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Regional and cell-type-specific effects of DAMGO on striatal D1 and D2 dopamine receptor-expressing medium-sized spiny neurons.

Ma YY, Cepeda C, Chatta P, Franklin L, Evans CJ, Levine MS - ASN Neuro (2012)

Bottom Line: MSSNs in the DLS were larger, had higher membrane capacitances and lower Rin (input resistances) compared with cells in the VMS.Acute application of DAMGO reduced the frequency of spontaneous excitatory and inhibitory postsynaptic currents, but the effect was greater in the VMS, in particular in the NAcS, where excitatory currents from D2 cells and inhibitory currents from D1 cells were inhibited by the largest amount.Together the present findings help elucidate the regional and cell-type-specific substrate of opioid actions in the striatum and point to the VMS as a critical mediator of DAMGO effects.

View Article: PubMed Central - PubMed

Affiliation: Stefan Shirley Hatos Center for Neuropharmacology, David Geffen School of Medicine, University of California Los Angeles, USA.

ABSTRACT
The striatum can be divided into the DLS (dorsolateral striatum) and the VMS (ventromedial striatum), which includes NAcC (nucleus accumbens core) and NAcS (nucleus accumbens shell). Here, we examined differences in electrophysiological properties of MSSNs (medium-sized spiny neurons) based on their location, expression of DA (dopamine) D1/D2 receptors and responses to the μ-opioid receptor agonist, DAMGO {[D-Ala(2)-MePhe(4)-Gly(ol)(5)]enkephalin}. The main differences in morphological and biophysical membrane properties occurred among striatal sub-regions. MSSNs in the DLS were larger, had higher membrane capacitances and lower Rin (input resistances) compared with cells in the VMS. RMPs (resting membrane potentials) were similar among regions except for D2 cells in the NAcC, which displayed a significantly more depolarized RMP. In contrast, differences in frequency of spontaneous excitatory synaptic inputs were more prominent between cell types, with D2 cells receiving significantly more excitatory inputs than D1 cells, particularly in the VMS. Inhibitory inputs were not different between D1 and D2 cells. However, MSSNs in the VMS received more inhibitory inputs than those in the DLS. Acute application of DAMGO reduced the frequency of spontaneous excitatory and inhibitory postsynaptic currents, but the effect was greater in the VMS, in particular in the NAcS, where excitatory currents from D2 cells and inhibitory currents from D1 cells were inhibited by the largest amount. DAMGO also increased cellular excitability in the VMS, as shown by reduced threshold for evoking APs (action potentials). Together the present findings help elucidate the regional and cell-type-specific substrate of opioid actions in the striatum and point to the VMS as a critical mediator of DAMGO effects.

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Whole-cell current clamp recordings from striatal MSSNs(A) Sample traces show a gradient of inward rectification evaluated by recording responses to hyperpolarizing current steps: there is an increase from DLS to VMS (note increased voltage deflections below dashed lines in VMS compared with DLS). (B) I–V plots from groups of D1 (left panel) or D2 (right panel) receptor-expressing MSSNs, n = 9–10 in each group. The data were analysed using ANOVA with repeated measures followed by Bonferroni post hoc test. *P<0.05, ***P<0.001 respectively.
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Figure 2: Whole-cell current clamp recordings from striatal MSSNs(A) Sample traces show a gradient of inward rectification evaluated by recording responses to hyperpolarizing current steps: there is an increase from DLS to VMS (note increased voltage deflections below dashed lines in VMS compared with DLS). (B) I–V plots from groups of D1 (left panel) or D2 (right panel) receptor-expressing MSSNs, n = 9–10 in each group. The data were analysed using ANOVA with repeated measures followed by Bonferroni post hoc test. *P<0.05, ***P<0.001 respectively.

Mentions: In current clamp recordings all striatal MSSNs showed hyperpolarized RMPs. There were no significant differences in RMPs except for D2 cells in the NAcC, which were significantly more depolarized (Table 1). Inward rectification, which is caused by inwardly rectifying K+ channels, and typically observed in striatal MSSNs, was more prominent in VMS than in DLS (Figures 2A and 2B), specifically in D1 cells of the NAcS. Differences between D1 cells from NAcS and DLS were statistically significant (ANOVA repeated measures confirmed by Bonferroni post hoc tests, P<0.05). A rapid, small amplitude ‘sag’ (similar to the time- and voltage-dependent rectification induced by Ih), was rarely seen in MSSNs of DLS, but it became more prominent in MSSNs of VMS, except for D2 cells in the NAcC (Figure 2A, Table 1). Finally, the rheobase, which is the minimal current to evoke APs, showed a significant decrease from DLS to VMS. In general, D2 cells showed a lower rheobase compared with D1 cells, suggesting D2 cells, especially in the NAc, are more excitable (Table 1).


Regional and cell-type-specific effects of DAMGO on striatal D1 and D2 dopamine receptor-expressing medium-sized spiny neurons.

Ma YY, Cepeda C, Chatta P, Franklin L, Evans CJ, Levine MS - ASN Neuro (2012)

Whole-cell current clamp recordings from striatal MSSNs(A) Sample traces show a gradient of inward rectification evaluated by recording responses to hyperpolarizing current steps: there is an increase from DLS to VMS (note increased voltage deflections below dashed lines in VMS compared with DLS). (B) I–V plots from groups of D1 (left panel) or D2 (right panel) receptor-expressing MSSNs, n = 9–10 in each group. The data were analysed using ANOVA with repeated measures followed by Bonferroni post hoc test. *P<0.05, ***P<0.001 respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3297119&req=5

Figure 2: Whole-cell current clamp recordings from striatal MSSNs(A) Sample traces show a gradient of inward rectification evaluated by recording responses to hyperpolarizing current steps: there is an increase from DLS to VMS (note increased voltage deflections below dashed lines in VMS compared with DLS). (B) I–V plots from groups of D1 (left panel) or D2 (right panel) receptor-expressing MSSNs, n = 9–10 in each group. The data were analysed using ANOVA with repeated measures followed by Bonferroni post hoc test. *P<0.05, ***P<0.001 respectively.
Mentions: In current clamp recordings all striatal MSSNs showed hyperpolarized RMPs. There were no significant differences in RMPs except for D2 cells in the NAcC, which were significantly more depolarized (Table 1). Inward rectification, which is caused by inwardly rectifying K+ channels, and typically observed in striatal MSSNs, was more prominent in VMS than in DLS (Figures 2A and 2B), specifically in D1 cells of the NAcS. Differences between D1 cells from NAcS and DLS were statistically significant (ANOVA repeated measures confirmed by Bonferroni post hoc tests, P<0.05). A rapid, small amplitude ‘sag’ (similar to the time- and voltage-dependent rectification induced by Ih), was rarely seen in MSSNs of DLS, but it became more prominent in MSSNs of VMS, except for D2 cells in the NAcC (Figure 2A, Table 1). Finally, the rheobase, which is the minimal current to evoke APs, showed a significant decrease from DLS to VMS. In general, D2 cells showed a lower rheobase compared with D1 cells, suggesting D2 cells, especially in the NAc, are more excitable (Table 1).

Bottom Line: MSSNs in the DLS were larger, had higher membrane capacitances and lower Rin (input resistances) compared with cells in the VMS.Acute application of DAMGO reduced the frequency of spontaneous excitatory and inhibitory postsynaptic currents, but the effect was greater in the VMS, in particular in the NAcS, where excitatory currents from D2 cells and inhibitory currents from D1 cells were inhibited by the largest amount.Together the present findings help elucidate the regional and cell-type-specific substrate of opioid actions in the striatum and point to the VMS as a critical mediator of DAMGO effects.

View Article: PubMed Central - PubMed

Affiliation: Stefan Shirley Hatos Center for Neuropharmacology, David Geffen School of Medicine, University of California Los Angeles, USA.

ABSTRACT
The striatum can be divided into the DLS (dorsolateral striatum) and the VMS (ventromedial striatum), which includes NAcC (nucleus accumbens core) and NAcS (nucleus accumbens shell). Here, we examined differences in electrophysiological properties of MSSNs (medium-sized spiny neurons) based on their location, expression of DA (dopamine) D1/D2 receptors and responses to the μ-opioid receptor agonist, DAMGO {[D-Ala(2)-MePhe(4)-Gly(ol)(5)]enkephalin}. The main differences in morphological and biophysical membrane properties occurred among striatal sub-regions. MSSNs in the DLS were larger, had higher membrane capacitances and lower Rin (input resistances) compared with cells in the VMS. RMPs (resting membrane potentials) were similar among regions except for D2 cells in the NAcC, which displayed a significantly more depolarized RMP. In contrast, differences in frequency of spontaneous excitatory synaptic inputs were more prominent between cell types, with D2 cells receiving significantly more excitatory inputs than D1 cells, particularly in the VMS. Inhibitory inputs were not different between D1 and D2 cells. However, MSSNs in the VMS received more inhibitory inputs than those in the DLS. Acute application of DAMGO reduced the frequency of spontaneous excitatory and inhibitory postsynaptic currents, but the effect was greater in the VMS, in particular in the NAcS, where excitatory currents from D2 cells and inhibitory currents from D1 cells were inhibited by the largest amount. DAMGO also increased cellular excitability in the VMS, as shown by reduced threshold for evoking APs (action potentials). Together the present findings help elucidate the regional and cell-type-specific substrate of opioid actions in the striatum and point to the VMS as a critical mediator of DAMGO effects.

Show MeSH
Related in: MedlinePlus