Localization and pharmacological modulation of GABA-B receptors in the globus pallidus of parkinsonian monkeys

Galván, Adriana; Hu, Xing; Smith, Yoland; Wichmann, Thomas

doi:10.1016/j.expneurol.2011.03.010

Cited by 30 publications

(18 citation statements)

References 55 publications

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“…As expected, postmortem TH staining revealed a substantial loss of dopamine in striatum and SNc in all three animals (Supplementary Fig. 2), similar to that reported in previous papers (Galvan et al, 2011). …”

Section: Resultssupporting

confidence: 90%

Relationship between oscillatory activity in the cortico-basal ganglia network and parkinsonism in MPTP-treated monkeys

Devergnas

Pittard

Bliwise

et al. 2014

Neurobiology of Disease

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Parkinsonism is associated with changes in oscillatory activity patterns and increased synchronization of neurons in the basal ganglia and cortex in patients and animal models of Parkinson's disease, but the relationship between these changes and the severity of parkinsonian signs remains unclear. We examined this relationship by studying changes in local field potentials (LFPs) in the internal pallidal segment (GPi) and the subthalamic nucleus (STN), and in encephalographic signals (EEG) from the primarymotor cortex (M1) in Rhesus monkeys which were rendered progressively parkinsonian by repeated systemic injections of small doses of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Observations during wakefulness and sleep (defined by EEG and video records) were analyzed separately. The severity of parkinsonism correlated with increases in spectral power at frequencies below 15.5 Hz in M1 and GPi and reductions in spectral power at frequencies above 15.6 Hz with little change in STN. The severity of parkinsonism also correlated with increases in the coherence betweenM1 EEG and basal ganglia LFPs in the low frequency band. Levodopa treatment reduced low-frequency activity and increased high-frequency activity in all three areas, but did not affect coherence. The state of arousal also affected LFP and EEG signals in all three structures, particularly in the STN. These results suggest that parkinsonism-associated changes in alpha and low-beta band oscillatory activity can be detected early in the parkinsonian state in M1 and GPi. Interestingly, oscillations detectable in STN LFP signals (including oscillations in the beta-band) do not appear to correlate strongly with the severity of mild-to-moderate parkinsonism in these animals. Levodopa-induced changes in oscillatoryM1 EEG and basal ganglia LFP patterns do not necessarily represent a normalization of abnormalities caused by dopamine depletion.

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Section: Resultssupporting

confidence: 90%

Relationship between oscillatory activity in the cortico-basal ganglia network and parkinsonism in MPTP-treated monkeys

Devergnas

Pittard

Bliwise

et al. 2014

Neurobiology of Disease

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“…Other factors, such as the level of membrane depolarization of CM/Pf neurons compared with VA may also account for their differential propensity in developing LTS. If such is the case, these observations add further evidence to the concept put forward in our previous studies that CM/Pf neurons are a unique subpopulation of thalamic neurons endowed with anatomical and functional properties distinct from most other thalamic neurons (Galvan et al, 2011; Smith et al, 2004, 2014). …”

Section: Discussionsupporting

confidence: 82%

“…; Sigma, St. Louis, MO; cumulative doses: 2.8 – 8.8 mg/kg) once per week, until they reached a state of stable moderate parkinsonism. The degree and stability of the MPTP-induced motor disability was assessed, as described in many previous studies from our laboratory (Galvan et al, 2011; 2014; Masilamoni et al, 2011; Bogenpohl et al, 2013; Villalba et al, 2014; Devergnas et al, 2014, Mathai et al, 2015). Briefly, animals were evaluated weekly in an observation cage that was equipped with infrared beams, allowing us to measure their body movements as infrared beam break events.…”

Section: Methodsmentioning

confidence: 99%

“…Using Imagescope image viewing software (Aperio) and the NIH Image J software (Schneider et al, 2012), we quantified the intensity of Cav3.1 immunostaining from digital 0.4x magnification images of immunostained tissue slides containing the motor thalamus in a manner similar to that reported in our previous studies (Galvan et al, 2011). The images were converted into 16-bit grayscale format and inverted.…”

Section: Methodsmentioning

confidence: 99%

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Sub-synaptic localization of Cav3.1 T-type calcium channels in the thalamus of normal and parkinsonian monkeys

et al. 2016

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T-type calcium channels (Cav3) are key mediators of thalamic bursting activity, but also regulate single cells excitability, dendritic integration, synaptic strength and transmitter release. These functions are strongly influenced by the subcellular and subsynaptic localization of Cav3 channels along the somatodendritic domain of thalamic cells. In Parkinson’s disease, T-type calcium channels dysfunction in the basal ganglia-receiving thalamic nuclei likely contributes to pathological thalamic bursting activity. In this study, we analyzed the cellular, subcellular, and subsynaptic localization of the Cav3.1 channel in the ventral anterior (VA) and centromedian/parafascicular (CM/Pf) thalamic nuclei, the main thalamic targets of basal ganglia output, in normal and parkinsonian monkeys. All thalamic nuclei displayed strong Cav3.1 neuropil immunoreactivity, although the intensity of immunolabeling in CM/Pf was significantly lower than in VA. Ultrastructurally, 70–80% of the Cav3.1-immunoreactive structures were dendritic shafts. Using immunogold labeling, Cav3.1 was commonly found perisynaptic to asymmetric and symmetric axo-dendritic synapses, suggesting a role of Cav3.1 in regulating excitatory and inhibitory neurotransmission. Significant labeling was also found at non-synaptic sites along the plasma membrane of thalamic neurons. There was no difference in the overall pattern and intensity of immunostaining between normal and parkinsonian monkeys, suggesting that the increased rebound bursting in the parkinsonian state is not driven by changes in Cav3.1 expression. Thus, T-type calcium channels are located to subserve neuronal bursting, but also regulate glutamatergic and non-glutamatergic transmission along the whole somatodendritic domain of basal ganglia-receiving neurons of the primate thalamus.

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“…For neurons in which the injection had no effect on the firing rate, a 60-s data segment starting 140 s after the beginning of the injection was used for the analysis. Although "drug effects" can also be defined by other measures of neuronal activity (for instance, coefficients of variation), the use of these measures in previous studies from our laboratory (Galvan et al 2010(Galvan et al , 2011 did not provide evidence that this approach is superior to the more straightforward measurement of firing rate changes used in the present study.…”

Section: Electrophysiological Studiesmentioning

confidence: 62%

Extrastriatal D2-like receptors modulate basal ganglia pathways in normal and parkinsonian monkeys

Hadipour-Niktarash

Rommelfanger²,

Masilamoni³

et al. 2012

Journal of Neurophysiology

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According to traditional models of the basal ganglia-thalamocortical network of connections, dopamine exerts D2-like receptor (D2LR)-mediated effects through actions on striatal neurons that give rise to the "indirect" pathway, secondarily affecting the activity in the internal and external pallidal segments (GPi and GPe, respectively) and the substantia nigra pars reticulata (SNr). However, accumulating evidence from the rodent literature suggests that D2LR activation also directly influences synaptic transmission in these nuclei. To further examine this issue in primates, we combined in vivo electrophysiological recordings and local intracerebral microinjections of drugs with electron microscopic immunocytochemistry to study D2LR-mediated modulation of neuronal activities in GPe, GPi, and SNr of normal and MPTP-treated (parkinsonian) monkeys. D2LR activation with quinpirole increased firing in most GPe neurons, likely due to a reduction of striatopallidal GABAergic inputs. In contrast, local application of quinpirole reduced firing in GPi and SNr, possibly through D2LR-mediated effects on glutamatergic inputs. Injections of the D2LR antagonist sulpiride resulted in effects opposite to those of quinpirole in GPe and GPi. D2 receptor immunoreactivity was most prevalent in putative striatal-like GABAergic terminals and unmyelinated axons in GPe, GPi, and SNr, but a significant proportion of immunoreactive boutons also displayed ultrastructural features of glutamatergic terminals. Postsynaptic labeling was minimal in all nuclei. The D2LR-mediated effects and pattern of distribution of D2 receptor immunoreactivity were maintained in the parkinsonian state. Thus, in addition to their preferential effects on indirect pathway striatal neurons, extrastriatal D2LR activation in GPi and SNr also influences direct pathway elements in the primate basal ganglia under normal and parkinsonian conditions.

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Localization and pharmacological modulation of GABA-B receptors in the globus pallidus of parkinsonian monkeys

Cited by 30 publications

References 55 publications

Relationship between oscillatory activity in the cortico-basal ganglia network and parkinsonism in MPTP-treated monkeys

Relationship between oscillatory activity in the cortico-basal ganglia network and parkinsonism in MPTP-treated monkeys

Sub-synaptic localization of Cav3.1 T-type calcium channels in the thalamus of normal and parkinsonian monkeys

Extrastriatal D2-like receptors modulate basal ganglia pathways in normal and parkinsonian monkeys

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