Dopamine Modulation of GABA Tonic Conductance in Striatal Output Neurons

Janssen, Megan J.; Ade, Kristen K.; Fu, Zhanyan; Vicini, Stefano

doi:10.1523/jneurosci.4737-08.2009

Cited by 69 publications

(104 citation statements)

References 45 publications

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“…Vicini's (Ade et al 2008;Janssen et al 2009;Janssen et al 2011;Luo et al 2013) and other groups (Kirmse et al 2008;Janssen et al 2009;Santhakumar et al 2010) have provided solid evidence for the presence and the developmental profile of a tonic GABA A current in MSNs. (Note, however, that one study did not find any evidence for a tonic GABA A current in D2 + or D1 + MSNs; Gertler et al 2008.)…”

Section: Striatummentioning

confidence: 98%

“…This is based on the evidence of (i) a differential expression α5-and β3-containing receptors in D2+ neurons compared to D1+ neurons, (ii) the similar expression and effect of δ-subunit-containing GABA A between the two MSN populations, with a minimal contribution to tonic GABA currents and (iii) the lack of effect of α1-containing GABA A R receptors activation on both D2+ and D1+ MSNs (Ade et al 2008;Janssen et al 2009;Santhakumar et al 2010;Janssen et al 2011).…”

Section: Striatummentioning

confidence: 99%

See 1 more Smart Citation

GPCR Modulation of Extrasynapitic GABAA Receptors

Connelly

Errington

Yagüe

et al. 2014

Extrasynaptic GABAA Receptors

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γ-Aminobutyric acid type A (GABA A ) receptors (GABA A Rs), the main inhibitory neurotransmitter-gated ion channels in the central nervous system, are finely tuned by other neurotransmitters and endogenous ligands. The regulation of synaptic GABA A Rs (sGABA A Rs) by G protein-coupled receptors (GPCRs) has been well characterized and is known to occur either through the conventional activation of second-messenger signalling cascades by G proteins or directly by protein-protein coupling. In contrast, research on the modulation of extrasynaptic GABA A R (eGABA A Rs) is still in its infancy and it remains to be determined whether both of the above mechanisms are capable of controlling eGABA A R function. In this chapter, we summarize the available literature on eGABA A R modulation by GPCRs, including GABA B , serotonin (5-HT), dopamine (DA), noradrenaline (NA) and metabotropic glutamate (mGlu) receptors. Although at present these GPCRs-eGABA A Rs cross-talks have been investigated in a limited number of brain areas (i.e., thalamus, cerebellum, hippocampus, striatum), it is already evident that eGABA A Rs show a nucleus-and neuronal type-selective regulation by GPCRs that differs from that of sGABA A Rs. This distinct regulation of eGABA A Rs versus sGABA A Rs by GPCRs provides mechanisms for receptor adaptation in response

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Section: Striatummentioning

confidence: 98%

Section: Striatummentioning

confidence: 99%

GPCR Modulation of Extrasynapitic GABAA Receptors

Connelly

Errington

Yagüe

et al. 2014

Extrasynaptic GABAA Receptors

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show abstract

“…The development of BAC transgenic mice in which EGFP reports the expression of dopamine D 1 or D 2 receptors and hence direct or indirect pathway MSNs has been critical in the elucidation of the properties of these subpopulations of MSNs (Gong et al, 2003;Lobo et al, 2006;Kreitzer and Malenka, 2007;Surmeier et al, 2007;Ade et al, 2008;Cepeda et al, 2008;Day et al, 2008;Gertler et al, 2008;Shen et al, 2008;Shuen et al, 2008;Janssen et al, 2009). This development, together with the discovery that VGluT1 and VGluT2 selectively label corticostriatal and thalamostriatal afferents (Fremeau et al, 2004), enabled us to directly assess and quantify the relationship between excitatory afferents and the principal neurons of the striatum.…”

Section: Cortical and Thalamic Input To Direct And Indirect Pathway Msnsmentioning

confidence: 99%

Cortical and Thalamic Innervation of Direct and Indirect Pathway Medium-Sized Spiny Neurons in Mouse Striatum

Doig¹,

Moss²,

Bolam³

2010

J. Neurosci.

203

173

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The striatum receives major excitatory inputs from the cortex and thalamus that predominantly target the spines of medium-sized spiny neurons (MSNs). We aimed to determine whether there is any selectivity of these two excitatory afferents in their innervation of direct and indirect pathway MSNs. To address this, we used bacterial artificial chromosome transgenic mice, in which enhanced green fluorescent protein (EGFP) reports the presence of D 1 or D 2 dopamine receptor subtypes, markers of direct and indirect pathway MSNs, respectively. Excitatory afferents were identified by the selective expression of vesicular glutamate transporter type 1 (VGluT1) by corticostriatal afferents and vesicular glutamate transporter type 2 (VGluT2) by thalamostriatal afferents. A quantitative electron microscopic analysis was performed on striatal tissue from D 1 and D 2 mice that was double immunolabeled to reveal the EGFP and VGluT1 or VGluT2. We found that the proportion of synapses formed by terminals derived from the cortex and thalamus was similar for both direct and indirect pathway MSNs. Furthermore, qualitative analysis revealed that individual cortical or thalamic terminals form synapses with both direct and indirect pathway MSNs. Similarly, we observed a convergence of cortical and thalamic inputs onto individual MSNs of both direct and indirect pathway: individual EGFP-positive structures received input from both VGluT2-positive and VGluT2-negative terminals. These findings demonstrate that direct and indirect pathway MSNs are similarly innervated by cortical and thalamic afferents; both projections are thus likely to be critical in the control of MSNs and hence play fundamental roles in the expression of basal ganglia function.

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“…Tonic inhibition serves to regulate the excitability of individual neurons and can alter both threshold and gain in response to excitatory inputs (4,5). GABAergic tonic inhibition in the brain has been well documented and is mediated by a distinct class of GABA A receptors (GABA A Rs) in regions such as the striatum (6)(7)(8), hippocampus (9,10), thalamus (11,12), and cerebellum (13).…”

mentioning

confidence: 99%

Glycine receptor α3 and α2 subunits mediate tonic and exogenous agonist-induced currents in forebrain

McCracken

Lowes

Salling

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Neuronal inhibition can occur via synaptic mechanisms or through tonic activation of extrasynaptic receptors. In spinal cord, glycine mediates synaptic inhibition through the activation of heteromeric glycine receptors (GlyRs) composed primarily of α1 and β subunits. Inhibitory GlyRs are also found throughout the brain, where GlyR α2 and α3 subunit expression exceeds that of α1, particularly in forebrain structures, and coassembly of these α subunits with the β subunit appears to occur to a lesser extent than in spinal cord. Here, we analyzed GlyR currents in several regions of the adolescent mouse forebrain (striatum, prefrontal cortex, hippocampus, amygdala, and bed nucleus of the stria terminalis). Our results show ubiquitous expression of GlyRs that mediate large-amplitude currents in response to exogenously applied glycine in these forebrain structures. Additionally, tonic inward currents were also detected, but only in the striatum, hippocampus, and prefrontal cortex (PFC). These tonic currents were sensitive to both strychnine and picrotoxin, indicating that they are mediated by extrasynaptic homomeric GlyRs. Recordings from mice deficient in the GlyR α3 subunit (Glra3 −/− ) revealed a lack of tonic GlyR currents in the striatum and the PFC. In Glra2 −/Y animals, GlyR tonic currents were preserved; however, the amplitudes of current responses to exogenous glycine were significantly reduced. We conclude that functional α2 and α3 GlyRs are present in various regions of the forebrain and that α3 GlyRs specifically participate in tonic inhibition in the striatum and PFC. Our findings suggest roles for glycine in regulating neuronal excitability in the forebrain.glycine receptor | tonic inhibition | Cys-loop receptor | strychnine | alpha subunits

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Dopamine Modulation of GABA Tonic Conductance in Striatal Output Neurons

Cited by 69 publications

References 45 publications

GPCR Modulation of Extrasynapitic GABAA Receptors

GPCR Modulation of Extrasynapitic GABAA Receptors

Cortical and Thalamic Innervation of Direct and Indirect Pathway Medium-Sized Spiny Neurons in Mouse Striatum

Glycine receptor α3 and α2 subunits mediate tonic and exogenous agonist-induced currents in forebrain

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