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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

Differences between striatonigral and pallidonigral inhibitory postsynaptic currents. (A) Striatonigral inhibitory postsynaptic currents (IPSCs) exhibited paired-pulse facilitation. (B) Pallidonigral IPSCs exhibit paired-pulse depression. (C) Short-term synaptic plasticity (STP) from striatonigral afferents is facilitation. (D) STP from pallidonigral afferents is depression with numerous failures. (E) Intensity–amplitude plots (I–A plots) from striatonigral IPSCs exhibit a sigmoidal shape. (F) I–A plots from pallidonigral IPSCs exhibit a jump to maximal amplitude after reaching threshold. I–A plots were fitted to: A(I) = Amax/(1 + e−k(I−Ih)) where A(I) = IPSC amplitude as a function of stimulus intensity, Amax = maximal amplitude reached, k = slope factor, and Ih = stimulus intensity necessary to reach IPSC amplitude equal to half maximal amplitude. All parameters were significantly different. (G) Cluster plot showing that IPSCs from these sources can be separated. PPR = paired-pulse ratio. τD = decay time constant of IPSCs. RS = rise time of IPSCs.
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Figure 1: Differences between striatonigral and pallidonigral inhibitory postsynaptic currents. (A) Striatonigral inhibitory postsynaptic currents (IPSCs) exhibited paired-pulse facilitation. (B) Pallidonigral IPSCs exhibit paired-pulse depression. (C) Short-term synaptic plasticity (STP) from striatonigral afferents is facilitation. (D) STP from pallidonigral afferents is depression with numerous failures. (E) Intensity–amplitude plots (I–A plots) from striatonigral IPSCs exhibit a sigmoidal shape. (F) I–A plots from pallidonigral IPSCs exhibit a jump to maximal amplitude after reaching threshold. I–A plots were fitted to: A(I) = Amax/(1 + e−k(I−Ih)) where A(I) = IPSC amplitude as a function of stimulus intensity, Amax = maximal amplitude reached, k = slope factor, and Ih = stimulus intensity necessary to reach IPSC amplitude equal to half maximal amplitude. All parameters were significantly different. (G) Cluster plot showing that IPSCs from these sources can be separated. PPR = paired-pulse ratio. τD = decay time constant of IPSCs. RS = rise time of IPSCs.

Mentions: Procedures were carried out in accordance with the National Institutes of Health Guide for Care and Use of Laboratory Animals (NIH Publications No. 8023, revised 1996) and were approved by the Institutional Animal Care Committee of UNAM. Methods have been reported elsewhere (Beurrier et al., 2006; Ibáñez-Sandoval et al., 2006). Briefly, Wistar rats (15–40 postnatal day), were anesthetized with isoflurane, decapitated, and their brains removed. Parasagittal or parahorizontal slices (300 μm) containing the neostriatum (NSt), globus pallidus (GP), and substantia nigra pars reticulata (SNr) were obtained with a vibratome in saline of the following composition (in millimolar): 124 choline chloride, 2.5 KCl, 1.0 MgCl2, 1.2 NaH2PO4, 2.0 CaCl2, and 10 glucose (~4°C 95% O2, 5% CO2). Whole-cell patch-clamp recordings were performed on rat SNr neurons (Ibáñez-Sandoval et al., 2006, 2007). Neurons within the SNr were visualized with infrared differential interference videomicroscopy using a X60 water–immersion objective. For voltage-clamp recordings micropipettes 2–5 MΩ resistance were filled with internal saline containing high Cl− (in millimolar): 70 KH2PO4, 36 KCl, 2 MgCl2, 10 HEPES, 1.1 EGTA, 0.2 Na2ATP, 0.2 Na3GTP, 5 mM QX-314, 5 mM CsCl, and 0.1% biocytin (pH 7.2; 275 mOsM/l) that allowed to record inward IPSCs from SNr neurons after field stimulation in the internal capsule (IC) 0.5–1.0 mm outside the SNr border (Radnikow and Misgeld, 1998; Wallmichrath and Szabo, 2002). Bipolar pencil shaped concentric tungsten electrodes, 11.5 μm at the tip, and 1 kΩ DC resistance were used. For current-clamp recordings we used internal saline of the following composition (in millimolar): 120 KSO3CH4, 10 NaCl, 10 EGTA, 10 HEPES, 1 CaCl2, 2 MgCl2, 2 ATP-Mg, 0.3 GTP-Na (pH 7.3, 290 mOsM/l. Superfusion saline contained antagonists for glutamatergic receptors: 10 μM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 50 μM D-(−)-2-amino-5-phosphopentanoic acid (APV) to isolate IPSCs. In parasagittal slices, 3 out of 10 recordings evoked pallidonigral IPSCs and the rest evoked striatonigral IPSCs (Figure 1). In parahorizontal slices 6 out of 10 recordings evoked pallidonigral IPSCs and the rest evoked striatonigral IPSCs. IPSCs from each source were easily discernible with electrophysiological techniques (Figure 1; Connelly et al., 2010) so that when an obvious mixture of IPSCs from both sources was obtained, it was discarded from the present analysis. Holding potential was −80 mV. A paired-pulse protocol was employed with inter-pulse intervals of 50 ms to evaluate changes in the paired-pulse ratio (PPR) of evoked IPSCs (PPR = 2nd IPSC/1st IPSC) to verify presynaptic actions of transmitters (Ibáñez-Sandoval et al., 2006). Amplitude of first IPSC was used to build time courses of dopaminergic actions. Because striatonigral fibers pass through the GPe, D2-class selective agonists were tested in slices taken from animals with a stereotaxic lesion (ibotenic acid) of the GPe (1.4 mm AP, 3.4 L, and 4.7 mm V) and compared to recordings obtained without a lesion. The lesion further confirmed the differences of IPSCs from both sources. Ibotenic acid solution (dissolved in PBS adjusted to pH 7.4 with NaOH 3.0 μg/0.4 μl) was used to lesion the GPe. These values closely followed Paxinos and Watson (1982) coordinates system.


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)

Differences between striatonigral and pallidonigral inhibitory postsynaptic currents. (A) Striatonigral inhibitory postsynaptic currents (IPSCs) exhibited paired-pulse facilitation. (B) Pallidonigral IPSCs exhibit paired-pulse depression. (C) Short-term synaptic plasticity (STP) from striatonigral afferents is facilitation. (D) STP from pallidonigral afferents is depression with numerous failures. (E) Intensity–amplitude plots (I–A plots) from striatonigral IPSCs exhibit a sigmoidal shape. (F) I–A plots from pallidonigral IPSCs exhibit a jump to maximal amplitude after reaching threshold. I–A plots were fitted to: A(I) = Amax/(1 + e−k(I−Ih)) where A(I) = IPSC amplitude as a function of stimulus intensity, Amax = maximal amplitude reached, k = slope factor, and Ih = stimulus intensity necessary to reach IPSC amplitude equal to half maximal amplitude. All parameters were significantly different. (G) Cluster plot showing that IPSCs from these sources can be separated. PPR = paired-pulse ratio. τD = decay time constant of IPSCs. RS = rise time of IPSCs.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Differences between striatonigral and pallidonigral inhibitory postsynaptic currents. (A) Striatonigral inhibitory postsynaptic currents (IPSCs) exhibited paired-pulse facilitation. (B) Pallidonigral IPSCs exhibit paired-pulse depression. (C) Short-term synaptic plasticity (STP) from striatonigral afferents is facilitation. (D) STP from pallidonigral afferents is depression with numerous failures. (E) Intensity–amplitude plots (I–A plots) from striatonigral IPSCs exhibit a sigmoidal shape. (F) I–A plots from pallidonigral IPSCs exhibit a jump to maximal amplitude after reaching threshold. I–A plots were fitted to: A(I) = Amax/(1 + e−k(I−Ih)) where A(I) = IPSC amplitude as a function of stimulus intensity, Amax = maximal amplitude reached, k = slope factor, and Ih = stimulus intensity necessary to reach IPSC amplitude equal to half maximal amplitude. All parameters were significantly different. (G) Cluster plot showing that IPSCs from these sources can be separated. PPR = paired-pulse ratio. τD = decay time constant of IPSCs. RS = rise time of IPSCs.
Mentions: Procedures were carried out in accordance with the National Institutes of Health Guide for Care and Use of Laboratory Animals (NIH Publications No. 8023, revised 1996) and were approved by the Institutional Animal Care Committee of UNAM. Methods have been reported elsewhere (Beurrier et al., 2006; Ibáñez-Sandoval et al., 2006). Briefly, Wistar rats (15–40 postnatal day), were anesthetized with isoflurane, decapitated, and their brains removed. Parasagittal or parahorizontal slices (300 μm) containing the neostriatum (NSt), globus pallidus (GP), and substantia nigra pars reticulata (SNr) were obtained with a vibratome in saline of the following composition (in millimolar): 124 choline chloride, 2.5 KCl, 1.0 MgCl2, 1.2 NaH2PO4, 2.0 CaCl2, and 10 glucose (~4°C 95% O2, 5% CO2). Whole-cell patch-clamp recordings were performed on rat SNr neurons (Ibáñez-Sandoval et al., 2006, 2007). Neurons within the SNr were visualized with infrared differential interference videomicroscopy using a X60 water–immersion objective. For voltage-clamp recordings micropipettes 2–5 MΩ resistance were filled with internal saline containing high Cl− (in millimolar): 70 KH2PO4, 36 KCl, 2 MgCl2, 10 HEPES, 1.1 EGTA, 0.2 Na2ATP, 0.2 Na3GTP, 5 mM QX-314, 5 mM CsCl, and 0.1% biocytin (pH 7.2; 275 mOsM/l) that allowed to record inward IPSCs from SNr neurons after field stimulation in the internal capsule (IC) 0.5–1.0 mm outside the SNr border (Radnikow and Misgeld, 1998; Wallmichrath and Szabo, 2002). Bipolar pencil shaped concentric tungsten electrodes, 11.5 μm at the tip, and 1 kΩ DC resistance were used. For current-clamp recordings we used internal saline of the following composition (in millimolar): 120 KSO3CH4, 10 NaCl, 10 EGTA, 10 HEPES, 1 CaCl2, 2 MgCl2, 2 ATP-Mg, 0.3 GTP-Na (pH 7.3, 290 mOsM/l. Superfusion saline contained antagonists for glutamatergic receptors: 10 μM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 50 μM D-(−)-2-amino-5-phosphopentanoic acid (APV) to isolate IPSCs. In parasagittal slices, 3 out of 10 recordings evoked pallidonigral IPSCs and the rest evoked striatonigral IPSCs (Figure 1). In parahorizontal slices 6 out of 10 recordings evoked pallidonigral IPSCs and the rest evoked striatonigral IPSCs. IPSCs from each source were easily discernible with electrophysiological techniques (Figure 1; Connelly et al., 2010) so that when an obvious mixture of IPSCs from both sources was obtained, it was discarded from the present analysis. Holding potential was −80 mV. A paired-pulse protocol was employed with inter-pulse intervals of 50 ms to evaluate changes in the paired-pulse ratio (PPR) of evoked IPSCs (PPR = 2nd IPSC/1st IPSC) to verify presynaptic actions of transmitters (Ibáñez-Sandoval et al., 2006). Amplitude of first IPSC was used to build time courses of dopaminergic actions. Because striatonigral fibers pass through the GPe, D2-class selective agonists were tested in slices taken from animals with a stereotaxic lesion (ibotenic acid) of the GPe (1.4 mm AP, 3.4 L, and 4.7 mm V) and compared to recordings obtained without a lesion. The lesion further confirmed the differences of IPSCs from both sources. Ibotenic acid solution (dissolved in PBS adjusted to pH 7.4 with NaOH 3.0 μg/0.4 μl) was used to lesion the GPe. These values closely followed Paxinos and Watson (1982) coordinates system.

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