Impaired glutamatergic projection from the motor cortex to the subthalamic nucleus in 6-hydroxydopamine-lesioned hemi-parkinsonian rats

Wang, Yanyan; Wang, Yong; Jiang, Hongmei; Liu, Junhua; Jia, Jinping; Wang, Ke; Zhao, Fei; Luo, Min‐Hua; Luo, Minmin; Wang, Xiaomin

doi:10.1016/j.expneurol.2017.11.006

Cited by 33 publications

(44 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This finding suggests that an altered ratio of GluN2D to GluN2B might be an important change associated with loss of dopaminergic neurons. Our current data are consistent with our previous study showing that the glutamatergic corticosubthalamic innervation of the STN was substantially reduced in MPTP-treated parkinsonian animals (Chu et al, 2017;Mathai et al, 2015;Pan et al, 2014;Sanders & Jaeger, 2016;Sanders, 2017;Wang et al, 2018), perhaps as a component of a more general glutamatergic disconnection of the basal ganglia (the cortico-and thalamostriatal innervation also fail in this disease; Villalba, Villalba & Smith, 2017). Thus, while blockade of glutamatergic transmission in the STN (e.g., through the use of GluN2D-selective antagonists) may have antiparkinsonian effects, these effects may be limited, given the apparent loss of GluN2D Stephen F. Traynelis http://orcid.org/0000-0002-3750-9615…”

Section: Discussionsupporting

confidence: 93%

NMDA receptor blockade ameliorates abnormalities of spike firing of subthalamic nucleus neurons in a parkinsonian nonhuman primate

Bhattacharya

Dunn

et al. 2018

J of Neuroscience Research

View full text Add to dashboard Cite

N-methyl-D-aspartate receptors (NMDARs) are ion channels comprising tetrameric assemblies of GluN1 and GluN2 receptor subunits that mediate excitatory neurotransmission in the central nervous system. Of the four different GluN2 subunits, the GluN2D subunit-containing NMDARs have been suggested as a target for antiparkinsonian therapy because of their expression pattern in some of the basal ganglia nuclei that show abnormal firing patterns in the parkinsonian state, specifically the subthalamic nucleus (STN). In this study, we demonstrate that blockade of NMDARs altered spike firing in the STN in a male nonhuman primate that had been rendered parkinsonian by treatment with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. In accompanying experiments in male rodents, we found that GluN2D-NMDAR expression in the STN was reduced in acutely or chronically dopamine-depleted animals. Taken together, our data suggest that blockade of NMDARs in the STN may be a viable antiparkinsonian strategy, but that the ultimate success of this approach may be complicated by parkinsonism-associated changes in NMDAR expression in the STN.

show abstract

Section: Discussionsupporting

confidence: 93%

NMDA receptor blockade ameliorates abnormalities of spike firing of subthalamic nucleus neurons in a parkinsonian nonhuman primate

Bhattacharya

Dunn

et al. 2018

J of Neuroscience Research

View full text Add to dashboard Cite

show abstract

“…Whereas therapeutic targets can be theoretically located at any point of this circuitry, motor symptoms have been partially ameliorated through traditional electrical (Li et al, 2012;de Hemptinne et al, 2015;Lofredi et al, 2018), chemogenetic (Alcacer et al, 2017;Chu et al, 2017), optogenetic (Gradinaru et al, 2009;Kravitz et al, 2010;Kim et al, 2017), and pharmacological (Guo et al, 2015) manipulations targeting primarily basal ganglia structures, such as striatum, STN, and pallidum. Although much progress has been made using these strategies, recent electrophysiology and functional imaging studies suggest that PD symptoms result from alterations in the cerebral cortex, and successful therapies, indeed, encompasses plastic changes in cortical neurons (Dejean et al, 2009;Gradinaru et al, 2009;Li et al, 2012;de Hemptinne et al, 2015;Guo et al, 2015;Chu et al, 2017;Wang et al, 2018). For example, DBS of STN reduced excessive beta phase locking of motor cortex neurons and improved cortical function of PD patients (de Hemptinne et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Optogenetic Stimulation of the M2 Cortex Reverts Motor Dysfunction in a Mouse Model of Parkinson's Disease

Magno¹,

Tenza-Ferrer²,

Collodetti³

et al. 2019

J. Neurosci.

View full text Add to dashboard Cite

Neuromodulation of deep brain structures (deep brain stimulation) is the current surgical procedure for treatment of Parkinson's disease (PD). Less studied is the stimulation of cortical motor areas to treat PD symptoms, although also known to alleviate motor disturbances in PD. We were able to show that optogenetic activation of secondary (M2) motor cortex improves motor functions in dopamine-depleted male mice. The stimulated M2 cortex harbors glutamatergic pyramidal neurons that project to subcortical structures, critically involved in motor control, and makes synaptic contacts with dopaminergic neurons. Strikingly, optogenetic activation of M2 neurons or axons into the dorsomedial striatum increases striatal levels of dopamine and evokes locomotor activity. We found that dopamine neurotransmission sensitizes the locomotor behavior elicited by activation of M2 neurons. Furthermore, combination of intranigral infusion of glutamatergic antagonists and circuit specific optogenetic stimulation revealed that behavioral response depended on the activity of M2 neurons projecting to SNc. Interestingly, repeated M2 stimulation combined with L-DOPA treatment produced an unanticipated improvement in working memory performance, which was absent in control mice under L-DOPA treatment only. Therefore, the M2-basal ganglia circuit is critical for the assembly of the motor and cognitive function, and this study demonstrates a therapeutic mechanism for cortical stimulation in PD that involves recruitment of long-range glutamatergic projection neurons.

show abstract

“…Figure 11 shows the averaged PSTH for each frequency with two prominent peaks corresponding to the early and late excitation in both groups. Interestingly, on average the peak is delayed in 6-OHDA lesioned animals, in line with a down-regulation of the hyper-direct pathway (Chu HY et al 2017;Wang YY et al 2018). Moreover, the mean z-score PSTH does not decrease to 0 in the 6-OHDA lesioned animals, an effect that was magnified as input frequency increased, supporting the idea of a decreased reciprocal inhibition from the GPe in the dopamine depleted state (Janssen MLF et al 2017).…”

Section: Figure 8 Example Responses Of Identified Stn-neurons To Cormentioning

confidence: 67%

Parkinson’s disease uncovers an underlying sensitivity of subthalamic nucleus neurons to beta-frequency cortical input

Baaske

Kormann

Holt

et al. 2019

Preprint

View full text Add to dashboard Cite

Abnormally sustained beta-frequency synchronisation between the motor cortex and subthalamic nucleus (STN) is associated with motor symptoms in Parkinson's disease (PD).It is currently unclear whether STN neurons have a preference for beta-frequency input (12-35Hz), rather than cortical input at other frequencies, and how such a preference would arise following dopamine depletion. To address this question, we combined analysis of cortical and STN recordings from awake PD patients undergoing deep brain stimulation surgery with recordings of identified STN neurons in anaesthetised rats. In PD patients, we demonstrate that a subset of STN neurons are strongly and selectively sensitive to fluctuations of cortical beta oscillations over time, linearly increasing their phase-locking strength with respect to full range of instantaneous amplitude. In rats, we probed the frequency response of STN neurons more precisely, by recording spikes evoked by short bursts of cortical stimulation with variable frequency (4-40Hz) and constant amplitude. In both healthy and dopaminedepleted animals, only beta-frequency stimulation selectively led to a progressive reduction in the variability of spike timing through the stimulation train. We hypothesize, that abnormal activation of the indirect pathway, via dopamine depletion and/or cortical stimulation, could trigger an underlying sensitivity of the STN microcircuit to beta-frequency input. Brown P. 2008. Highfrequency stimulation of the subthalamic nucleus suppresses oscillatory beta activity in patients with Parkinson's disease in parallel with improvement in motor performance. The Journal of neuroscience : the official journal of the Society for Neuroscience. 28:6165-6173. Kuhn AA, Trottenberg T, Kivi A, Kupsch A, Schneider GH, Brown P. 2005. The relationship between local field potential and neuronal discharge in the subthalamic nucleus of patients with Parkinson's disease. Experimental neurology. 194:212-220. Kühn AA, Tsui A, Aziz T, Ray N, Brucke C, Kupsch A, Schneider GH, Brown P. 2009. Pathological synchronisation in the subthalamic nucleus of patients with Parkinson's disease relates to both bradykinesia and rigidity. Exp Neurol. 215:380-387. Lachaux JP, Rodriguez E, Martinerie J, Varela FJ. 1999. Measuring phase synchrony in brain signals. Human brain mapping. 8:194-208. Lalo E, Thobois S, Sharott A, Polo G, Mertens P, Pogosyan A, Brown P. 2008. Patterns of bidirectional communication between cortex and basal ganglia during movement in patients with Parkinson disease. J Neurosci. 28:3008-3016. Levy R, Ashby P, Hutchison WD, Lang AE, Lozano AM, Dostrovsky JO. 2002. Dependence of subthalamic nucleus oscillations on movement and dopamine in Parkinson's disease. Brain : a journal of neurology. 125:1196-1209. Little S, Pogosyan A, Kuhn AA, Brown P. 2012. Beta band stability over time correlates with Parkinsonian rigidity and bradykinesia. Exp Neurol. 236:383-388.

show abstract

Impaired glutamatergic projection from the motor cortex to the subthalamic nucleus in 6-hydroxydopamine-lesioned hemi-parkinsonian rats

Cited by 33 publications

References 39 publications

NMDA receptor blockade ameliorates abnormalities of spike firing of subthalamic nucleus neurons in a parkinsonian nonhuman primate

NMDA receptor blockade ameliorates abnormalities of spike firing of subthalamic nucleus neurons in a parkinsonian nonhuman primate

Optogenetic Stimulation of the M2 Cortex Reverts Motor Dysfunction in a Mouse Model of Parkinson's Disease

Parkinson’s disease uncovers an underlying sensitivity of subthalamic nucleus neurons to beta-frequency cortical input

Contact Info

Product

Resources

About