Serotonin Regulates the Firing of Principal Cells of the Subiculum by Inhibiting a T-type Ca Current

Overview

Journal Front Cell Neurosci

Specialty Cell Biology

Date 2017 Mar 23

PMID 28326015

Citations 15

Authors

Anders V Petersen

Camilla S Jensen

Valerie Crepel

Mathias Falkerslev

Jean-Francois Perrier

Affiliations

Soon will be listed here.

Abstract

The subiculum is the main output of the hippocampal formation. A high proportion of its principal neurons fire action potentials in bursts triggered by the activation of low threshold calcium currents. This firing pattern promotes synaptic release and regulates spike-timing-dependent plasticity. The subiculum receives a high density of fibers originating from the raphe nuclei, suggesting that serotonin (5-HT) modulates subicular neurons. Here we investigated if and how 5-HT modulates the firing pattern of bursting neurons. By combining electrophysiological analysis with pharmacology, optogenetics and calcium imaging, we demonstrate that 5-HT receptors reduce bursting activity by inhibiting a low-threshold calcium current mediated by T-type Ca channels in principal cells of the subiculum. In addition, we show that the activation of this novel pathway decreases bursting activity and the occurrence of epileptiform discharges induced in models for temporal lobe epilepsy (TLE).

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References

Applegate C, Tecott L . Global increases in seizure susceptibility in mice lacking 5-HT2C receptors: a behavioral analysis. Exp Neurol. 1999; 154(2):522-30. DOI: 10.1006/exnr.1998.6901. View

Pisani F, Spina E, Oteri G . Antidepressant drugs and seizure susceptibility: from in vitro data to clinical practice. Epilepsia. 1999; 40 Suppl 10:S48-56. DOI: 10.1111/j.1528-1157.1999.tb00885.x. View

Bloom S, Edwards A, Garrett J . Effects of stimulating the sympathetic innervation in bursts on submandibular vascular and secretory function in cats. J Physiol. 1987; 393:91-106. PMC: 1192382. DOI: 10.1113/jphysiol.1987.sp016812. View

Sharp P, Green C . Spatial correlates of firing patterns of single cells in the subiculum of the freely moving rat. J Neurosci. 1994; 14(4):2339-56. PMC: 6577112. View

Kondziella D, Asztely F . Don't be afraid to treat depression in patients with epilepsy!. Acta Neurol Scand. 2008; 119(2):75-80. DOI: 10.1111/j.1600-0404.2008.01088.x. View

Patterson K, Baram T, Shinnar S . Origins of temporal lobe epilepsy: febrile seizures and febrile status epilepticus. Neurotherapeutics. 2014; 11(2):242-50. PMC: 3996115. DOI: 10.1007/s13311-014-0263-4. View

Llinas R, Yarom Y . Properties and distribution of ionic conductances generating electroresponsiveness of mammalian inferior olivary neurones in vitro. J Physiol. 1981; 315:569-84. PMC: 1249399. DOI: 10.1113/jphysiol.1981.sp013764. View

Zhao S, Ting J, Atallah H, Qiu L, Tan J, Gloss B . Cell type–specific channelrhodopsin-2 transgenic mice for optogenetic dissection of neural circuitry function. Nat Methods. 2011; 8(9):745-52. PMC: 3191888. DOI: 10.1038/nmeth.1668. View

Harris E, Stewart M . Propagation of synchronous epileptiform events from subiculum backward into area CA1 of rat brain slices. Brain Res. 2001; 895(1-2):41-9. DOI: 10.1016/s0006-8993(01)02023-6. View

10.

Favale E, Audenino D, Cocito L, Albano C . The anticonvulsant effect of citalopram as an indirect evidence of serotonergic impairment in human epileptogenesis. Seizure. 2003; 12(5):316-8. DOI: 10.1016/s1059-1311(02)00315-1. View

11.

Rosenstein D, Nelson J, Jacobs S . Seizures associated with antidepressants: a review. J Clin Psychiatry. 1993; 54(8):289-99. View

12.

OMara S, Commins S, Anderson M, Gigg J . The subiculum: a review of form, physiology and function. Prog Neurobiol. 2001; 64(2):129-55. DOI: 10.1016/s0301-0082(00)00054-x. View

13.

Yan Q, Jobe P, Cheong J, Ko K, Dailey J . Role of serotonin in the anticonvulsant effect of fluoxetine in genetically epilepsy-prone rats. Naunyn Schmiedebergs Arch Pharmacol. 1994; 350(2):149-52. DOI: 10.1007/BF00241089. View

14.

Faas G, Vreugdenhil M, Wadman W . Calcium currents in pyramidal CA1 neurons in vitro after kindling epileptogenesis in the hippocampus of the rat. Neuroscience. 1996; 75(1):57-67. DOI: 10.1016/0306-4522(96)00254-0. View

15.

Knopp A, Frahm C, Fidzinski P, Witte O, Behr J . Loss of GABAergic neurons in the subiculum and its functional implications in temporal lobe epilepsy. Brain. 2008; 131(Pt 6):1516-27. DOI: 10.1093/brain/awn095. View

16.

Buchanan G, Murray N, Hajek M, Richerson G . Serotonin neurones have anti-convulsant effects and reduce seizure-induced mortality. J Physiol. 2014; 592(19):4395-410. PMC: 4215784. DOI: 10.1113/jphysiol.2014.277574. View

17.

Jung H, Staff N, Spruston N . Action potential bursting in subicular pyramidal neurons is driven by a calcium tail current. J Neurosci. 2001; 21(10):3312-21. PMC: 6762486. View

18.

Becker A, Pitsch J, Sochivko D, Opitz T, Staniek M, Chen C . Transcriptional upregulation of Cav3.2 mediates epileptogenesis in the pilocarpine model of epilepsy. J Neurosci. 2008; 28(49):13341-53. PMC: 6671595. DOI: 10.1523/JNEUROSCI.1421-08.2008. View

19.

Wenger G, Stitzel R, Craig C . The role of biogenic amines in the reserpine-induced alteration of minimal electroshock seizure thresholds in the mouse. Neuropharmacology. 1973; 12(7):693-703. DOI: 10.1016/0028-3908(73)90122-6. View

20.

Oleskevich S, Descarries L . Quantified distribution of the serotonin innervation in adult rat hippocampus. Neuroscience. 1990; 34(1):19-33. DOI: 10.1016/0306-4522(90)90301-j. View