title: Disinhibition bursting of dopaminergic neurons.
abstract: Substantia nigra pars compacta (SNpc) dopaminergic neurons receive strong tonic inputs from GABAergic neurons in the substantia nigra pars reticulata (SNpr) and globus pallidus (GP), and glutamatergic neurons in the subthalamic nucleus. The presence of these tonic inputs raises the possibility that phasic disinhibition may trigger phasic bursts in dopaminergic neurons. We first applied constant NMDA and GABA(A) conductances onto a two-compartment single cell model of the dopaminergic neuron (Kuznetsov et al., 2006). The model exhibited disinhibition bursting upon stepwise removal of inhibition. A further bifurcation analysis suggests that disinhibition may be more robust than excitation alone in that for most levels of NMDA conductance, the cell remains capable of bursting even after a complete removal of inhibition, whereas too much excitatory input will drive the cell into depolarization block. To investigate the network dynamics of disinhibition, we used a modified version of an integrate-and-fire based model of the basal ganglia (Humphries et al., 2006). Synaptic activity generated in the network was delivered to the two-compartment single cell dopaminergic neuron. Phasic activation of the D1-expressing medium spiny neurons in the striatum (D1STR) produced disinhibition bursts in dopaminergic neurons through the direct pathway (D1STR to SNpr to SNpc). Anatomical studies have shown that D1STR neurons have collaterals that terminate in GP. Adding these collaterals to the model, we found that striatal activation increased the intra-burst firing frequency of the disinhibition burst as the weight of this connection was increased. Our studies suggest that striatal activation is a robust means by which disinhibition bursts can be generated by SNpc dopaminergic neurons, and that recruitment of the indirect pathway via collaterals may enhance disinhibition bursting.
authors: Neurosciences Institute, University of Texas at San Antonio, San Antonio, TX, USA.
authors: Collin J
authors: CJ
authors: Lobb
authors: Todd W
authors: TW
authors: Troyer
authors: Charles J
authors: CJ
authors: Wilson
authors: Carlos A
authors: CA
authors: Paladini
references: J Neurophysiol. 1998 Jul;80(1):1-27
references: 9658025
references: Synapse. 1999 Jun 1;32(3):165-76
references: 10340627
references: J Neurophysiol. 2010 Jul;104(1):403-13
references: 20445035
references: J Neurosci. 2009 Sep 2;29(35):11011-9
references: 19726659
references: Trends Neurosci. 1999 Apr;22(4):146-51
references: 10203849
references: J Neurosci. 1989 Oct;9(10):3463-81
references: 2795134
references: Nature. 2010 Jul 22;466(7305):457-62
references: 20651684
references: J Neurophysiol. 2000 May;83(5):3084-100
references: 10805703
references: J Neurophysiol. 2007 Apr;97(4):2837-50
references: 17251363
references: J Neurosci. 2010 May 26;30(21):7401-13
references: 20505107
references: Neuroscience. 1995 Jul;67(2):373-81
references: 7545793
references: J Neurosci. 2009 Dec 16;29(50):15888-97
references: 20016105
references: J Neurosci. 2006 Dec 13;26(50):12921-42
references: 17167083
references: Eur J Neurosci. 1993 Feb 1;5(2):137-44
references: 8261095
references: Neuroreport. 1994 Jun 2;5(10):1185-8
references: 7919161
references: J Neurosci. 1990 Oct;10(10):3421-38
references: 1698947
references: Prog Brain Res. 2007;160:189-208
references: 17499115
references: J Neurophysiol. 2011 May;105(5):2501-11
references: 21367999
references: J Neurosci. 2009 Dec 9;29(49):15531-41
references: 20007477
references: J Neurosci. 1984 Nov;4(11):2877-90
references: 6150071
references: Nature. 1984 Oct 4-10;311(5985):461-4
references: 6207434
references: J Neurosci. 2003 Jan 1;23(1):149-57
references: 12514211
references: Brain Res. 1985 May 6;333(2):271-84
references: 2986775
references: Acta Physiol Scand. 1986 Nov;128(3):351-8
references: 3788613
references: J Neurophysiol. 2006 Feb;95(2):932-47
references: 16207783
references: Acta Physiol Scand. 1991 May;142(1):105-12
references: 1877358
references: Synapse. 1992 Dec;12(4):287-303
references: 1465742
references: Brain Res. 1997 Jun 13;759(2):251-8
references: 9221945
references: Synapse. 1992 Feb;10(2):131-40
references: 1533955
references: Brain Res. 1995 Nov 6;698(1-2):280-4
references: 8581498
references: Science. 1997 Mar 14;275(5306):1593-9
references: 9054347
references: Brain Res. 1986 Apr 30;372(1):21-30
references: 3708356
references: J Neurosci. 2008 Oct 8;28(41):10386-98
references: 18842898