Disinhibition Bursting of Dopaminergic Neurons
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2011-05-01
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| Series: | Frontiers in Systems Neuroscience |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnsys.2011.00025/full |
| _version_ | 1819229097029533696 |
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| author | Collin J Lobb Todd W Troyer Charles J Wilson Carlos A Paladini |
| author_facet | Collin J Lobb Todd W Troyer Charles J Wilson Carlos A Paladini |
| author_sort | Collin J Lobb |
| collection | DOAJ |
| description | 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 GABAA 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. |
| first_indexed | 2024-12-23T11:07:45Z |
| format | Article |
| id | doaj.art-2e7a8cb7259d45cf81940295cf80992d |
| institution | Directory Open Access Journal |
| issn | 1662-5137 |
| language | English |
| last_indexed | 2024-12-23T11:07:45Z |
| publishDate | 2011-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Systems Neuroscience |
| spelling | doaj.art-2e7a8cb7259d45cf81940295cf80992d2022-12-21T17:49:26ZengFrontiers Media S.A.Frontiers in Systems Neuroscience1662-51372011-05-01510.3389/fnsys.2011.000259800Disinhibition Bursting of Dopaminergic NeuronsCollin J Lobb0Todd W Troyer1Charles J Wilson2Carlos A Paladini3University of Texas at San AntonioUniversity of Texas at San AntonioUniversity of Texas at San AntonioUniversity of Texas at San AntonioSubstantia 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 GABAA 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.http://journal.frontiersin.org/Journal/10.3389/fnsys.2011.00025/fullDopamineGABAnetworkModelburst |
| spellingShingle | Collin J Lobb Todd W Troyer Charles J Wilson Carlos A Paladini Disinhibition Bursting of Dopaminergic Neurons Frontiers in Systems Neuroscience Dopamine GABA network Model burst |
| title | Disinhibition Bursting of Dopaminergic Neurons |
| title_full | Disinhibition Bursting of Dopaminergic Neurons |
| title_fullStr | Disinhibition Bursting of Dopaminergic Neurons |
| title_full_unstemmed | Disinhibition Bursting of Dopaminergic Neurons |
| title_short | Disinhibition Bursting of Dopaminergic Neurons |
| title_sort | disinhibition bursting of dopaminergic neurons |
| topic | Dopamine GABA network Model burst |
| url | http://journal.frontiersin.org/Journal/10.3389/fnsys.2011.00025/full |
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