Topographical Organization of M-Current on Dorsal and Median Raphe Serotonergic Neurons

Overview

Journal Front Cell Neurosci

Specialty Cell Biology

Date 2021 Mar 15

PMID 33716672

Authors

Tsogbadrakh Bayasgalan

Andrea Csemer

Adrienn Kovacs

Krisztina Pocsai

Balazs Pal

Affiliations

Soon will be listed here.

Abstract

Dorsal and median raphe nuclei (DR and MR, respectively) are members of the reticular activating system and play important role in the regulation of the sleep-wakefulness cycle, movement, and affective states. M-current is a voltage-gated potassium current under the control of neuromodulatory mechanisms setting neuronal excitability. Our goal was to determine the proportion of DR and MR serotonergic neurons possessing M-current and whether they are organized topographically. Electrophysiological parameters of raphe serotonergic neurons influenced by this current were also investigated. We performed slice electrophysiology on genetically identified serotonergic neurons. Neurons with M-current are located rostrally in the DR and dorsally in the MR. M-current determines firing rate, afterhyperpolarization amplitude, and adaptation index (AI) of these neurons, but does not affect input resistance, action potential width, and high threshold oscillations.These findings indicate that M-current has a strong impact on firing properties of certain serotonergic neuronal subpopulations and it might serve as an effective contributor to cholinergic and local serotonergic neuromodulatory actions.

References

Greenwood B, Foley T, Day H, Campisi J, Hammack S, Campeau S . Freewheel running prevents learned helplessness/behavioral depression: role of dorsal raphe serotonergic neurons. J Neurosci. 2003; 23(7):2889-98. PMC: 6742115. View

Okaty B, Freret M, Rood B, Brust R, Hennessy M, deBairos D . Multi-Scale Molecular Deconstruction of the Serotonin Neuron System. Neuron. 2015; 88(4):774-91. PMC: 4809055. DOI: 10.1016/j.neuron.2015.10.007. View

Monti J . Serotonin control of sleep-wake behavior. Sleep Med Rev. 2011; 15(4):269-81. DOI: 10.1016/j.smrv.2010.11.003. View

Koyama S, Appel S . Characterization of M-current in ventral tegmental area dopamine neurons. J Neurophysiol. 2006; 96(2):535-43. DOI: 10.1152/jn.00574.2005. View

Crawford L, Craige C, Beck S . Increased intrinsic excitability of lateral wing serotonin neurons of the dorsal raphe: a mechanism for selective activation in stress circuits. J Neurophysiol. 2010; 103(5):2652-63. PMC: 2867584. DOI: 10.1152/jn.01132.2009. View

Bordas C, Kovacs A, Pal B . The M-current contributes to high threshold membrane potential oscillations in a cell type-specific way in the pedunculopontine nucleus of mice. Front Cell Neurosci. 2015; 9:121. PMC: 4388076. DOI: 10.3389/fncel.2015.00121. View

Tzingounis A, Heidenreich M, Kharkovets T, Spitzmaul G, Jensen H, Nicoll R . The KCNQ5 potassium channel mediates a component of the afterhyperpolarization current in mouse hippocampus. Proc Natl Acad Sci U S A. 2010; 107(22):10232-7. PMC: 2890451. DOI: 10.1073/pnas.1004644107. View

Kharkovets T, Hardelin J, Safieddine S, Schweizer M, El-Amraoui A, Petit C . KCNQ4, a K+ channel mutated in a form of dominant deafness, is expressed in the inner ear and the central auditory pathway. Proc Natl Acad Sci U S A. 2000; 97(8):4333-8. PMC: 18242. DOI: 10.1073/pnas.97.8.4333. View

Ren J, Friedmann D, Xiong J, Liu C, Ferguson B, Weerakkody T . Anatomically Defined and Functionally Distinct Dorsal Raphe Serotonin Sub-systems. Cell. 2018; 175(2):472-487.e20. PMC: 6173627. DOI: 10.1016/j.cell.2018.07.043. View

10.

Hornung J . The human raphe nuclei and the serotonergic system. J Chem Neuroanat. 2004; 26(4):331-43. DOI: 10.1016/j.jchemneu.2003.10.002. View

11.

Baksa B, Kovacs A, Bayasgalan T, Szentesi P, Koszeghy A, Szucs P . Characterization of functional subgroups among genetically identified cholinergic neurons in the pedunculopontine nucleus. Cell Mol Life Sci. 2019; 76(14):2799-2815. PMC: 6588655. DOI: 10.1007/s00018-019-03025-4. View

12.

Ren J, Isakova A, Friedmann D, Zeng J, Grutzner S, Pun A . Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei. Elife. 2019; 8. PMC: 6812963. DOI: 10.7554/eLife.49424. View

13.

Marrion N . Control of M-current. Annu Rev Physiol. 1997; 59:483-504. DOI: 10.1146/annurev.physiol.59.1.483. View

14.

Roepke T, Smith A, Ronnekleiv O, Kelly M . Serotonin 5-HT2C receptor-mediated inhibition of the M-current in hypothalamic POMC neurons. Am J Physiol Endocrinol Metab. 2012; 302(11):E1399-406. PMC: 3378066. DOI: 10.1152/ajpendo.00565.2011. View

15.

Graeff F, Guimaraes F, de Andrade T, Deakin J . Role of 5-HT in stress, anxiety, and depression. Pharmacol Biochem Behav. 1996; 54(1):129-41. DOI: 10.1016/0091-3057(95)02135-3. View

16.

Zhao C, Su M, Wang Y, Li X, Zhang Y, Du X . Selective Modulation of K Channel Kv7.4 Significantly Affects the Excitability of DRN 5-HT Neurons. Front Cell Neurosci. 2018; 11:405. PMC: 5735115. DOI: 10.3389/fncel.2017.00405. View

17.

Brown D, Passmore G . Neural KCNQ (Kv7) channels. Br J Pharmacol. 2009; 156(8):1185-95. PMC: 2697739. DOI: 10.1111/j.1476-5381.2009.00111.x. View

18.

Huang H, Trussell L . KCNQ5 channels control resting properties and release probability of a synapse. Nat Neurosci. 2011; 14(7):840-7. PMC: 3133966. DOI: 10.1038/nn.2830. View

19.

Hale M, Lowry C . Functional topography of midbrain and pontine serotonergic systems: implications for synaptic regulation of serotonergic circuits. Psychopharmacology (Berl). 2010; 213(2-3):243-64. DOI: 10.1007/s00213-010-2089-z. View

20.

Andrade R, Haj-Dahmane S . Serotonin neuron diversity in the dorsal raphe. ACS Chem Neurosci. 2013; 4(1):22-5. PMC: 3547477. DOI: 10.1021/cn300224n. View