Midbrain dopaminergic neurons from postnatal rat in long-term primary culture

Cardozo, David Lopes

doi:10.1016/0306-4522(93)90342-d

Cited by 68 publications

(36 citation statements)

References 52 publications

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“…Furthermore, our results show that there must be sufficient DA released by ongoing activity in static cultures to activate D 2 autoreceptors. Nanomolar concentrations of DA acutely hyperpolarize cultured DA neurons (Cardozo, 1993). However, the sensitivity to DA is expected to vary among D 2 receptor-induced effects depending on diverse downstream signaling pathways, the different cellular targets used for controlling channel gating and number, and spare receptors.…”

Section: Discussionmentioning

confidence: 99%

D₂Autoreceptors Chronically Enhance Dopamine Neuron Pacemaker Activity

Hahn

Kullmann²,

Horn³

et al. 2006

J. Neurosci.

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Activation of D 2 autoreceptors on midbrain dopamine neurons has been shown previously to acutely open Kϩ channels to inhibit intrinsically generated pacemaker activity. Here we report that D 2 autoreceptors act chronically to produce an opposite action: to increase the speed and regularity of repetitive action potential firing. Voltage-, current-, and dynamic-clamp experiments, using conventional whole-cell and perforated patch-clamp recording, with cultured rat midbrain dopamine neurons show that a change in the number of functional A-type K ϩ channels alters firing rate and susceptibility to irregularity produced by other channels. cAMP and protein kinase A mediate the long-term action of D 2 receptors in a manner that counters the short-term effect of this signaling pathway on K ϩ channel gating. We conclude that D 2 autoreceptors, in addition to mediating acute negative feedback, are responsible for long-term enhancement of the rate and fidelity of dopamine neuron pacemaker activity.

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Section: Discussionmentioning

confidence: 99%

D₂Autoreceptors Chronically Enhance Dopamine Neuron Pacemaker Activity

Hahn

Kullmann²,

Horn³

et al. 2006

J. Neurosci.

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“…Primary cultures of ventral mesencephalon were prepared from rats aged from 1 to 3 d according to previously described protocols (Bourque and Trudeau, 2000;Michel and Trudeau, 2000;Congar et al, 2002) derived from Cardozo (1993) and Sulzer et al (1998). Briefly, animals were cryoanesthetized, brains were rapidly removed, and a coronal section (ϳ1 mm thick) was prepared at the level of the midbrain flexure.…”

Section: Methodsmentioning

confidence: 99%

Role of Calcium in Neurotensin-Evoked Enhancement in Firing in Mesencephalic Dopamine Neurons

St-Gelais¹,

Legault²,

Bourque³

et al. 2004

J. Neurosci.

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“…Among the 104 cells isolated, 83 were large multipolar, 5 were small bipolar and 16 were atypical cells. Although many papers have already reported that dopaminergic neurons have a large body and multiple neurites (Grace and Bunny, 1983a;Grace and Bunny, 1983b;Grace, 1988;Cardozo, 1993;Chung et al, 2000), in order to confirm whether the large multipolar cells are dopaminergic, we stained cells with the antibody (PelFreez, USA) for tyrosine hydroxylase (TH), which is the main enzyme for synthesizing dopamine. After incubation with secondary antibodies tagged with FITC, we found that 76 out of 83 large multipolar cells (91.5%) showed strong fluorescence intensity as shown in Fig.…”

Section: Identification Of Dopamine Neuronsmentioning

confidence: 99%

“…Spontaneous firing activities and cytosolic Ca 2+ concentration It is well known that dopamine neurons in substantia nigra generate spontaneous firing in vivo, in vitro and even in isolated cells (Grace and Bunney, 1983a;Grace and Bunney, 1983b;Grace, 1988;Cardozo, 1993;Uchida et al, 2002). Thus, in order to test whether the neurons we isolated produce SAPs, we used patch-clamp techniques.…”

Section: Identification Of Dopamine Neuronsmentioning

confidence: 99%

“…Subthalamic and pedunculopontine nuclei and neurons in prefrontal cortex provide glutamatergic inputs to the dopamine neurons and can regulate firing patterns and increase their frequency of SAPs (Cardozo, 1993;Meltzer et al, 1997;Kitai et al, 1999;Grillner and Mercuri, 2002). In addition to these inputs, dopamine neurons can be tonically exposed to glutamate at variable concentrations owing to ambient glutamate levels, local synaptic activities of glutamatergic neurons and pathologic conditions such as seizures, injuries, and hypoxia (Benveniste et al, 1984;Lerma et al, 1986;Sah et al, 1989;HerreraMarschitz et al, 1996;Obrenovitch and Urenjak, 1997).…”

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confidence: 99%

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Glutamate-mediated [Ca2+]c dynamics in spontaneously firing dopamine neurons of the rat substantia nigra pars compacta

Choi

Kim

Uhm

et al. 2003

Journal of Cell Science

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The mechanism by which glutamate regulates the cytosolic free Ca2+ concentration ([Ca2+]c) in spontaneously firing dopamine neurons is not clear. Thus we have investigated the glutamate-mediated [Ca2+]c dynamics in the acutely isolated dopamine neurons from the rat substantia nigra pars compacta by measuring [Ca2+]c and spontaneously occurring action potentials (SAPs). The freshly isolated dopamine neurons showed tetrodotoxin(TTX)-sensitive spontaneous firing of 2-3 Hz and the resting[Ca2+]c decreased with abolition of the SAPs. The level of [Ca2+]c was affected by the spontaneous firing rate. In the presence of the Na+ channel antagonist, TTX (0.5 μM),glutamate increased [Ca2+]c by activating different glutamate receptors depending on the glutamate concentration used. Addition of glutamate at low concentrations (<3 μM) raised[Ca2+]c mainly by activating metabotropic glutamate receptors (mGluR), whereas at high concentrations (>10 μM) it raised[Ca2+]c mainly by activating AMPA/kainate receptors. The contribution of NMDA receptors to the glutamate-mediated[Ca2+]c rises was largest at intermediate concentrations of glutamate. Activation of mGluR elicited a Ca2+ release from intracellular Ca2+ stores and continuous Ca2+ influx out of the cell. The spontaneous firing activities were highly enhanced by submicromolar levels of glutamate and abolished at levels above 10 μM. From these results, we conclude that at low glutamate concentrations the[Ca2+]c in the dopamine neurons is mainly governed by mGluR and the firing activities, whose rate is regulated at submicromolar glutamate concentrations, but at higher glutamate concentrations[Ca2+]c is dominantly affected by AMPA/kainate receptors.

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Midbrain dopaminergic neurons from postnatal rat in long-term primary culture

Cited by 68 publications

References 52 publications

D₂Autoreceptors Chronically Enhance Dopamine Neuron Pacemaker Activity

D₂Autoreceptors Chronically Enhance Dopamine Neuron Pacemaker Activity

Role of Calcium in Neurotensin-Evoked Enhancement in Firing in Mesencephalic Dopamine Neurons

Glutamate-mediated [Ca2+]c dynamics in spontaneously firing dopamine neurons of the rat substantia nigra pars compacta

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Midbrain dopaminergic neurons from postnatal rat in long-term primary culture

Cited by 68 publications

References 52 publications

D2Autoreceptors Chronically Enhance Dopamine Neuron Pacemaker Activity

D2Autoreceptors Chronically Enhance Dopamine Neuron Pacemaker Activity

Role of Calcium in Neurotensin-Evoked Enhancement in Firing in Mesencephalic Dopamine Neurons

Glutamate-mediated [Ca2+]c dynamics in spontaneously firing dopamine neurons of the rat substantia nigra pars compacta

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D₂Autoreceptors Chronically Enhance Dopamine Neuron Pacemaker Activity

D₂Autoreceptors Chronically Enhance Dopamine Neuron Pacemaker Activity