Iontophoretically applied dopamine depolarizes and hyperpolarizes the membrane of cat caudate neurons

Herrling, Paul L.; Hull, C.D.

doi:10.1016/0006-8993(80)90896-3

Cited by 166 publications

(43 citation statements)

References 38 publications

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“…This suggests that DAergic inputs may be able to modulate excitatory cortical/ thalamic inputs. The loss of DAergic input, which appears to be inhibitory at least on a subpopulation of striatal neurons (Herrling and Hull, 1980) might allow more striatal neurons to respond to stimulation of the cortex or thalamus and perhaps lower the stimulation threshold needed to elicit a response, as we observed in symptomatic animals. In recovered animals, a return of inhibitory modulation of striatal neurons (via increased ECF concentrations of DA) might have contributed to the return to relatively normal levels of striatal responsiveness to stimulation of monosynaptic inputs.…”

Section: Discussionmentioning

confidence: 70%

Response of caudate neurons to stimulation of intrinsic and peripheral afferents in normal, symptomatic, and recovered MPTP-treated cats

Rothblat

Schneider

1993

J. Neurosci.

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Cat caudate nucleus (CD) neurons were tested for changes in spontaneous activity, response to peripheral sensory stimuli (tactile, auditory, and visual), and electrical stimulation of monosynaptic afferents (pericruciate cortex and nucleus centralis lateralis) in normal cats and in the same cats after induction of and spontaneous recovery from parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). After normal baseline data were collected, cats were given MPTP (7.5 mg/kg, 5–7 d) to induce a parkinsonian syndrome consisting of rigidity, akinesia, and decreased orienting to sensory stimuli. During this symptomatic period, the mean spontaneous activity of CD units increased (6.20 spikes/sec vs 2.25 spikes/sec in normal cats). In these same animals, the percentage of units responding to peripheral sensory stimulation was significantly decreased (compared to normal) while the percentage of units responding to electrical stimulation of monosynaptic afferents increased. By 6 weeks after MPTP administration, cats had recovered gross motor and sensorimotor function and CD unit recordings were reinitiated. In functionally recovered animals, all electrophysiological measures returned to levels resembling those seen in normal animals. These data suggest that the processing of peripheral sensory information is an important part of basal ganglia function and that the sensory responsiveness of the CD may reflect the overall motor condition of the animal. The changes observed in the responsiveness of CD neurons to direct electrical stimulation of monosynaptic afferents may indicate that the defect in the processing of polysynaptic sensory information observed in the striatum in parkinsonian animals may be occurring, at least in part, extrastriatally.

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Section: Discussionmentioning

confidence: 70%

Response of caudate neurons to stimulation of intrinsic and peripheral afferents in normal, symptomatic, and recovered MPTP-treated cats

Rothblat

Schneider

1993

J. Neurosci.

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“…On the other hand, Greengard's group (7) has shown that in isolated neostriatal neurons, DI and D2 agonists can act synergistically to suppress Na+/K+ ATPase activity. 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).…”

Section: Jam) (B)mentioning

confidence: 99%

“…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%

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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“…It has also been found that in a certain area of the CNS there are abundant serotonergic axon-terminals or varicosities in the vicinity of catecholaminergic synapses (GALAS et a!.,1974;DESCARRIES, 1976, 1979;BOBILLIER et al, 1976;MOORE and BLOOM, 1978;SIMoN et al, 1979;STE-INBUSCH, 1981). The DA receptor of the pyramidal cell in hippocampus is the only receptor to be identified in mammals as being of the DH-type (BENARDO and PRINCE, 1982), although many neurons in the cortex and striatum have been shown to exhibit both inhibitory and excitatory responses to DA (HERRLING and HULL, 1980;HERRLING, 1981;BERNARDI et al, 1982).…”

Section: ) Effects Of Other Indole Derivatives On the Dahk-type Of Rmentioning

confidence: 99%

Blocking effect of serotonin on inhibitory dopamine receptor activity of Aplysia ganglion cells.

Shozushima

1984

Jpn.J.Physiol

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1) The abdominal ganglion of Aplysia includes neurons with a characteristic dopamine (DA) receptor, the activation of which induces a marked hyperpolarization with a specific increase in the permeability of the membrane to KtThe DA receptor of this type is called the "H K-type." 2) A 2-min exposure to 1,IM serotonin (5-HT) had little effect on the resting membranes with the receptor of HK-type, but significantly depressed the responses to 10 µM DA. The depressing effect of 5-HT on this type of response was completely reversible after a 15-min washing with normal artificial Aplysia blood. 3) Lineweaver-Burke type plotting of the DA-induced responses showed a systematic shift of the straight lines when the concentration of 5-HT was increased; the slope of the line became steeper but the intercept on the ordinate remained unchanged. 4) The dose-inhibition curves, in which relative responses to a given [DA] were plotted against log [5-HT], showed a parallel shift toward the right when the concentration of DA increased. 5) These findings suggest that 5-HT competes with DA for common binding sites at the DA receptor of HK-type, and that the blockade is not due to the interaction of 5-HT with K+-channels in the receptor membrane. 6) The effect of other indole derivatives suggests that the DA receptor of HK-type includes anionic and cationic sites to which the NH2 group and 5-HO group of 5-HT could specifically bind, thus exhibiting competitive blockade.

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Iontophoretically applied dopamine depolarizes and hyperpolarizes the membrane of cat caudate neurons

Cited by 166 publications

References 38 publications

Response of caudate neurons to stimulation of intrinsic and peripheral afferents in normal, symptomatic, and recovered MPTP-treated cats

Response of caudate neurons to stimulation of intrinsic and peripheral afferents in normal, symptomatic, and recovered MPTP-treated cats

Dopamine receptor subtypes colocalize in rat striatonigral neurons.

Blocking effect of serotonin on inhibitory dopamine receptor activity of Aplysia ganglion cells.

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