Excitatory and inhibitory effects of dopamine on neuronal activity of the caudate nucleus neurons in vitro

Akaike, Akinori; Ohno, Yukihiro; Sasa, Masashi; Takaori, Shuji

doi:10.1016/0006-8993(87)90094-1

Cited by 150 publications

(80 citation statements)

References 27 publications

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“…Physiological studies using dopamine have revealed complex response patterns of excitation and inhibition of evoked activity (8,34) that were attributed to indirect effects or coactivation of Di and D2 receptors. However, the use of receptor-selective agonists has clarified the picture only for the DI receptor-mediated modulation, for which a reduction in evoked discharge has consistently been reported (9)(10)(11)35). Calabresi et al (35) attributed this effect to a reduction of Na+ current, as we have confirmed.…”

Section: Jam) (B)supporting

confidence: 74%

“…This model of receptor segregation is difficult to reconcile with much of the biochemical and physiological literature addressing the effects of dopamine in the neostriatum (6)(7)(8)(9)(10)(11)(12). Gerfen et al's hypothesis implicitly argues that the appearance of convergence is a consequence of the failure to separate direct postsynaptic effects from indirect effects mediated by adjacent neurons.…”

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confidence: 99%

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Dopamine receptor subtypes colocalize in rat striatonigral neurons.

Surmeier

Eberwine

Wilson

et al. 1992

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

337

247

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Dopaminergic neurons of the substantia nigra provide one of the major neuromodulatory Inputs to the neostriatum. Recent in situ hybridization experiments have suggested that postsynaptic dopamine receptors are segregated in striatonigral and striatopallidal neurons. We have tested this hypothesis in acutely isolated, retrogradely labeled striatonigral neurons by examining the neuromodulatory effects of selective dopaminergic agonists on Na currents and by probing single-cell antisense RNA populations with dop receptor cDNAs. In most of the neurons examined (20/31), the application of the Di dopamine receptor agonist SKF 38393 reduced evoked whole-cell Na+ current. The D2 agonists quinpirole and bromocriptine had mixed effects; in most neurons (23/42), whole-cell Na+ currents were reduced, but in others (8/42), currents were increased. In cell-attached patch recordings, bath application of SKF 38393 decreased currents as in wholecell recordings, whereas quinpirole consistently (6/10) enhanced currents-suggesting that D2-like receptors could act through membrane delimited and non-delimited pathways. Changes in evoked current were produced by modulation of peak conductance and modest shifts in the voltage dependence of steady-state inactivation. Antisense RNA probes of dopamine receptor cDNA Southern blots consistently (5/5) revealed the presence of Di, D2, and D3 receptor mRNA in single striatonigral neurons. These rnmdings argue that, contrary to a strict receptor segregation hypothesis, many striatonigral neurons colocalize functional Di, D2, and D3 receptors.The role of the dopaminergic nigrostriatal system in controlling the excitability of neostriatal neurons has been intensely studied since it became clear that the loss of this innervation was responsible for the psychomotor symptoms ofParkinson disease (1). Molecular cloning and hybridization studies (2, 3) have revealed that the postsynaptic actions of dopamine are mediated by a family of five G-protein-coupled receptors (D1-D5). In situ hybridization experiments of Gerfen et al. (4, 5) have suggested that two members of this family-the D1 and D2 receptors-are segregated in the two major efferent populations of the neostriatum that project to the substantia nigra and pallidum. They have inferred from their findings that these pathways can be selectively modulated by D1 and D2 agonists. In its strictest form, this hypothesis requires that striatonigral neurons express only those dopamine receptors with a D1 pharmacological profile (D1 and D5) and that striatopallidal neurons express only those receptors with a D2 profile (D2, D3, and D4).This model of receptor segregation is difficult to reconcile with much of the biochemical and physiological literature addressing the effects of dopamine in the neostriatum (6-12). Gerfen et al.'s hypothesis implicitly argues that the appearance of convergence is a consequence of the failure to separate direct postsynaptic effects from indirect effects mediated by adjacent neurons. Such a separation is virtually imp...

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Section: Jam) (B)supporting

confidence: 74%

mentioning

confidence: 99%

Dopamine receptor subtypes colocalize in rat striatonigral neurons.

Surmeier

Eberwine

Wilson

et al. 1992

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

337

247

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“…However, there are many findings that do not support such a marked chemical segregation between the putative direct and indirect pathways. First, recent studies have detected a significant number of striatal neurons that express both D1 and D2 receptors (15)(16)(17)(18)(19), as well as enkephalin and substance P (20)(21)(22). Second, although GPe is markedly enriched in enkephalin, a significant amount of this neuroactive peptide also occurs in the SNr of primates (23,24).…”

Section: Dopaminergic Receptors and Striatal Peptidesmentioning

confidence: 99%

The striatofugal fiber system in primates: A reevaluation of its organization based on single-axon tracing studies

Lévesque

Parent

2005

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

174

165

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The current model of basal ganglia rests on the idea that the striatofugal system is composed of two separate (direct and indirect) pathways originating from distinct cell populations in the striatum. The striatum itself is divided into two major compartments, the striosomes and the matrix, which differ by their neurochemical makeup and input͞output connections. Here, neurons located in either striosomes or the extrastriosomal matrix in squirrel monkeys were injected with biotin dextran amine, and their labeled axons were entirely reconstructed with a camera lucida. Twenty-four of 27 reconstructed axons arborized into the three main striatal targets (external pallidum, globus pallidus, and substantia nigra pars reticulata), a finding that is at odds with the concept of a dual striatofugal system. Axons of striosomal neurons formed several columnar terminal fields in the substantia nigra pars reticulata. These data indicate that the substantia nigra pars compacta is neither the only nor the main target of striosomal neurons, a finding that calls for a reevaluation of the organization of the striatonigral projection system. anatomy ͉ basal ganglia ͉ matrix ͉ striatum ͉ striosomes T he striatum is the largest and main integrative component of the basal ganglia. It is often the site of massive cell losses or major transmitter deficits that lead to severe motor disorders, such as the excess of involuntary movements (hyperkinesia) encountered in Huntington's disease or the poverty of movements (hypokinesia) that typifies Parkinson's disease (1, 2). The striatal projection system is currently viewed as arising from two distinct but intermingled neuronal populations. A first set of striatal projection neurons targets the internal segment of the globus pallidus (GPi) or the substantia nigra pars reticulata (SNr), and the second set is directed at the external pallidal segment (GPe). These projections have been referred to as the direct and indirect striatofugal pathways (3). The direct pathway is thought to originate from GABAergic neurons that coexpress substance P and͞or dynorphin and project monosynaptically to the GPi͞SNr. The indirect pathway is believed to arise from GABAergic striatal neurons that coexpress enkephalin and project to the GPi͞SNr complex via relays in the GPe and the subthalamic nucleus.The striatum can also be divided into two compartments: the striosomes and the surrounding extrastriosomal matrix, which are known to have distinct chemical compositions and connections (4 -6). The function of this compartmentalization is still poorly understood, but anatomical studies in rats have shown differential relations of these two compartments with the substantia nigra (SN). The matrix is believed to receive inputs from sensory and motor cortical areas and to project to the SNr, whereas striosomes are thought to receive inputs from limbic cortical areas and to project to the SN pars compacta (SNc) (4,7,8). However, these concepts derive mainly from studies undertaken in rodents by means of bulk injections of...

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“…In particular, D 1a receptor mRNA is found in substance P-expressing (SP) neurons projecting to the substantia nigra, whereas D 2 receptor mRNA is found in enkephalin-expressing (ENK) neurons projecting exclusively to the globus pallidus. More recent immunocytochemical work supports this conclusion (Hersch et al, 1995), although others have reported significant degrees of receptor protein colocalization .Functional studies, on the other hand, repeatedly have observed responses to D 1 and D 2 class agonists that are difficult to explain if these receptor classes are not colocalized (Uchimura et al, 1986;Akaike et al, 1987;Cepeda et al, 1993; for review, see Surmeier et al, 1993). The most compelling evidence comes from patch-clamp studies of acutely isolated neostriatal neuronswhere synaptic interactions have been removed-showing neuromodulatory effects of both D 1 and D 2 class agonists in the same cell (Surmeier et al, 1992).…”

mentioning

confidence: 95%

“…Functional studies, on the other hand, repeatedly have observed responses to D 1 and D 2 class agonists that are difficult to explain if these receptor classes are not colocalized (Uchimura et al, 1986;Akaike et al, 1987;Cepeda et al, 1993; for review, see Surmeier et al, 1993). The most compelling evidence comes from patch-clamp studies of acutely isolated neostriatal neuronswhere synaptic interactions have been removed-showing neuromodulatory effects of both D 1 and D 2 class agonists in the same cell (Surmeier et al, 1992).…”

mentioning

confidence: 99%

Coordinated Expression of Dopamine Receptors in Neostriatal Medium Spiny Neurons

Surmeíer

Yan

Song

1997

Advances in Pharmacology

164

196

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In recent years, the distribution of dopamine receptor subtypes among the principal neurons of the neostriatum has been the subject of debate. Conventional anatomical and physiological approaches have yielded starkly different estimates of the extent to which D 1 and D 2 class dopamine receptors are colocalized. One plausible explanation for the discrepancy is that some dopamine receptors are present in physiologically significant numbers, but the mRNA for these receptors is not detectable with conventional techniques. To test this hypothesis, we examined the expression of DA receptors in individual neostriatal neurons by patch-clamp and RT-PCR techniques. Because of the strong correlation between peptide expression and projection site, medium spiny neurons were divided into three groups on the basis of expression of mRNA for enkephalin (ENK) and substance P (SP The signaling pathways activated by dopamine in the neostriatum have been the subject of intense study since it was discovered that the loss of dopamine leads to the psychomotor symptoms of Parkinson's disease (Hornykiewcz, 1973). Subsequently, several other common psychomotor disorders, including schizophrenia and Tourette's syndrome, have been linked to alterations in neostriatal dopaminergic signaling (Nemeroff and Bissette, 1988;Erenberg, 1992). In recent years, significant progress has been made in characterizing the membrane receptors transducing the signals of dopamine in the neostriatum and the brain in general. How these receptors are distributed among the principal neuronal cell types in the neostriatum has been the subject of debate (Surmeier et al., 1993). This controversy stems primarily from discrepancies in the results obtained from functional studies on the one hand and anatomical studies on the other. The most compelling anatomical data are in situ hybridization studies suggesting that D 1a and D 2 mRNA are segregated primarily in the two major efferent neostriatal populations (Gerfen, 1992; LeMoine and Bloch, 1995). In particular, D 1a receptor mRNA is found in substance P-expressing (SP) neurons projecting to the substantia nigra, whereas D 2 receptor mRNA is found in enkephalin-expressing (ENK) neurons projecting exclusively to the globus pallidus. More recent immunocytochemical work supports this conclusion (Hersch et al., 1995), although others have reported significant degrees of receptor protein colocalization .Functional studies, on the other hand, repeatedly have observed responses to D 1 and D 2 class agonists that are difficult to explain if these receptor classes are not colocalized (Uchimura et al., 1986;Akaike et al., 1987;Cepeda et al., 1993; for review, see Surmeier et al., 1993). The most compelling evidence comes from patch-clamp studies of acutely isolated neostriatal neuronswhere synaptic interactions have been removed-showing neuromodulatory effects of both D 1 and D 2 class agonists in the same cell (Surmeier et al., 1992). In this study, it was also shown that neurons projecting axons to the substantia nigra coexp...

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Excitatory and inhibitory effects of dopamine on neuronal activity of the caudate nucleus neurons in vitro

Cited by 150 publications

References 27 publications

Dopamine receptor subtypes colocalize in rat striatonigral neurons.

Dopamine receptor subtypes colocalize in rat striatonigral neurons.

The striatofugal fiber system in primates: A reevaluation of its organization based on single-axon tracing studies

Coordinated Expression of Dopamine Receptors in Neostriatal Medium Spiny Neurons

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