Dopamine and GABA receptors in cultured substantia nigra neurons: correlation of electrophysiology and immunocytochemistry

Kim, K.-M; Nakajima, Shigehiro; Nakajima, Yoshiaki

doi:10.1016/s0306-4522(96)00585-4

Cited by 24 publications

(14 citation statements)

References 35 publications

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“…In the present and other studies both GABA A and GABA B receptors were located in DA cells (Kim et al, 1997;Wirtsshafter and Sheppard, 2001;Schlesinger et al, 2004) as well as in glial cells and other cell populations such as serotonergic cells (Wirtsshafter and Sheppard, 2001), which have been shown to regulate generation of DA cells from proliferating neurospheres of mesencephalic precursors. We have previously shown that elimination of serotonergic cells or inhibition of serotonin synthesis induces a marked increase in generation of DA cells from proliferating neurospheres of mesencephalic precursors (Rodriguez-Pallares et al, 2003), and it has been reported that GABA A receptor antagonists significantly reduced the survival of serotonergic neurons in primary cultures from rat brainstem (Liu et al, 1997).…”

Section: Discussionsupporting

confidence: 63%

Effects of GABA and GABA receptor inhibition on differentiation of mesencephalic precursors into dopaminergic neurons in vitro

Rodríguez‐Pallares

Guerra

Labandeira‐Garcia

2007

Developmental Neurobiology

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ABSTRACT:Neurotransmitters have been shown to control CNS neurogenesis, and GABA-mediated signaling is thought to be involved in the regulation of nearly all key developmental stages. Generation of dopaminergic (DA) neurons from stem/precursor cells for cell therapy in Parkinson's disease has become a major focus of research. However, the possible effects of GABA on generation of DA neurons from proliferating neurospheres of mesencephalic precursors have not been studied. In the present study, GABA A , and GABA B receptors were found to be located in DA cells. Treatment of cultures with GABA did not cause significant changes in generation of DA cells from precursors. However, treatment with the GABA A receptor antagonist bicuculline (10 À5 M) led to a significant increase in the number DA cells, and treatment with the GABA B receptor antagonist CGP 55845 (10 À5 M) to a significant decrease. Simultaneous treatment with bicuculline and CGP 55845 did not induce significant changes. Apoptotic cell death studies and bromodeoxyuridine immunohistochemistry indicated that the aforementioned differences in generation of DA neurons are not due to changes in survival or proliferation of DA cells, but rather to increased or decreased differentiation of mesencephalic precursors towards the DA phenotype. The results suggest that these effects are exerted via GABA receptors located on DA precursors, and are not an indirect consequence of effects on the serotonergic or glial cell population. Administration of GABA A receptor antagonists in the differentiation medium may help to obtain higher rates of DA neurons for potential use in cell therapy for Parkinson's disease. '

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Section: Discussionsupporting

confidence: 63%

Effects of GABA and GABA receptor inhibition on differentiation of mesencephalic precursors into dopaminergic neurons in vitro

Rodríguez‐Pallares

Guerra

Labandeira‐Garcia

2007

Developmental Neurobiology

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“…It should also be possible to conduct electrophysiological studies on these preparations 33,34 . These cultures can identify pre-candidate neuroprotective molecules and help to characterize DA neurons properties, while minimizing the number of animals used.…”

Section: Discussionmentioning

confidence: 99%

Primary Culture of Mouse Dopaminergic Neurons

Gaven

Marin

Claeysen

2014

JoVE

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Dopaminergic neurons represent less than 1% of the total number of neurons in the brain. This low amount of neurons regulates important brain functions such as motor control, motivation, and working memory. Nigrostriatal dopaminergic neurons selectively degenerate in Parkinson's disease (PD). This progressive neuronal loss is unequivocally associated with the motors symptoms of the pathology (bradykinesia, resting tremor, and muscular rigidity). The main agent responsible of dopaminergic neuron degeneration is still unknown. However, these neurons appear to be extremely vulnerable in diverse conditions. Primary cultures constitute one of the most relevant models to investigate properties and characteristics of dopaminergic neurons. These cultures can be submitted to various stress agents that mimic PD pathology and to neuroprotective compounds in order to stop or slow down neuronal degeneration. The numerous transgenic mouse models of PD that have been generated during the last decade further increased the interest of researchers for dopaminergic neuron cultures. Here, the video protocol focuses on the delicate dissection of embryonic mouse brains. Precise excision of ventral mesencephalon is crucial to obtain neuronal cultures sufficiently rich in dopaminergic cells to allow subsequent studies. This protocol can be realized with embryonic transgenic mice and is suitable for immunofluorescence staining, quantitative PCR, second messenger quantification, or neuronal death/survival assessment. Video LinkThe video component of this article can be found at

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“…As noted in the Introduction, both GABA B receptors and D2 dopamine receptors are coupled to G-protein-linked inwardly rectifying potassium channels (GIRKs) (Kim, et al, 1997; Lacey, et al, 1988). It may be that GIRKs are the common point of action of GABA B receptors and dopamine D2 receptors, and that desensitization of the effect of baclofen and dopamine are produced by a reduction of GIRK responsiveness.…”

Section: Discussionmentioning

confidence: 99%

Reversal of inhibition of putative dopaminergic neurons of the ventral tegmental area: Interaction of GABAB and D2 receptors

et al. 2012

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Neurons of the ventral tegmental area (VTA) are critical in the rewarding and reinforcing properties of drugs of abuse. Desensitization of VTA neurons to moderate extracellular concentrations of dopamine (DA) is dependent on protein kinase C (PKC) and intracellular calcium levels. This desensitization is called DA inhibition reversal (DIR), as it requires concurrent activation of D2 and D1-like receptors; activation of D2 receptors alone does not result in desensitization. Activation of other G-protein linked receptors can substitute for D1 activation. Like D2 receptors, GABAB receptors in the VTA are coupled to G-protein-linked potassium channels. In the present study, we examined interactions between a GABAB agonist, baclofen, and dopamine agonists, dopamine and quinpirole, to determine whether there was some interaction in the processes of desensitization of GABAB and D2 responses. Long-duration administration of baclofen alone produced reversal of the baclofen-induced inhibition indicative of desensitization, and this desensitization persisted for at least 60 min after baclofen washout. Desensitization to baclofen was dependent on protein kinase C. Dopamine inhibition was reduced for 30 min after baclofen-induced desensitization and conversely, the magnitude of baclofen inhibition was reduced for 30 min by long-duration application of dopamine, but not quinpirole. These results indicate that D2 and GABAB receptors share some protein kinase C-dependent mechanisms of receptor desensitization.

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Dopamine and GABA receptors in cultured substantia nigra neurons: correlation of electrophysiology and immunocytochemistry

Cited by 24 publications

References 35 publications

Effects of GABA and GABA receptor inhibition on differentiation of mesencephalic precursors into dopaminergic neurons in vitro

Effects of GABA and GABA receptor inhibition on differentiation of mesencephalic precursors into dopaminergic neurons in vitro

Primary Culture of Mouse Dopaminergic Neurons

Reversal of inhibition of putative dopaminergic neurons of the ventral tegmental area: Interaction of GABAB and D2 receptors

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