Abstract
Suprathreshold corticostriatal responses recorded from medium spiny neurons (MSNs) from the direct and indirect pathways of the basal ganglia are different. Their differences readily distinguish D1- and D2-type receptor expressing MSNs in both bacterial artificial chromosome-transgenic mice and their control littermates as well as in rats: indirect pathway neurons are more excitable than direct pathway neurons revealing autoregenerative spikes underlying their spike trains, whereas direct pathway neurons exhibit more prolonged plateau potentials and spike trains. SFK 81297, a selective agonist for D1-class receptors enhanced corticostriatal responses in direct pathway neurons, while quinelorane, a selective agonist for D2-class receptors reduced orthodromic and autoregenerative responses in indirect pathway neurons thus making both neuron classes similarly excitable. Because dopaminergic postsynaptic actions target CaV1 (L) class voltage-gated calcium channels in MSNs, we hypothesized that these channels are involved and can explain a part of the dopaminergic actions on corticostriatal integration. Both 2.5 μM nicardipine and 400 nM calciseptine, selective CaV1 channel blockers, reduced corticostriatal responses in both D1- and D2-receptor expressing neurons, respectively. A previous blockade of CaV1 channels occluded the actions of dopamine agonists in both neuronal classes. In contrast, a CaV1 (L) channel activator, 2.5 μM Bay K 8644, enhanced corticostriatal responses in neurons from both pathways. It is concluded that CaV1 intrinsic currents mediate a part of the dopaminergic modulation during orthodromic synaptic integration of cortical inputs in both classes of MSNs.
Highlights
Striatal dopamine (DA) is involved in initiation of learned procedures (Schultz, 2007)
Corticostriatal responses in D1-receptor expressing medium spiny neurons (MSNs) (D1-MSN) show action potentials of increasing amplitude and a slowly decaying plateau potentials, whereas D2-receptor expressing MSN (D2-MSN) shows a larger but briefer depolarization with firing of inactivating action potentials followed by a quasi exponential decay
The present work demonstrated: (1) A selective dopaminergic D1-class receptor mediated increase in firing and depolarization of the corticostriatal response in D1-MSNs in such a way as to approach the level of excitability found in D2-MSNs. (2) A selective dopaminergic D2-class receptor mediated a significant decrease in firing and depolarization of the corticostriatal response in D2-MSNs. (3) CaV1 (L) calcium currents contribute to corticostriatal integration in both D1- and D2-MSNs; including the autoregenerative response underlying the train of spikes characteristic of D2-MSNs. (4) Blockade of CaV1 channels occluded the actions of selective DA receptor agonists in their respective responsive neurons from the direct and indirect pathways
Summary
Striatal dopamine (DA) is involved in initiation of learned procedures (Schultz, 2007). Localization of different DA receptors in medium spiny neurons (MSNs) belonging to direct and indirect pathways of the basal ganglia (Gerfen, 2000) has led to the idea that balanced activity in these two pathways is regulated by opposite actions of DA in each of them: the “two pathways hypothesis” (Albin et al, 1989; Mink, 2003; Redgrave et al, 2010) Both voltage- and current-clamp data in single cells have partially confirmed these assumptions: D1-class receptor (D1R) activation facilitates firing in MSNs of the direct pathway by enhancing CaV1 (L) calcium current, whereas D2-class receptor (D2R) activation represses firing in MSNs of the indirect pathway by decreasing the same current (Surmeier et al, 1995; Hernández-López et al, 1997, 2000). We used selective agonists and antagonists of D1- and D2-class receptors, bacterial artificial chromosome (BAC) transgenic mice to identify the recorded neurons, and Frontiers in Systems Neuroscience www.frontiersin.org
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