Dissociable effects of dopamine on neuronal firing rate and synchrony in the dorsal striatum

John M Burkhardt

doi:10.3389/neuro.07.028.2009

Abstract

Previous studies showed that dopamine depletion leads to both changes in firing rate and in neuronal synchrony in the basal ganglia. Since dopamine D1 and D2 receptors are preferentially expressed in striatonigral and striatopallidal medium spiny neurons, respectively, we investigated the relative contribution of lack of D1 and/or D2-type receptor activation to the changes in striatal firing rate and synchrony observed after dopamine depletion. Similar to what was observed after dopamine depletion, co-administration of D1 and D2 antagonists to mice chronically implanted with multielectrode arrays in the striatum caused significant changes in firing rate, power of the local field potential (LFP) oscillations, and synchrony measured by the entrainment of neurons to striatal local field potentials. However, although blockade of either D1 or D2 type receptors produced similarly severe akinesia, the effects on neural activity differed. Blockade of D2 receptors affected the firing rate of medium spiny neurons and the power of the LFP oscillations substantially, but it did not affect synchrony to the same extent. In contrast, D1 blockade affected synchrony dramatically, but had less substantial effects on firing rate and LFP power. Furthermore, there was no consistent relation between neurons changing firing rate and changing LFP entrainment after dopamine blockade. Our results suggest that the changes in rate and entrainment to the LFP observed in medium spiny neurons after dopamine depletion are somewhat dissociable, and that lack of D1- or D2-type receptor activation can exert independent yet interactive pathological effects during the progression of Parkinson's disease.

Highlights

The basal ganglia are known to be involved in action selection and movement initiation (Groenewegen, 2003; Gurney et al, 2004)
Since dopamine D1–type receptors (D1) and D2–type receptors (D2) receptors are preferentially expressed in striatonigral and striatopallidal medium spiny neurons, respectively, we investigated the relative contribution of lack of D1 and/or D2-type receptor activation to the changes in striatal firing rate and synchrony observed after dopamine depletion
Concurrent blockade of D1 and D2 receptors caused significant changes in striatal neural activity and synchrony, and recapitulated the effects observed after acute dopamine depletion (Costa et al, 2006)

Summary

Introduction

The basal ganglia are known to be involved in action selection and movement initiation (Groenewegen, 2003; Gurney et al, 2004). Dopamine (DA) transmission within the basal ganglia is essential for the normal expression of spontaneous and voluntary movement (Poirier et al, 1975; Amalric and Koob, 1987; Fletcher and Starr, 1987; Zhou and Palmiter, 1995). Loss of DA projections is the characteristic morphological feature of Parkinson’s disease (PD) (Shimohama et al, 2003), wherein degeneration of substantia nigra pars compacta (SNc) projections results in decreased extracellular striatal DA levels (Schober, 2004). Several recent studies failed to observe overall decrease in firing rate in motor cortex after dopamine depletion (Goldberg et al, 2004; Costa et al, 2006), even when pronounced changes in striatal firing rate were observed (Costa et al, 2006)

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