The Response of Subthalamic Nucleus Neurons to Dopamine Receptor Stimulation in a Rodent Model of Parkinson’s Disease

Kreiss, Deborah S.; Mastropietro, Christopher W.; Rawji, Saima S.; Walters, Judith R.

doi:10.1523/jneurosci.17-17-06807.1997

Cited by 171 publications

(122 citation statements)

References 64 publications

(83 reference statements)

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“…We have also avoided the use of urethane because of urethane-induced slow wave cortical activity that alters significantly the analysis of correlations between spike trains (Jones, 2004;Kasanetz et al, 2008;Manns et al, 2000a,b). Our finding that IPT and regular spiking neurons were the commonest types of firing under Equithesin anesthesia appears in agreement with recordings performed in the STN of unanesthetized 6-OHDA treated rats that shown also a decrease in the number of oscillatory units (Allers et al, 2000;Kreiss et al, 1997). This indicates that the active metabolites of Equithesin are unlikely to exert a strong influence upon the discharge patterns of STN units.…”

Section: Discussionsupporting

confidence: 90%

Dopamine deficiency increases synchronized activity in the rat subthalamic nucleus

Lintas¹,

Силькис²,

Albèri³

et al. 2012

Brain Research

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Abnormal neuronal activity in the subthalamic nucleus (STN) plays a crucial role in the pathophysiology of Parkinson's disease (PD). In this study we investigated changes in rat STN neuronal activity after 28 days following the injection of 6-OHDA in the substantia nigra pars compacta (SNc). This drug provoked a lesion of SNc that induced a dopamine and lesioned (n = 83) groups was similar, as well as the firing rate. In 6-OHDA treated rats we observed a significant increase (from 26% to 48%) in the number of pairs with synchronous firing. These data suggest that the synchronous activity of STN cells, provoked by loss of DA cells in SNc, is likely to be among the most significant dysfunctions in the basal ganglia of Parkinsonian patients. We raise the hypothesis that in normal conditions, DA maintains a balance between funneling information via the hyperdirect cortico-subthalamic pathway and parallel processing through the parallel cortico-basal ganglia-subthalamic pathways, both of which are necessary for selected motor behaviors..

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Section: Discussionsupporting

confidence: 90%

Dopamine deficiency increases synchronized activity in the rat subthalamic nucleus

Lintas¹,

Силькис²,

Albèri³

et al. 2012

Brain Research

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“…The present observations shed light on previously conflicting results obtained in the STN in an awake, immobilized, locally anesthetized rat preparation (Kreiss et al, 1997;Allers et al, 2005). These studies in awake animals reported a significant increase in STN firing rate but no increased burstiness in STN spike trains after dopamine lesion.…”

Section: Relevance To Awake Preparations and Faster Frequenciessupporting

confidence: 75%

“…To assess firing pattern regularity, the coefficient of variation of the interspike intervals (ISI CV) was employed; ISI CV was calculated by dividing the standard deviation of the ISIs in each 300 s epoch by the mean ISI of the epoch. In addition, spike train burstiness was assessed by the density discharge histogram method of Kanoeke and Vitek (1996), as described previously (Kreiss et al, 1997;Allers et al, 2005). A discharge density histogram with a bin width equal to twice the mean ISI was used for assessing burstiness with a burstiness index of ≥ 0.5 (see Magill et al, 2000;Wilson et al, 2004b).…”

mentioning

confidence: 99%

Phase relationships support a role for coordinated activity in the indirect pathway in organizing slow oscillations in basal ganglia output after loss of dopamine

et al. 2007

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The goal of the present study was to determine the phase relationships of the slow oscillatory activity that emerges in basal ganglia nuclei in anesthetized rats after dopamine cell lesion in order to gain insight into the passage of this oscillatory activity through the basal ganglia network. Spike train recordings from striatum, subthalamic nucleus (STN), globus pallidus (GP), and substantia nigra pars reticulata (SNpr) were paired with simultaneous local field potential (LFP) recordings from SNpr or motor cortex ipsilateral to a unilateral lesion of substantia nigra dopamine neurons in urethane anesthetized rats. Dopamine cell lesion induced a striking increase in incidence of slow oscillations (0.3-2.5 Hz) in firing rate in all nuclei. Phase relationships assessed through paired recordings using SNpr LFP as a temporal reference showed that slow oscillatory activity in GP spike trains is predominantly antiphase with oscillations in striatum, and slow oscillatory activity in STN spike trains is in-phase with oscillatory activity in cortex but predominantly antiphase with GP oscillatory activity. Taken together, these results imply that after dopamine cell lesion in urethane anesthetized rats, increased oscillatory activity in GP spike trains is shaped more by increased phasic inhibitory input from the striatum than by phasic excitatory input from STN. In addition, results show that oscillatory activity in SNpr spike trains is typically antiphase with GP oscillatory activity and in-phase with STN oscillatory activity. While these observations do not rule out additional mechanisms contributing to the emergence of slow oscillations in the basal ganglia after dopamine cell lesion in the anesthetized preparation, they are compatible with 1) increased oscillatory activity in the GP facilitated by an effect of dopamine loss on striatal 'filtering' of slow components of oscillatory cortical input, 2) increased oscillatory activity in STN spike trains supported by convergent antiphase inhibitory and excitatory oscillatory input from GP and cortex, respectively, and 3) increased oscillatory activity in SNpr spike trains organized by convergent antiphase inhibitory and excitatory oscillatory input from GP and STN, respectively. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errorsmaybe discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2012 May 17. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript KeywordsParkinson's disease; subthalamic nucleus; substantia nigra; globus pallidus; striatum; bursting; local field potentials Dopa...

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“…The change in SNr Glu levels after dopaminergic denervation may be attributable to an effect restricted to the STN or related structures. Many studies have reported direct dopaminergic innervation of the STN (Brown et al, 1979;Meibach and Katzman, 1979;Campbell et al, 1985;Hassani et al, 1997;Smith et al, 1998), which may control STN neuron activity directly or via presynaptic modulation of neurotransmitter release (Kreiss et al, 1997;Ni et al, 2001;Shen et al, 2003;Cragg et al, 2004). The level of GABA in the SNr also increased in hemiparkinsonian rats.…”

Section: Changes In Basal Glu and Gaba Level Induced By Snc Lesioningmentioning

confidence: 96%

Pallidal Origin of GABA Release within the Substantia Nigra Pars Reticulata during High-Frequency Stimulation of the Subthalamic Nucleus

Windels

Carcenac²,

Poupard³

et al. 2005

J. Neurosci.

119

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High-frequency stimulation of the subthalamic nucleus (HFS-STN) is an effective treatment for alleviating the motor symptoms of parkinsonian patients. However, the neurochemical basis of its effects remains unknown. We showed previously that 1 h of HFS-STN in normal rats increases extracellular glutamate (Glu) level in the output nuclei of the STN, the globus pallidus (GP), and the substantia nigra pars reticulata (SNr), consistent with an increase in the activity of STN neurons. HFS-STN also increases GABA levels in the SNr, but the origin of this increase is unclear. We investigated the effectiveness of HFS-STN for improving Parkinson's disease symptoms, using intracerebral microdialysis to determine the extracellular Glu and GABA levels of the GP and SNr in response to HFS-STN in anesthetized hemiparkinsonian rats [6-hydroxydopamine lesion of the substantia nigra pars compacta (SNc)]. Basal levels of Glu and GABA in the GP and SNr were significantly higher in hemiparkinsonian than in intact rats. HFS-STN did not affect extracellular Glu level in the SNr of hemiparkinsonian rats but doubled the level of GABA. Ibotenic acid lesion of the GP abolished the increase in GABA levels in the SNr induced by HFS-STN in SNc-lesioned rats. These results provide neurochemical confirmation of the hyperactivity of the STN after dopaminergic denervation and suggest that the therapeutic effects of HFS-STN may result partly from the stimulation of pallidonigral fibers, thereby revealing a potential role for pallidal GABA in the inhibition of basal ganglial output structures during HFS-STN.

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The Response of Subthalamic Nucleus Neurons to Dopamine Receptor Stimulation in a Rodent Model of Parkinson’s Disease

Cited by 171 publications

References 64 publications

Dopamine deficiency increases synchronized activity in the rat subthalamic nucleus

Dopamine deficiency increases synchronized activity in the rat subthalamic nucleus

Phase relationships support a role for coordinated activity in the indirect pathway in organizing slow oscillations in basal ganglia output after loss of dopamine

Pallidal Origin of GABA Release within the Substantia Nigra Pars Reticulata during High-Frequency Stimulation of the Subthalamic Nucleus

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