and widespread forebrain migration of distinct GABAergic neurons from the postnatal subventricular zone.
Proceedings of the National Academy of Sciences U.S.A., 105, 20994-20999
Chameau, P. and van Hooft, J.A. (2006)
Serotonin 5-HT3 receptors in the central nervous system.
Cell & Tissue Research, 326, 573-581
van Hooft, J.A. and Yakel, J.L. (2003)
5-HT3 receptors in the CNS: 3b or not 3b?
Trends in Pharmacological Sciences, 24, 157-160
van Hooft, J.A. and Wadman, W.J. (2003)
Ca2+ ions block and permeate serotonin 5-HT3 receptor channels in rat hippocampal interneurons
Journal of Neurophysiology, 89, 1864-1869
Sudweeks, S.N., van Hooft, J.A. and Yakel, J.L. (2002)
Serotonin 5-HT3 receptors in rat CA1 hippocampal interneurons:
functional and molecular characterization
Journal of Physiology, 544, 715-726
van Hooft, J.A. and Vijverberg, H.P.M. (2000)
5-HT3 receptors and neurotransmitter release in the CNS: a nerve ending story?
Trends in Neurosciences, 23, 605-610
van Hooft, J.A., Spier, A.D., Yakel, J.L., Lummis, S.C.R. and Vijverberg, H.P.M. (1998)
Promiscuous coassembly of serotonin 5-HT3 and nicotinic ?4 receptor subunits into Ca2+
permeable ion channels
Proceedings of the National Academy of Sciences U.S.A., 95, 11456-11461
This page was last updated on 11 march 2010