Journal Article

Membrane Properties of Striatal Direct and Indirect Pathway Neurons in Mouse and Rat Slices and Their Modulation by Dopamine

Silberberg, Gilad, Planert, Henrike, Berger, Thomas K.

2013

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animal models / Animals / Artificial chromosomes / Benzazepines - pharmacology / Biology / Brain slice preparation / Cell Membrane - drug effects / Cell Membrane - metabolism / Corpus Striatum - cytology / Corpus Striatum - drug effects / Corpus Striatum - metabolism / Dopamine / Dopamine - metabolism / Dopamine - pharmacology / Dopamine Agonists - pharmacology / Dopamine D1 receptors / Dopamine D2 Receptor Antagonists / Dopamine D2 receptors / Dopamine receptors / Electrical properties / Evoked potentials / Excitability / Excitation / Excitatory Postsynaptic Potentials - drug effects / Excitatory Postsynaptic Potentials - physiology / Gene expression / Genetic aspects / Glutamatergic transmission / Green Fluorescent Proteins / Labeling / Male / Medicine / Mice / Microtomy / Modulation / Morphology / Motor task performance / Neostriatum / Neuroanatomical Tract-Tracing Techniques / Neurons / Neurons - cytology / Neurons - drug effects / Neurons - metabolism / Neurosciences / Patch-Clamp Techniques / Physiological aspects / Rats / Receptors / Receptors, Dopamine D1 - agonists / Receptors, Dopamine D1 - antagonists & inhibitors / Receptors, Dopamine D1 - metabolism / Receptors, Dopamine D2 - agonists / Receptors, Dopamine D2 - metabolism / Rodents / Sensory neurons / Spiny neurons / Studies / Synapses - drug effects / Synapses - physiology / Synaptic transmission / Transgenic animals / Transgenic mice