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Membrane properties of striatal direct and indirect pathway neurons in mouse and rat slices and their modulation by dopamine.

Planert H, Berger TK, Silberberg G - PLoS ONE (2013)

Bottom Line: DA had opposite effects on excitability of D1 and D2 MSNs, counteracting the initial differences.Pronounced changes in AP shape were seen in D2 MSNs.In direct pathway MSNs, excitability increased across experimental conditions and parameters, and also when applying DA or the D1 agonist SKF-81297 in presence of blockers of cholinergic, GABAergic, and glutamatergic receptors.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Karolinska Institute, Stockholm, Sweden. Henrike.Planert@ki.se

ABSTRACT
D1 and D2 receptor expressing striatal medium spiny neurons (MSNs) are ascribed to striatonigral ("direct") and striatopallidal ("indirect") pathways, respectively, that are believed to function antagonistically in motor control. Glutamatergic synaptic transmission onto the two types is differentially affected by Dopamine (DA), however, less is known about the effects on MSN intrinsic electrical properties. Using patch clamp recordings, we comprehensively characterized the two pathways in rats and mice, and investigated their DA modulation. We identified the direct pathway by retrograde labeling in rats, and in mice we used transgenic animals in which EGFP is expressed in D1 MSNs. MSNs were subjected to a series of current injections to pinpoint differences between the populations, and in mice also following bath application of DA. In both animal models, most electrical properties were similar, however, membrane excitability as measured by step and ramp current injections consistently differed, with direct pathway MSNs being less excitable than their counterparts. DA had opposite effects on excitability of D1 and D2 MSNs, counteracting the initial differences. Pronounced changes in AP shape were seen in D2 MSNs. In direct pathway MSNs, excitability increased across experimental conditions and parameters, and also when applying DA or the D1 agonist SKF-81297 in presence of blockers of cholinergic, GABAergic, and glutamatergic receptors. Thus, DA induced changes in excitability were D1 R mediated and intrinsic to direct pathway MSNs, and not a secondary network effect of altered synaptic transmission. DAergic modulation of intrinsic properties therefore acts in a synergistic manner with previously reported effects of DA on afferent synaptic transmission and dendritic processing, supporting the antagonistic model for direct vs. indirect striatal pathway function.

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Direct pathway excitability increases when applying DA or D1 agonist during blockade of synaptic transmission.A, spontaneous synaptic activity is absent after addition of CNQX (10 µM), AP V (12.5 µM), SR-95531 (10 µM), Atropine (1 µM), MLA (10 nM) and Mecamylamine (10 µM) to the bath. B, example response of a D1 MSN to suprathreshold step currents before and after application of DA (dark and light gray traces, respectively), demonstrating positive modulation of discharge also in presence of blockers of synaptic transmission. C, effect of DA on excitability in n = 9 D1 MSNs when stimulating from near - 80 mV (−81.00±1.41 mV for control traces and −80.58±1.38 mV after DA application) with drugs present in the bath. Discharge increased significantly (number of APs before DA application: 3.56±0.88, after DA: 10.00±4.73, p = 0.0041, two-tailed paired t-test). D, discharge also increased after addition of SKF 81297 (1 µM) to the bath (n = 9 D1 MSNs, number of APs in control: 3.22±1.9, SKF 81297∶8.33±5.7, p = 0.01, with - 81.26±2.0 mV for control traces and - 81.10±2.2 mV after agonist application).
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pone-0057054-g006: Direct pathway excitability increases when applying DA or D1 agonist during blockade of synaptic transmission.A, spontaneous synaptic activity is absent after addition of CNQX (10 µM), AP V (12.5 µM), SR-95531 (10 µM), Atropine (1 µM), MLA (10 nM) and Mecamylamine (10 µM) to the bath. B, example response of a D1 MSN to suprathreshold step currents before and after application of DA (dark and light gray traces, respectively), demonstrating positive modulation of discharge also in presence of blockers of synaptic transmission. C, effect of DA on excitability in n = 9 D1 MSNs when stimulating from near - 80 mV (−81.00±1.41 mV for control traces and −80.58±1.38 mV after DA application) with drugs present in the bath. Discharge increased significantly (number of APs before DA application: 3.56±0.88, after DA: 10.00±4.73, p = 0.0041, two-tailed paired t-test). D, discharge also increased after addition of SKF 81297 (1 µM) to the bath (n = 9 D1 MSNs, number of APs in control: 3.22±1.9, SKF 81297∶8.33±5.7, p = 0.01, with - 81.26±2.0 mV for control traces and - 81.10±2.2 mV after agonist application).

Mentions: In order to address this question, we investigated the effect of DA on D1 MSN excitability while blocking muscarinic and nicotinergic cholinergic, as well as GABAa and glutamatergic AMPA and NMDA receptor mediated signalling (Fig. 6). Spontaneous synaptic activity was virtually absent after addition of Atropine (1 µM), MLA (10 nM) and Mec (10 µM), as well as GABAzine (10 µM), CNQX (10 µM) and AP5 (12.5 µM) to the bath (Fig. 6A), but DA still strongly increased AP discharge (p<0.01, Fig. 6B, C).


Membrane properties of striatal direct and indirect pathway neurons in mouse and rat slices and their modulation by dopamine.

Planert H, Berger TK, Silberberg G - PLoS ONE (2013)

Direct pathway excitability increases when applying DA or D1 agonist during blockade of synaptic transmission.A, spontaneous synaptic activity is absent after addition of CNQX (10 µM), AP V (12.5 µM), SR-95531 (10 µM), Atropine (1 µM), MLA (10 nM) and Mecamylamine (10 µM) to the bath. B, example response of a D1 MSN to suprathreshold step currents before and after application of DA (dark and light gray traces, respectively), demonstrating positive modulation of discharge also in presence of blockers of synaptic transmission. C, effect of DA on excitability in n = 9 D1 MSNs when stimulating from near - 80 mV (−81.00±1.41 mV for control traces and −80.58±1.38 mV after DA application) with drugs present in the bath. Discharge increased significantly (number of APs before DA application: 3.56±0.88, after DA: 10.00±4.73, p = 0.0041, two-tailed paired t-test). D, discharge also increased after addition of SKF 81297 (1 µM) to the bath (n = 9 D1 MSNs, number of APs in control: 3.22±1.9, SKF 81297∶8.33±5.7, p = 0.01, with - 81.26±2.0 mV for control traces and - 81.10±2.2 mV after agonist application).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585935&req=5

pone-0057054-g006: Direct pathway excitability increases when applying DA or D1 agonist during blockade of synaptic transmission.A, spontaneous synaptic activity is absent after addition of CNQX (10 µM), AP V (12.5 µM), SR-95531 (10 µM), Atropine (1 µM), MLA (10 nM) and Mecamylamine (10 µM) to the bath. B, example response of a D1 MSN to suprathreshold step currents before and after application of DA (dark and light gray traces, respectively), demonstrating positive modulation of discharge also in presence of blockers of synaptic transmission. C, effect of DA on excitability in n = 9 D1 MSNs when stimulating from near - 80 mV (−81.00±1.41 mV for control traces and −80.58±1.38 mV after DA application) with drugs present in the bath. Discharge increased significantly (number of APs before DA application: 3.56±0.88, after DA: 10.00±4.73, p = 0.0041, two-tailed paired t-test). D, discharge also increased after addition of SKF 81297 (1 µM) to the bath (n = 9 D1 MSNs, number of APs in control: 3.22±1.9, SKF 81297∶8.33±5.7, p = 0.01, with - 81.26±2.0 mV for control traces and - 81.10±2.2 mV after agonist application).
Mentions: In order to address this question, we investigated the effect of DA on D1 MSN excitability while blocking muscarinic and nicotinergic cholinergic, as well as GABAa and glutamatergic AMPA and NMDA receptor mediated signalling (Fig. 6). Spontaneous synaptic activity was virtually absent after addition of Atropine (1 µM), MLA (10 nM) and Mec (10 µM), as well as GABAzine (10 µM), CNQX (10 µM) and AP5 (12.5 µM) to the bath (Fig. 6A), but DA still strongly increased AP discharge (p<0.01, Fig. 6B, C).

Bottom Line: DA had opposite effects on excitability of D1 and D2 MSNs, counteracting the initial differences.Pronounced changes in AP shape were seen in D2 MSNs.In direct pathway MSNs, excitability increased across experimental conditions and parameters, and also when applying DA or the D1 agonist SKF-81297 in presence of blockers of cholinergic, GABAergic, and glutamatergic receptors.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Karolinska Institute, Stockholm, Sweden. Henrike.Planert@ki.se

ABSTRACT
D1 and D2 receptor expressing striatal medium spiny neurons (MSNs) are ascribed to striatonigral ("direct") and striatopallidal ("indirect") pathways, respectively, that are believed to function antagonistically in motor control. Glutamatergic synaptic transmission onto the two types is differentially affected by Dopamine (DA), however, less is known about the effects on MSN intrinsic electrical properties. Using patch clamp recordings, we comprehensively characterized the two pathways in rats and mice, and investigated their DA modulation. We identified the direct pathway by retrograde labeling in rats, and in mice we used transgenic animals in which EGFP is expressed in D1 MSNs. MSNs were subjected to a series of current injections to pinpoint differences between the populations, and in mice also following bath application of DA. In both animal models, most electrical properties were similar, however, membrane excitability as measured by step and ramp current injections consistently differed, with direct pathway MSNs being less excitable than their counterparts. DA had opposite effects on excitability of D1 and D2 MSNs, counteracting the initial differences. Pronounced changes in AP shape were seen in D2 MSNs. In direct pathway MSNs, excitability increased across experimental conditions and parameters, and also when applying DA or the D1 agonist SKF-81297 in presence of blockers of cholinergic, GABAergic, and glutamatergic receptors. Thus, DA induced changes in excitability were D1 R mediated and intrinsic to direct pathway MSNs, and not a secondary network effect of altered synaptic transmission. DAergic modulation of intrinsic properties therefore acts in a synergistic manner with previously reported effects of DA on afferent synaptic transmission and dendritic processing, supporting the antagonistic model for direct vs. indirect striatal pathway function.

Show MeSH
Related in: MedlinePlus