D2Dopamine Receptors in Striatal Medium Spiny Neurons Reduce L-Type Ca2+Currents and Excitability via a Novel PLCβ1–IP3–Calcineurin-Signaling Cascade

Hernández‐López, Salvador; Tkatch, Tatiana; Pérez-Garci, Enrique; Galarraga, Elvira; Bargas, José; Hamm, Heidi E.; Surmeier, D. James

doi:10.1523/jneurosci.20-24-08987.2000

Cited by 461 publications

(414 citation statements)

References 57 publications

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“…The enhancement of paired pulse facilitation, together with the lack of any postsynaptic action of these compounds on IPSC reversal potential, holding current and membrane conductance, all point to a presynaptic site for this action. Accordingly, although DA receptors are abundantly expressed postsynaptically on striatal neurons (Surmeier et al 1996), their activation is known to modulate membrane conductances operating in voltage ranges far from the values chosen in this study to evoke synaptic events (Ϫ80 mV and Ϫ40 mV) (Schiffmann et al 1995;Surmeier et al 1995;Lin et al 1996;Hernandez-Lopez et al 2000). This observation, therefore, further confirms that the postsynaptic effects of DA receptor activation cannot be responsible for the observed modulation of striatal IPSCs.…”

Section: Discussionsupporting

confidence: 78%

Cocaine and Amphetamine Depress Striatal GABAergic Synaptic Transmission through D2 Dopamine Receptors

Centonze

Picconi

Baunez

et al. 2002

Neuropsychopharmacology

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The striatum is a brain area implicated in the pharmacological action of drugs of abuse. To test the possible involvement of both cocaine and amphetamine in the modulation of synaptic transmission in this nucleus, we coupled whole-cell patch clamp recordings from striatal spiny neurons to the focal stimulation of glutamatergic or GABAergic nerve terminals. We found that neither cocaine (1-600 M) nor amphetamine (0.3-300 M) significantly affected the glutamate-mediated EPSCs recorded from these cells. Conversely, both pharmacological agents depressed GABA-mediated IPSCs in a dose-dependent manner. This effect was mediated by the stimulation of dopamine (DA) D2 receptors since it was prevented by 3 M L-sulpiride (a DA D2-like receptor antagonist), mimicked by the DA D2-like receptor agonist quinpirole (0.3-30 M), and absent in mice lacking DA D2 receptors. A presynaptic mechanism was likely involved in this action since both cocaine and amphetamine depress GABAergic transmission by increasing paired-pulse facilitation. Cocaine and amphetamine failed to affect GABAergic IPSCs after 6-OHDA-induced nigral lesion, indicating that both drugsFollowing psychostimulant administration, markers of brain activity are altered in many areas (Stein and Fuller 1993;Lyons et al. 1996;Breiter et al. 1997), suggesting that the diverse cognitive, emotional, and motor effects of these drugs are caused by the interaction with multiple neuronal systems in the central nervous system. Increasing evidence indicates that not only cortical but also subcortical areas play a role in the cocaine-and amphetamine-mediated effects. In particular, the increased locomotor activity and stereotypy caused by psychostimulants seem to involve specifically the nucleus striatum (Kelly et al. 1975;Amalric and Koob 1993;Berke and Hyman 2000), a structure that receives virtually all the cortical information directed to the basal ganglia (Penney and Young 1983;Albin et al. 1989;McGeorge and Faull 1989;Calabresi et al. 1996 Kaneko et al. 2000). The nucleus striatum also receives profuse dopaminergic innervation from the substantia nigra and has a very high density of D1 and D2 dopamine (DA) receptors but also of D3, D4 and D5 receptors (Mansour and Watson 1995;Surmeier et al. 1996;Bordet et al. 1997;LaHoste et al. 2000). Amphetamine and cocaine cause in the striatum rapid induction of c-fos, a commonly used molecular marker for neuronal activity. Interestingly, this effect is sensitive to dopamine (DA) receptor blockade (Graybiel et al. 1990;Moratalla et al. 1993), suggesting that increased release of DA in the striatum is responsible, at least in part, for the action of these drugs. In this regard, while the full diversity of drug effects is mediated by multiple neurotransmitters acting in multiple brain regions, most drugs abused by humans share the common property of increasing DA release in this brain area (Di Chiara and Imperato 1988; Kuczenshi et al. 1991;Yamamoto and Spanos 1988;Koob et al. 1998;Ito et al. 2000). Cocaine increases DA availability in th...

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Section: Discussionsupporting

confidence: 78%

Cocaine and Amphetamine Depress Striatal GABAergic Synaptic Transmission through D2 Dopamine Receptors

Centonze

Picconi

Baunez

et al. 2002

Neuropsychopharmacology

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“…DA can influence the activity of striatal spiny neurons by modulating voltage-dependent ion channels as well as excitatory and inhibitory synaptic inputs (Nicola et al, 2000). Although this generalization does not consistently apply, some studies have found that activation of D 1 -like receptors increases and D 2 -like receptors decreases membrane excitability of striatal neurons (Gonon, 1997;Hernandez-Lopez et al, 2000;West and Grace, 2002). The state of the neurons also influences the effects caused by DA.…”

Section: Dopamine Receptors In the Striatummentioning

confidence: 99%

Cholinergic interneuron characteristics and nicotinic properties in the striatum

2002

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ABSTRACT:The neostriatum (dorsal striatum) is composed of the caudate and putamen. The ventral striatum is the ventral conjunction of the caudate and putamen that merges into and includes the nucleus accumbens and striatal portions of the olfactory tubercle. About 2% of the striatal neurons are cholinergic. Most cholinergic neurons in the central nervous system make diffuse projections that sparsely innervate relatively broad areas. In the striatum, however, the cholinergic neurons are interneurons that provide very dense local innervation. The cholinergic interneurons provide an ongoing acetylcholine (ACh) signal by firing action potentials tonically at about 5 Hz. A high concentration of acetylcholinesterase in the striatum rapidly terminates the ACh signal, and thereby minimizes desensitization of nicotinic acetylcholine receptors. Among the many muscarinic and nicotinic striatal mechanisms, the ongoing nicotinic activity potently enhances dopamine release. This process is among those in the striatum that link the two extensive and dense local arbors of the cholinergic interneurons and dopaminergic afferent fibers. During a conditioned motor task, cholinergic interneurons respond with a pause in their tonic firing. It is reasonable to hypothesize that this pause in the cholinergic activity alters action potential dependent dopamine release. The correlated response of these two broad and dense neurotransmitter systems helps to coordinate the output of the striatum, and is likely to be an important process in sensorimotor planning and learning.

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“…Also, we cannot exclude that posttranslational modification (phosphorylation), which greatly affect NGFI-B activity (Maira et al, 2003), of pre-existing NGFI-B or de novo haloperidol-induced NGFI-B may play a role in the effects observed here. Other signaling pathways such as those implicating phospholipase C, intracellular calcium stores and protein kinase C (PKC) might also be involved (see Hernandez-Lopez et al, 2000). In addition, modulation of NGFI-B expression might also be indirect through modulation of glutamate neurotransmission by neuroleptic drugs (Leveque et al, 2000).…”

Section: Ngfi-b(+/+) Ngfi-b(-/-) Ngfi-b(+/+) Ngfi-b(-/mentioning

confidence: 99%

The Transcription Factor NGFI-B (Nur77) and Retinoids Play a Critical Role in Acute Neuroleptic-Induced Extrapyramidal Effect and Striatal Neuropeptide Gene Expression

Éthier

Beaudry

St-Hilaire

et al. 2003

Neuropsychopharmacol

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Despite extensive investigation, the cellular mechanisms responsible for neuroleptic actions remain elusive. We have previously shown that neuroleptics modulated the expression of some members of the ligand-activated transcription factors (nuclear receptors) including the nerve-growth factor inducible gene B (NGFI-B or Nur77) and retinoid X receptor (RXR) isoforms. Using genetic and pharmacological approaches, we investigated the role of NGFI-B and retinoids in acute behavioral and biochemical responses to dopamine antagonists. NGFI-B knockout (KO) mice display a profound alteration of haloperidol-induced catalepsy and striatal neuropeptide gene expression. Haloperidol-induced increase of striatal enkephalin mRNA is totally abolished in NGFI-B KO mice whereas the increase of neurotensin mRNA expression is reduced by 50%. Interestingly, catalepsy induced by raclopride, a specific dopamine D 2 /D 3 antagonist is completely abolished in NGFI-B-deficient mice whereas the cataleptic response to SCH 23390, a dopamine D 1 agonist, is preserved. Accordingly, the effects of haloperidol on striatal c-fos, Nor-1, and dynorphin mRNA expression are also preserved in NGFI-B-deficient mice. The cataleptic response and the increase of enkephalin mRNA expression induced by haloperidol can also be suppressed by administration of retinoid ligands 9-cis retinoic acid and docosahexaenoic acid. In addition, we demonstrate that haloperidol enhances colocalization of NGFI-B and RXRg1 isoform mRNAs, suggesting that both NGFI-B and a RXR isoform are highly coexpressed after haloperidol administration. Our data demonstrate, for the first time, that NGFI-B and retinoids are actively involved in the molecular cascade induced by neuroleptic drugs.

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D₂Dopamine Receptors in Striatal Medium Spiny Neurons Reduce L-Type Ca²⁺Currents and Excitability via a Novel PLCβ1–IP₃–Calcineurin-Signaling Cascade

Cited by 461 publications

References 57 publications

Cocaine and Amphetamine Depress Striatal GABAergic Synaptic Transmission through D2 Dopamine Receptors

Cocaine and Amphetamine Depress Striatal GABAergic Synaptic Transmission through D2 Dopamine Receptors

Cholinergic interneuron characteristics and nicotinic properties in the striatum

The Transcription Factor NGFI-B (Nur77) and Retinoids Play a Critical Role in Acute Neuroleptic-Induced Extrapyramidal Effect and Striatal Neuropeptide Gene Expression

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