Differential electrophysiological properties of dopamine D1 and D2 receptor‐containing striatal medium‐sized spiny neurons

Abstract

The electrophysiological properties of distinct subpopulations of striatal medium-sized spiny neurons (MSSNs) were compared using enhanced green fluorescent protein as a reporter gene for identification of neurons expressing dopamine D1 and D2 receptor subtypes in mice. Whole-cell patch-clamp recordings in slices revealed that passive membrane properties were similar in D1 and D2 cells. All MSSNs displayed hyperpolarized resting membrane potentials but the threshold for firing action potentials was lower in D2 than in D1 neurons. In voltage clamp, the frequency of spontaneous excitatory postsynaptic currents was higher in D2 than in D1 cells and large-amplitude inward currents (> 100 pA) were observed only in D2 cells. After tetrodotoxin this difference was reduced, suggesting that sodium conductances contribute to the increased frequencies in D2 cells. After pharmacological blockade of GABA(A) receptors, a subset of D2 cells also displayed large spontaneous membrane depolarizations and complex responses to stimulation of the corticostriatal pathway. To further characterize ionotropic glutamate receptor function, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) was applied onto dissociated MSSNs. Application of AMPA alone or in the presence of cyclothiazide (an AMPA receptor desensitization blocker) evoked larger currents in D1 than in D2 cells. Together, these data demonstrate significant differences in electrophysiological properties of subpopulations of MSSNs defined by selective expression of D1 and D2 receptors. D2 cells display increased excitability and reflect ongoing cortical activity more faithfully than D1 cells, an effect that is independent of postsynaptic AMPA receptors and probably results from stronger synaptic coupling. This could help to explain the increased vulnerability of D2 MSSNs in neurodegenerative disorders.

Cocaine-Induced Changes of Synaptic Transmission in the Striatum are Modulated by Adenosine A2A Receptors and Involve the Tyrosine Phosphatase STEP

“…As this lack of effect could be due to a poor penetration of the peptide into the cells, we performed whole-cell voltage clamp experiments in MSNs to record excitatory synaptic transmission, and TAT-STEP (100 nM) was added to the intracellular solution of the patch pipette. In the striatum, the majority of cells (95%) are MSNs that exhibited negative resting membrane potentials and passive membrane properties similar to those previously reported (Cepeda et al, 2008). Twenty-minute slice perfusion with cocaine (10 mM) caused an inhibition of AMPA-EPSC (83.67±1.3% of basal Figure 5a and a 1 ), in accordance with the results obtained with extracellular recordings.…”

Dopamine-Dependent Long-Term Depression Is Expressed in Striatal Spiny Neurons of Both Direct and Indirect Pathways: Implications for Parkinson's Disease

“…Therefore, many researchers have adopted this method to identify and highlight the characteristics of the direct and indirect pathway neurons. Compelling evidence obtained by the use of this transgenic mouse model have demonstrated the existence of differences between striatonigral and striatopallidal MSNs, with respect to their intrinsic membrane properties and synaptic plasticity, in physiological and pathological conditions Kreitzer and Malenka, 2007;Cepeda et al, 2008;Shen et al, 2008;BertranGonzalez et al, 2009). …”

Cortical and Thalamic Innervation of Direct and Indirect Pathway Medium-Sized Spiny Neurons in Mouse Striatum

“…The development of BAC transgenic mice in which EGFP reports the expression of dopamine D 1 or D 2 receptors and hence direct or indirect pathway MSNs has been critical in the elucidation of the properties of these subpopulations of MSNs (Gong et al, 2003;Lobo et al, 2006;Kreitzer and Malenka, 2007;Surmeier et al, 2007;Ade et al, 2008;Cepeda et al, 2008;Day et al, 2008;Gertler et al, 2008;Shen et al, 2008;Shuen et al, 2008;Janssen et al, 2009). This development, together with the discovery that VGluT1 and VGluT2 selectively label corticostriatal and thalamostriatal afferents (Fremeau et al, 2004), enabled us to directly assess and quantify the relationship between excitatory afferents and the principal neurons of the striatum.…”