dopamine neuron; action potential; substantia nigra
Abstract :
[en] In many neuronal types, axon initial segment (AIS) geometry critically influences neuronal excitability. Interestingly, the axon of rat substantia nigra pars compacta (SNc) dopaminergic (DA) neurons displays a highly variable location and most often arises from an axon-bearing dendrite (ABD). We combined current-clamp somatic and dendritic recordings, outside-out recordings of dendritic sodium and potassium currents, morphological reconstructions and multi-compartment modelling on male and female rat SNc DA neurons to determine cell-to-cell variations in AIS and ABD geometry and their influence on neuronal output (spontaneous pacemaking frequency, AP shape). Both AIS and ABD geometries were found to be highly variable from neuron to neuron. Surprisingly, we found that AP shape and pacemaking frequency were independent of AIS geometry. Modelling realistic morphological and biophysical variations clarify this result: in SNc DA neurons, the complexity of the ABD combined with its excitability predominantly define pacemaking frequency and AP shape, such that large variations in AIS geometry negligibly affect neuronal output, and are tolerated.
Research Center/Unit :
Giga-Neurosciences - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Moubarak, Estelle
Engel, Dominique ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Pharmacologie
Dufour, Martial
Tapia, Monica
Tell, Fabien
Goaillard, Jean-Marc
Language :
English
Title :
Robustness to axon initial segment variation is explained by somatodendritic excitability in rat substantia nigra dopaminergic neurons
Publication date :
26 June 2019
Journal title :
Journal of Neuroscience
ISSN :
0270-6474
eISSN :
1529-2401
Publisher :
Society for Neuroscience, United States
Volume :
39
Issue :
26
Pages :
5044-5063
Peer reviewed :
Peer Reviewed verified by ORBi
European Projects :
FP7 - 616827 - CANALOHMICS - Biophysical networks underlying the robustness of neuronal excitability
Funders :
ANR - Agence Nationale de la Recherche [FR] CE - Commission Européenne [BE]
Amendola J, Woodhouse A, Martin-Eauclaire MF, Goaillard JM (2012) Ca(2)(+)/cAMP-sensitive covariation of I(A) and I(H) voltage dependences tunes rebound firing in dopaminergic neurons. J Neurosci 32: 2166 -2181.
Bean BP (2007) The action potential in mammalian central neurons. Nat Rev Neurosci 8: 451-465.
Bischofberger J, Jonas P (1997) Action potential propagation into the presynaptic dendrites of rat mitral cells. J Physiol 504: 359 -365.
Cajal SR (1952) Histologie du systeme nerveux de l’homme and des vertebres: Consejo Superior de Investigaciones Científicas. Madrid: Instituto Ramón y Cajal.
Carnevale NT, Hines ML (2006) The NEURON book: Cambridge: Cambridge UP.
Chan CS, Guzman JN, Ilijic E, Mercer JN, Rick C, Tkatch T, Meredith GE, Surmeier DJ (2007) ‘Rejuvenation’ protects neurons in mouse models of Parkinson’s disease. Nature 447: 1081-1086.
Chand AN, Galliano E, Chesters RA, GrubbMS (2015) A distinct subtype of dopaminergic interneuron displays inverted structural plasticity at the axon initial segment. J Neurosci 35: 1573-1590.
Chklovskii DB (2000) Optimal sizes of dendritic and axonal arbors in a topographic projection. J Neurophysiol 83: 2113-2119.
Clark BD, Goldberg EM, Rudy B (2009) Electrogenic tuning of the axon initial segment. Neuroscientist 15: 651-668.
Coombs JS, Curtis DR, Eccles JC (1957) The generation of impulses in motoneurones. J Physiol 139: 232-249.
Cuntz H, Borst A, Segev I (2007) Optimization principles of dendritic structure. Theor Biol Med Model 4: 21.
Debanne D, Campanac E, Bialowas A, Carlier E, Alcaraz G (2011) Axon physiology. Physiol Rev 91: 555-602.
Destexhe A, Babloyantz A, Sejnowski TJ (1993) Ionic mechanisms for intrinsic slow oscillations in thalamic relay neurons. Biophys J 65: 1538-1552.
Ding S, Wei W, Zhou FM (2011a) Molecular and functional differences in voltage-activated sodium currents between GABA projection neurons and dopamine neurons in the substantia nigra. J Neurophysiol 106: 3019-3034.
Ding S, Matta SG, Zhou FM (2011b) Kv3-like potassium channels are required for sustained high-frequency firing in basal ganglia output neurons. J Neurophysiol 105: 554 -570.
Drion G, Massotte L, Sepulchre R, Seutin V (2011) How modeling can reconcile apparently discrepant experimental results: the case of pacemaking in dopaminergic neurons. PLoS Comput Biol 7: e1002050.
Dufour MA, Woodhouse A, Amendola J, Goaillard JM (2014) Non-linear developmental trajectory of electrical phenotype in rat substantia nigra pars compacta dopaminergic neurons. Elife. Advance online publication. Retrieved October 20, 2014. doi: 10.7554/eLife.04059.
Engel D, SeutinV (2015) High dendritic expression of Ih in the proximity of the axon origin controls the integrative properties of nigral dopamine neurons. J Physiol 593: 4905-4922.
Fried SI, Lasker AC, Desai NJ, Eddington DK, Rizzo JF 3rd (2009) Axonal sodium-channel bands shape the response to electric stimulation in retinal ganglion cells. J Neurophysiol 101: 1972-1987.
Gantz SC, Ford CP, Morikawa H, Williams JT (2018) The evolving under-standing of dopamine neurons in the substantia nigra and ventral tegmental area. Annu Rev Physiol 80: 219 -241.
Gentet LJ, Williams SR (2007) Dopamine gates action potential backpropagation in midbrain dopaminergic neurons. J Neurosci 27: 1892-1901.
González-Cabrera C, Meza R, Ulloa L, Merino-Sepúlveda P, Luco V, Sanhueza A, Oñate-Ponce A, Bolam JP, Henny P (2017) Characterization of the axon initial segment of mice substantia nigra dopaminergic neurons. J Comp Neurol 525: 3529 -3542.
Grace AA, Bunney BS (1983) Intracellular and extracellular electrophysiology of nigral dopaminergic neurons: 2. Action potential generating mechanisms and morphological correlates. Neuroscience 10: 317-331.
Grace AA, Bunney BS (1984) The control of firing pattern in nigral dopamine neurons: single spike firing. J Neurosci 4: 2866 -2876.
Grace AA, Onn SP (1989) Morphology and electrophysiological properties of immunocytochemically identified rat dopamine neurons recorded in vitro. J Neurosci 9: 3463-3481.
Grubb MS, Burrone J (2010) Activity-dependent relocation of the axon initial segment fine-tunes neuronal excitability. Nature 465: 1070 -1074.
Gutzmann A, Ergül N, Grossmann R, Schultz C, Wahle P, Engelhardt M (2014) A period of structural plasticity at the axon initial segment in developing visual cortex. Front Neuroanat 8: 11.
Guzman JN, Sánchez-Padilla J, Chan CS, Surmeier DJ (2009) Robust pacemaking in substantia nigra dopaminergic neurons. J Neurosci 29: 11011-11019.
Hamada MS, Goethals S, de Vries SI, Brette R, KoleMH (2016) Covariation of axon initial segment location and dendritic tree normalizes the somatic action potential. Proc Natl Acad Sci U S A 113: 14841-14846.
Häusser M, Stuart G, Racca C, Sakmann B (1995) Axonal initiation and active dendritic propagation of action potentials in substantia nigra neurons. Neuron 15: 637-647.
Hay E, Schürmann F, Markram H, Segev I (2013) Preserving axosomatic spiking features despite diverse dendritic morphology. J Neurophysiol 109: 2972-2981.
Hesse J, Schreiber S (2015) Externalization of neuronal somata as an evolutionary strategy for energy economization. Curr Biol 25: R324 -R325.
Hines ML, Carnevale NT (1997) The NEURON simulation environment. Neural Comput 9: 1179 -1209.
Hines ML, Carnevale NT (2001) NEURON: a tool for neuroscientists. Neuroscientist 7: 123-135.
Hu W, Tian C, Li T, Yang M, Hou H, Shu Y (2009) Distinct contributions of Na(v)1.6 and Na(v)1.2 in action potential initiation and backpropagation. Nat Neurosci 12: 996 -1002.
Jang J, Um KB, Jang M, Kim SH, Cho H, Chung S, Kim HJ, Park MK (2014) Balance between the proximal dendritic compartment and the soma determines spontaneous firing rate in midbrain dopamine neurons. J Physiol 592: 2829 -2844.
Kole MH, Brette R (2018) The electrical significance of axon location diversity. Curr Opin Neurobiol 51: 52-59.
Kole MH, Stuart GJ (2012) Signal processing in the axon initial segment. Neuron 73: 235-247.
KoleMH,Ilschner SU, Kampa BM, Williams SR, Ruben PC, Stuart GJ (2008) Action potential generation requires a high sodium channel density in the axon initial segment. Nat Neurosci 11: 178 -186.
Kress GJ, Dowling MJ, Meeks JP, Mennerick S (2008) High threshold, proximal initiation, and slow conduction velocity of action potentials in dentate granule neuron mossy fibers. J Neurophysiol 100: 281-291.
Kress GJ, Dowling MJ, Eisenman LN, Mennerick S (2010) Axonal sodium channel distribution shapes the depolarized action potential threshold of dentate granule neurons. Hippocampus 20: 558 -571.
Kuba H (2012) Structural tuning and plasticity of the axon initial segment in auditory neurons. J Physiol 590: 5571-5579.
Kuba H, Ishii TM, OhmoriH (2006) Axonal site of spike initiation enhances auditory coincidence detection. Nature 444: 1069 -1072.
Kuba H, Adachi R, Ohmori H (2014) Activity-dependent and activityindependent development of the axon initial segment. J Neurosci 34: 3443-3453.
Kuznetsova AY, Huertas MA, Kuznetsov AS, Paladini CA, Canavier CC (2010) Regulation of firing frequency in a computational model of a midbrain dopaminergic neuron. J Comput Neurosci 28: 389-403.
Lezmy J, Lipinsky M, Khrapunsky Y, Patrich E, Shalom L, Peretz A, Fleidervish IA, Attali B (2017) M-current inhibition rapidly induces a unique CK2-dependent plasticity of the axon initial segment. Proc Natl Acad Sci U S A 114: E10234-E10243.
Lien CC, Jonas P (2003) Kv3 potassium conductance is necessary and kinetically optimized for high-frequency action potential generation in hippocampal interneurons. J Neurosci 23: 2058 -2068.
Liss B, Roeper J (2008) Individual dopamine midbrain neurons: functional diversity and flexibility in health and disease. Brain Res Rev 58: 314 -321.
Longair MH, Baker DA, Armstrong JD (2011) Simple neurite tracer: open source software for reconstruction, visualization and analysis of neuronal processes. Bioinformatics 27: 2453-2454.
Lorincz A, Nusser Z (2008) Cell-type-dependent molecular composition of the axon initial segment. J Neurosci 28: 14329 -14340.
Lorincz A, Nusser Z (2010) Molecular identity of dendritic voltage-gated sodium channels. Science 328: 906 -909.
Mainen ZF, Sejnowski TJ (1996) Influence of dendritic structure on firing pattern in model neocortical neurons. Nature 382: 363-366.
Mainen ZF, Carnevale NT, Zador AM, Claiborne BJ, Brown TH (1996) Electrotonic architecture of hippocampal CA1 pyramidal neurons based on three-dimensional reconstructions. J Neurophysiol 76: 1904 -1923.
Martina M, Vida I, Jonas P (2000) Distal initiation and active propagation of action potentials in interneuron dendrites. Science 287: 295-300.
Matsuda W, Furuta T, Nakamura KC, Hioki H, Fujiyama F, Arai R, Kaneko T (2009) Single nigrostriatal dopaminergic neurons form widely spread and highly dense axonal arborizations in the neostriatum. J Neurosci 29: 444-453.
Matsuda Y, Fujimura K, Yoshida S (1987) Two types of neurons in the substantia nigra pars compacta studied in a slice preparation. Neurosci Res 5: 172-179.
Meeks JP, Mennerick S (2007) Action potential initiation and propagation in CA3 pyramidal axons. J Neurophysiol 97: 3460 -3472.
Meza RC, López-Jury L, Canavier CC, Henny P (2018) Role of the axon initial segment in the control of spontaneous frequency of nigral dopaminergic neurons in vivo. J Neurosci 38: 733-744.
Migliore M, Cannia C, Canavier CC (2008) A modeling study suggesting a possible pharmacological target to mitigate the effects of ethanol on reward-related dopaminergic signaling. J Neurophysiol 99: 2703-2707.
Niven JE (2015) Neural evolution: marginal gains through soma location. Curr Biol 25: R330 -R332.
Otopalik AG, Sutton AC, Banghart M, Marder E (2017a) When complex neuronal structures may not matter. Elife 6: e23508.
Otopalik AG, Goeritz ML, Sutton AC, Brookings T, Guerini C, Marder E (2017b) Sloppy morphological tuning in identified neurons of the crustacean stomatogastric ganglion. Elife 6: e22352.
Palmer LM, Stuart GJ (2006) Site of action potential initiation in layer 5 pyramidal neurons. J Neurosci 26: 1854 -1863.
Platkiewicz J, Brette R (2010) A threshold equation for action potential initiation. PLoS Comput Biol 6: e1000850.
Prensa L, Parent A (2001) The nigrostriatal pathway in the rat: a single-axon study of the relationship between dorsal and ventral tier nigral neurons and the striosome/matrix striatal compartments. J Neurosci 21: 7247-7260.
Puopolo M, Raviola E, Bean BP (2007) Roles of subthreshold calcium current and sodium current in spontaneous firing of mouse midbrain dopamine neurons. J Neurosci 27: 645-656.
Putzier I, Kullmann PH, Horn JP, Levitan ES (2009) Dopamine neuron responses depend exponentially on pacemaker interval. J Neurophysiol 101: 926 -933.
RasbandMN (2010) The axon initial segment and the maintenance of neuronal polarity. Nat Rev Neurosci 11: 552-562.
Rueden CT, Schindelin J, Hiner MC, DeZonia BE, Walter AE, Arena ET, Eliceiri KW (2017) ImageJ2: ImageJ for the next generation of scientific image data. BMC Bioinformatics 18: 529.
Sakmann B, Neher E (1995) Single channel recordings. New York: Plenum.
Schild JH, Khushalani S, Clark JW, Andresen MC, Kunze DL, YangM (1993) An ionic current model for neurons in the rat medial nucleus tractus solitarii receiving sensory afferent input. J Physiol 469: 341-363.
Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid B, Tinevez JY, White DJ, Hartenstein V, Eliceiri K, Tomancak P, Cardona A (2012) Fiji: an opensource platform for biological-image analysis. Nat Methods 9: 676-682.
Schneider CA, Rasband WS, Eliceiri KW (2012) NIH image to ImageJ: 25 years of image analysis. Nat Methods 9: 671-675.
Scott RS, Henneberger C, Padmashri R, Anders S, Jensen TP, Rusakov DA (2014) Neuronal adaptation involves rapid expansion of the action potential initiation site. Nat Commun 5: 3817.
Seutin V, EngelD (2010) Differences in Na+ conductance density and Na+ channel functional properties between dopamine and GABA neurons of the rat substantia nigra. J Neurophysiol 103: 3099 -3114.
Tepper JM, Damlama M, Trent F (1994) Postnatal changes in the distribution and morphology of rat substantia nigra dopaminergic neurons. Neuroscience 60: 469-477.
Thome C, Kelly T, Yanez A, Schultz C, Engelhardt M, Cambridge SB, Both M, Draguhn A, Beck H, Egorov AV (2014) Axon-carrying dendrites convey privileged synaptic input in hippocampal neurons. Neuron 83: 1418-1430.
Tucker KR, Huertas MA, Horn JP, Canavier CC, Levitan ES (2012) Pacemaker rate and depolarization block in nigral dopamine neurons: a somatic sodium channel balancing act. J Neurosci 32: 14519 -14531.
van Ooyen A, Duijnhouwer J, Remme MW, van Pelt J (2002) The effect of dendritic topology on firing patterns in model neurons. Network 13: 311-325.
Van Wart A, Trimmer JS, Matthews G (2007) Polarized distribution of ion channels within microdomains of the axon initial segment. J Comp Neurol 500: 339 -352.
Vandecasteele M, Glowinski J, Deniau JM, Venance L (2008) Chemical transmission between dopaminergic neuron pairs. Proc Natl Acad Sci U S A 105: 4904-4909.
Vetter P, Roth A, Häusser M (2001) Propagation of action potentials in dendrites depends on dendritic morphology. J Neurophysiol 85: 926 -937.
Washio H, Takigachi-Hayashi K, Konishi S (1999) Early postnatal development of substantia nigra neurons in rat midbrain slices: hyperpolarization-activated inward current and dopamine-activated current. Neurosci Res 34: 91-101.
Weaver CM, Wearne SL (2008) Neuronal firing sensitivity to morphologic and active membrane parameters. PLoS Comput Biol 4: e11.
Wefelmeyer W, Cattaert D, Burrone J (2015) Activity-dependent mismatch between axo-axonic synapses and the axon initial segment controls neuronal output. Proc Natl Acad Sci U S A 112: 9757-9762.
Wilson CJ, Callaway JC (2000) Coupled oscillator model of the dopaminergic neuron of the substantia nigra. J Neurophysiol 83: 3084 -3100.
Yee AG, Forbes B, Cheung PY, Martini A, Burrell MH, Freestone PS, Lipski J (2019) Action potential and calcium dependence of tonic somatodendritic dopamine release in the Substantia Nigra pars compacta. J Neurochem 148: 462-479.
Zhou D, Lambert S, Malen PL, Carpenter S, Boland LM, Bennett V (1998) AnkyrinG is required for clustering of voltage-gated Na channels at axon initial segments and for normal action potential firing. J Cell Biol 143: 1295-1304.