Modulation of AMPA currents by D1-like but not D2-like receptors in spinal motoneurons

Abstract

Dopamine can modulate and excite spinal locomotor networks, affect afferent transmission and increase motoneuronal excitability. One of the mechanisms whereby dopamine increases motoneuronal excitability is to potentiate AMPA channel-mediated glutamatergic transmission onto motoneurons. However, it is not known which dopaminergic receptor subtypes or the intracellular mechanisms contribute to these effects. In this study, we used whole-cell patch clamp techniques to record chemically evoked AMPA currents in neonatal mouse motoneurons. Bath application of D1-like receptor agonist (SKF 39383) increased the AMPA current amplitude and prolonged the decay time constant. In the presence of D1 receptor antagonist LE300, the effects of DA on AMPA currents were blocked. In contrast, bath-application of the D2-like receptor agonist quinpirole did not modulate AMPA currents. In the presence of D2 receptor antagonist L-741626, dopaminergic modulation of AMPA currents was unaffected. These results suggest that augmentation of AMPA transmission by dopamine is accomplished by D1 receptor-based mechanisms. This short-term modulation does not appear to involve cycling of AMPA receptor into the membrane, since blocking insertion with botulinum toxin C did not affect the augmentation of AMPA currents after activating D1 receptors. On the other hand, blocking protein kinase A (PKA) with H-89 completely abolished the effects of D1 agonists. In addition, we used cell-attached single channel recording to demonstrate that stimulating D1 receptors increased individual AMPA channel open probability and open duration. Our data demonstrate that dopamine increases the efficacy of glutamatergic transmission onto motoneurons by increasing AMPA conductances via a D1 PKA-based signaling system.