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

PLoS One. 2013;8(3):e57054. doi: 10.1371/journal.pone.0057054. Epub 2013 Mar 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzazepines / pharmacology
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism*
  • Corpus Striatum / cytology
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism*
  • Dopamine / pharmacology
  • Dopamine Agonists / pharmacology
  • Dopamine D2 Receptor Antagonists
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • Green Fluorescent Proteins
  • Male
  • Mice
  • Microtomy
  • Neuroanatomical Tract-Tracing Techniques
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Patch-Clamp Techniques
  • Rats
  • Receptors, Dopamine D1 / agonists
  • Receptors, Dopamine D1 / antagonists & inhibitors
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / agonists
  • Receptors, Dopamine D2 / metabolism
  • Synapses / drug effects
  • Synapses / physiology*


  • Benzazepines
  • Dopamine Agonists
  • Dopamine D2 Receptor Antagonists
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • SK&F 81297
  • Dopamine

Grants and funding

This work was supported by the European Commission Coordination Action ENINET (contract number LSHM-CT-2005-19063), the Human Frontier Science Program (HFSP), the Swedish Science Research Council (VRM), Jeanssons Stiftelse, the EU Marie Curie Actions (CORTEX, project No 19729), and EU FP7 (Select and Act). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.