Dopamine agonists increase pallidal unit activity: Attenuation by agonist pretreatment and anesthesia

Bergstrom, Debra A.; Bromley, Susan D.; Walters, Judith R.

doi:10.1016/0014-2999(84)90309-1

Cited by 73 publications

(30 citation statements)

References 26 publications

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“…Thus, if striatal D2-like receptors are involved in the effects of L-DOPA, their role would be opposite to that played by DA autoreceptors. The finding that this indirect striatonigral pathway is largely inactivated in anesthetized animals (Bergstrom et al, 1984) further supports the suggestion that the pathway is not critical to the effects of L-DOPA observed in the present study. Finally, SN non-DA neurons receive inputs from both the direct and indirect striatonigral pathways (Kravitz et al, 2010).…”

Section: Discussionsupporting

confidence: 90%

“…Apomorphine is a mixed D1 and D2-like receptor agonist (Seeman, 2007). At low doses (Յ50 g/kg), apomorphine inhibits the firing of DA neu- jpet.aspetjournals.org rons without significantly affecting cells postsynaptic to DA terminals (Skirboll et al, 1979;Bergstrom et al, 1984). Other D2-like receptor agonists tested exhibit similar properties, including the antiparkinsonian agents pergolide and pramipexole (Carlson et al, 1987;Piercey et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

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Effects of l-DOPA on Nigral Dopamine Neurons and Local Field Potential: Comparison with Apomorphine and Muscimol

Xu¹,

Karain²,

Brantley³

et al. 2011

J Pharmacol Exp Ther

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L-DOPA is more effective than direct dopamine (DA) agonists in relieving the motor deficits in Parkinson's disease. Using in vivo recording, we compared the effect of L-DOPA and the direct DA agonist apomorphine on DA neurons in rat substantia nigra (SN). L-DOPA (50 -100 mg/kg i.v.) decreased the firing rate as well as the variability and slow oscillation (SO) of firing. All effects were blocked by raclopride and mimicked by quinpirole, suggesting that they are mediated through D2-like receptors. Autoreceptor-selective doses of apomorphine (5-20 g/kg i.v.) also inhibited all three parameters. The magnitude of the inhibition, however, was significantly greater than that induced by L-DOPA. Neither L-DOPA nor apomorphine had a consistent effect on SN local field potentials (LFPs). The GABA agonist muscimol, known to preferentially inhibit SN non-DA neurons, consistently inhibited the SO in both DA cell firing and LFPs. These results suggest that SN LFPs mainly reflect the synaptic potentials in non-DA neurons, and L-DOPA and apomorphine, unlike muscimol, affect DA neurons primarily through DA autoreceptors. DA autoreceptor activation is known to hyperpolarize DA cells by increasing the membrane conductance to K ϩ . This increase in membrane conductance would shunt synaptic input to DA neurons, thereby decreasing the variability and SO in DA cell firing. The low potency of L-DOPA to inhibit DA cell firing and reduce their responses to synaptic input may partially account for its superior therapeutic efficacy in Parkinson's disease compared with apomorphine and other direct DA agonists.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Effects of l-DOPA on Nigral Dopamine Neurons and Local Field Potential: Comparison with Apomorphine and Muscimol

Xu¹,

Karain²,

Brantley³

et al. 2011

J Pharmacol Exp Ther

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“…We focused on activity in the GPi and GPe, two important nuclei in the basal ganglia circuitry, since activity change in these nuclei has been reported in human patients. Neuronal activity was recorded in the awake state to exclude effects of general anesthesia on neuronal firing rates and patterns (Bergstom et al 1984; Keane and Biziere 1987; Löscher et al 1995). We then investigated the responses of GPi and GPe neurons evoked by cortical stimulation to elucidate the neural mechanisms underlying the symptoms exhibited by the transgenic mice.…”

Section: Introductionmentioning

confidence: 99%

Cortically Evoked Long-Lasting Inhibition of Pallidal Neurons in a Transgenic Mouse Model of Dystonia

Chiken¹,

Shashidharan²,

Nambu³

2008

J. Neurosci.

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Dystonia is a neurological disorder characterized by sustained or repetitive involuntary muscle contractions and abnormal postures. To understand the pathophysiology of dystonia, neurophysiological analyses were performed on hyperkinetic transgenic mice generated as a model of DYT1 dystonia. Abnormal muscle activity, such as coactivation of agonist and antagonist muscles and sustained muscle activation, was frequently observed in these mice. Recording of neuronal activity in the awake state revealed reduced spontaneous activity with bursts and pauses in both the external and internal segments of the globus pallidus. Motor cortical stimulation evoked responses composed of excitation and subsequent long-lasting inhibition in both pallidal segments, which were never observed in the normal mice. In addition, the somatotopic arrangements in both pallidal segments were disorganized. Long-lasting inhibition induced by cortical inputs in the internal pallidal segment may disinhibit thalamic and cortical activity, resulting in the motor hyperactivity observed in the transgenic mice.

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“…Earlier studies found two types of striatal neurons based on spike shape, Type‐I and Type‐II (Skirboll et al, ). Studies in the GP observed similar waveforms and used the same designations (Bergstrom et al, ; Kelland et al, ; Napier et al, ; Pan et al, ; Walters et al, ). In this study, all GP neurons recorded with our routinely used small‐tip electrodes fired Type‐II spikes.…”

Section: Discussionmentioning

confidence: 97%

Rat globus pallidus neurons: Functional classification and effects of dopamine depletion

Karain

Bellone

et al. 2014

Synapse

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The rat globus pallidus (GP) is homologous to the primate GP externus. Studies with injectable anesthetics suggest that GP neurons can be classified into Type-I and Type-II cells based on extracellularly recorded spike shape, or positively coupled (PC), negatively coupled (NC), and uncoupled (UC) cells based on functional connectivity with the cortex. In this study, we examined the electrophysiology of rat GP neurons using the inhalational anesthetic isoflurane which offers more constant and easily regulated levels of anesthesia than injectable anesthetics. In 130 GP neurons recorded using small-tip glass electrodes (<1 μm), all but one fired Type-II spikes (positive/negative waveform). Type-I cells were unlikely to be inhibited by isoflurane since all GP neurons also fired Type-II spikes under ketamine-induced anesthesia. When recorded with large-tip electrodes (~2 μm), however, over 70% of GP neurons exhibited Type-I spikes (negative/positive waveform). These results suggest that the spike shape, recorded extracellularly, varies depending on the electrode used and is not reliable in distinguishing Type-I and Type-II neurons. Using dual-site recording, 40% of GP neurons were identified as PC cells, 17.5% NC cells, and 42.5% UC cells. The three subtypes also differed significantly in firing rate and pattern. Lesions of dopamine neurons increased the number of NC cells, decreased that of UC cells, and significantly shifted the phase relationship between PC cells and the cortex. These results support the presence of GP neuron subtypes and suggest that each subtype plays a different role in the pathophysiology of Parkinson’s disease.

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Dopamine agonists increase pallidal unit activity: Attenuation by agonist pretreatment and anesthesia

Cited by 73 publications

References 26 publications

Effects of l-DOPA on Nigral Dopamine Neurons and Local Field Potential: Comparison with Apomorphine and Muscimol

Effects of l-DOPA on Nigral Dopamine Neurons and Local Field Potential: Comparison with Apomorphine and Muscimol

Cortically Evoked Long-Lasting Inhibition of Pallidal Neurons in a Transgenic Mouse Model of Dystonia

Rat globus pallidus neurons: Functional classification and effects of dopamine depletion

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