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Dopaminergic presynaptic modulation of nigral afferents: its role in the generation of recurrent bursting in substantia nigra pars reticulata neurons.

de Jesús Aceves J, Rueda-Orozco PE, Hernández R, Plata V, Ibañez-Sandoval O, Galarraga E, Bargas J - Front Syst Neurosci (2011)

Bottom Line: No action of D(1)-class agonists was found on pallidonigral synapses.The result was that most SNr projection neurons entered a recurrent bursting firing mode similar to that observed during Parkinsonism in both patients and animal models.These results raise the question as to whether the lack of dopamine in basal ganglia output nuclei is enough to generate some pathological signs of Parkinsonism.

View Article: PubMed Central - PubMed

Affiliation: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México Distrito Federal México, México.

ABSTRACT
PREVIOUS WORK HAS SHOWN THE FUNCTIONS ASSOCIATED WITH ACTIVATION OF DOPAMINE PRESYNAPTIC RECEPTORS IN SOME SUBSTANTIA NIGRA PARS RETICULATA (SNR) AFFERENTS: (i) striatonigral terminals (direct pathway) posses presynaptic dopamine D(1)-class receptors whose action is to enhance inhibitory postsynaptic currents (IPSCs) and GABA transmission. (ii) Subthalamonigral terminals posses D(1)- and D(2)-class receptors where D(1)-class receptor activation enhances and D(2)-class receptor activation decreases excitatory postsynaptic currents. Here we report that pallidonigral afferents posses D(2)-class receptors (D(3) and D(4) types) that decrease inhibitory synaptic transmission via presynaptic modulation. No action of D(1)-class agonists was found on pallidonigral synapses. In contrast, administration of D(1)-receptor antagonists greatly decreased striatonigral IPSCs in the same preparation, suggesting that tonic dopamine levels help in maintaining the function of the striatonigral (direct) pathway. When both D(3) and D(4) type receptors were blocked, pallidonigral IPSCs increased in amplitude while striatonigral connections had no significant change, suggesting that tonic dopamine levels are repressing a powerful inhibition conveyed by pallidonigral synapses (a branch of the indirect pathway). We then blocked both D(1)- and D(2)-class receptors to acutely decrease direct pathway (striatonigral) and enhance indirect pathways (subthalamonigral and pallidonigral) synaptic force. The result was that most SNr projection neurons entered a recurrent bursting firing mode similar to that observed during Parkinsonism in both patients and animal models. These results raise the question as to whether the lack of dopamine in basal ganglia output nuclei is enough to generate some pathological signs of Parkinsonism.

No MeSH data available.


Related in: MedlinePlus

Contrasting actions of D1- and D2-receptor agonists on striatonigral and pallidonigral IPSCs. (A) 100 nM of the selective D1-class receptor agonist, SKF 81297, enhanced striatonigral IPSCs. (B) 100 nM SKF 81297, had no action on pallidonigral IPSCs. (C) 500 nM of the selective D2-class receptor agonist, quinelorane, had no significant action on striatonigral IPSCs. In some cases the GPe was lesioned to better avoid contamination from pallidonigral afferents. (D) 500 nM quinelorane greatly reduced pallidonigral IPSCs. Note changes in PPR accompanying significant effects. Record 3 in each frame is the superimposition of records 1 and 2 after normalization of the first IPSC to better appreciate the PPR change when it is present.
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Figure 2: Contrasting actions of D1- and D2-receptor agonists on striatonigral and pallidonigral IPSCs. (A) 100 nM of the selective D1-class receptor agonist, SKF 81297, enhanced striatonigral IPSCs. (B) 100 nM SKF 81297, had no action on pallidonigral IPSCs. (C) 500 nM of the selective D2-class receptor agonist, quinelorane, had no significant action on striatonigral IPSCs. In some cases the GPe was lesioned to better avoid contamination from pallidonigral afferents. (D) 500 nM quinelorane greatly reduced pallidonigral IPSCs. Note changes in PPR accompanying significant effects. Record 3 in each frame is the superimposition of records 1 and 2 after normalization of the first IPSC to better appreciate the PPR change when it is present.

Mentions: The actions of selective dopamine receptor agonists for D1- and D2-receptor classes were tested. As it has been repeatedly demonstrated, the action of dopaminergic D1-class selective agonists at nanomolar concentrations was that of enhancing striatonigral IPSCs (Floran et al., 1990; Radnikow and Misgeld, 1998; Chuhma et al., 2011): striatonigral IPSC increased 153 ± 10% after 300 nM SKF 81297 (n = 15; P < 0.001) and the paired-pulse ratio (PPR = IPSC2/IPSC1) decreased from 1.4 ± 0.13 in the control to 1.0 ± 0.12 during SKF 81297 (P < 0.001), confirming a presynaptic modulation. These actions were reversible and blocked by 100 nM of the D1-antagonist SCH 23390 (n = 5; not shown here but see below) indicating that at these concentrations the action is specific. In addition, here we show that the agonists have no significant action on pallidonigral IPSCs (cf., Figures 2A,B).


Dopaminergic presynaptic modulation of nigral afferents: its role in the generation of recurrent bursting in substantia nigra pars reticulata neurons.

de Jesús Aceves J, Rueda-Orozco PE, Hernández R, Plata V, Ibañez-Sandoval O, Galarraga E, Bargas J - Front Syst Neurosci (2011)

Contrasting actions of D1- and D2-receptor agonists on striatonigral and pallidonigral IPSCs. (A) 100 nM of the selective D1-class receptor agonist, SKF 81297, enhanced striatonigral IPSCs. (B) 100 nM SKF 81297, had no action on pallidonigral IPSCs. (C) 500 nM of the selective D2-class receptor agonist, quinelorane, had no significant action on striatonigral IPSCs. In some cases the GPe was lesioned to better avoid contamination from pallidonigral afferents. (D) 500 nM quinelorane greatly reduced pallidonigral IPSCs. Note changes in PPR accompanying significant effects. Record 3 in each frame is the superimposition of records 1 and 2 after normalization of the first IPSC to better appreciate the PPR change when it is present.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3039203&req=5

Figure 2: Contrasting actions of D1- and D2-receptor agonists on striatonigral and pallidonigral IPSCs. (A) 100 nM of the selective D1-class receptor agonist, SKF 81297, enhanced striatonigral IPSCs. (B) 100 nM SKF 81297, had no action on pallidonigral IPSCs. (C) 500 nM of the selective D2-class receptor agonist, quinelorane, had no significant action on striatonigral IPSCs. In some cases the GPe was lesioned to better avoid contamination from pallidonigral afferents. (D) 500 nM quinelorane greatly reduced pallidonigral IPSCs. Note changes in PPR accompanying significant effects. Record 3 in each frame is the superimposition of records 1 and 2 after normalization of the first IPSC to better appreciate the PPR change when it is present.
Mentions: The actions of selective dopamine receptor agonists for D1- and D2-receptor classes were tested. As it has been repeatedly demonstrated, the action of dopaminergic D1-class selective agonists at nanomolar concentrations was that of enhancing striatonigral IPSCs (Floran et al., 1990; Radnikow and Misgeld, 1998; Chuhma et al., 2011): striatonigral IPSC increased 153 ± 10% after 300 nM SKF 81297 (n = 15; P < 0.001) and the paired-pulse ratio (PPR = IPSC2/IPSC1) decreased from 1.4 ± 0.13 in the control to 1.0 ± 0.12 during SKF 81297 (P < 0.001), confirming a presynaptic modulation. These actions were reversible and blocked by 100 nM of the D1-antagonist SCH 23390 (n = 5; not shown here but see below) indicating that at these concentrations the action is specific. In addition, here we show that the agonists have no significant action on pallidonigral IPSCs (cf., Figures 2A,B).

Bottom Line: No action of D(1)-class agonists was found on pallidonigral synapses.The result was that most SNr projection neurons entered a recurrent bursting firing mode similar to that observed during Parkinsonism in both patients and animal models.These results raise the question as to whether the lack of dopamine in basal ganglia output nuclei is enough to generate some pathological signs of Parkinsonism.

View Article: PubMed Central - PubMed

Affiliation: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México Distrito Federal México, México.

ABSTRACT
PREVIOUS WORK HAS SHOWN THE FUNCTIONS ASSOCIATED WITH ACTIVATION OF DOPAMINE PRESYNAPTIC RECEPTORS IN SOME SUBSTANTIA NIGRA PARS RETICULATA (SNR) AFFERENTS: (i) striatonigral terminals (direct pathway) posses presynaptic dopamine D(1)-class receptors whose action is to enhance inhibitory postsynaptic currents (IPSCs) and GABA transmission. (ii) Subthalamonigral terminals posses D(1)- and D(2)-class receptors where D(1)-class receptor activation enhances and D(2)-class receptor activation decreases excitatory postsynaptic currents. Here we report that pallidonigral afferents posses D(2)-class receptors (D(3) and D(4) types) that decrease inhibitory synaptic transmission via presynaptic modulation. No action of D(1)-class agonists was found on pallidonigral synapses. In contrast, administration of D(1)-receptor antagonists greatly decreased striatonigral IPSCs in the same preparation, suggesting that tonic dopamine levels help in maintaining the function of the striatonigral (direct) pathway. When both D(3) and D(4) type receptors were blocked, pallidonigral IPSCs increased in amplitude while striatonigral connections had no significant change, suggesting that tonic dopamine levels are repressing a powerful inhibition conveyed by pallidonigral synapses (a branch of the indirect pathway). We then blocked both D(1)- and D(2)-class receptors to acutely decrease direct pathway (striatonigral) and enhance indirect pathways (subthalamonigral and pallidonigral) synaptic force. The result was that most SNr projection neurons entered a recurrent bursting firing mode similar to that observed during Parkinsonism in both patients and animal models. These results raise the question as to whether the lack of dopamine in basal ganglia output nuclei is enough to generate some pathological signs of Parkinsonism.

No MeSH data available.


Related in: MedlinePlus