Skip to main content
SpringerLink
Log in

The Contribution of the External Globus Pallidus to Basal Ganglia Circuit Oscillatory Activity in an Experimental Model of Parkinson’s Disease

  • Published:
Neuroscience and Behavioral Physiology Aims and scope Submit manuscript

Aberrant synchronous β oscillations in motor neural networks in dopamine (DA) deficiency are associated with motor impairments in Parkinson’s disease (PD). The sources and mechanisms of their development are unclear. The aim of the present work was to determine the role of the external part of the globus pallidus (GPe) and the central component of the basal ganglia (BG) in generating and transmitting β oscillations in motor neural networks in a model of PD in rats. Analysis of local field potentials (LFP) in traces from the motor area of the cerebral cortex (MCx) and BG nuclei revealed the greatest β-oscillation (30–36 Hz) power and coherence levels in the MCx and reticular part of the substantia nigra (SNr) of hemispheres with DA deficit, while their levels in the dorsal segment of the lateral striatum (dStr) and GPe and coherence with the MCx and Snr were significantly lower. Apart from β oscillations, increases in the coherence of γ oscillations in the range 50–56 Hz were observed exclusively in the dStr and GPe in DA deficiency and their transient appearance in control rats coincided with the onset of difficulties with walking. Stimulation of DA receptors with levodopa decreased synchronization in the neural networks of hemispheres with DA deficiency and restored normal locomotion. Differences between the two types of activity (β and γ oscillations) in traces from the GPe in DA deficiency provide evidence of the complexity of the organization of motor neural networks which in normal conditions control different aspects of locomotion.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abdi, A., Mallet, N., Mohamed, F. Y., et al., “Prototypic and arkypallidal neurons in the dopamine-intact external globus pallidus,” J. Neurosci., 17, 6667–6688 (2015).

    Article  Google Scholar 

  • Abecassis, Z. A., Berceau, B. L., Win, P. H., et al., “Npas1+–Nkx2.1+ neurons are an integral part of the cortico-pallido-cortical loop,” J. Neurosci., 4, 743–768 (2020).

    Article  Google Scholar 

  • Abrahao, K. P. and Lovinger, D. M., “Classification of GABAergic neuron subtypes from the globus pallidus using wild-type and transgenic mice,” J. Physiol., 596, 4219–4235 (2018).

    Article  Google Scholar 

  • Albin, R. L., Young, A. B., and Penney, J. B., “The functional anatomy of basal ganglia disorders,” Trends Neurosci., 12, 366–375 (1989).

    Article  Google Scholar 

  • Avila, I., Parr-Brownlie, L. C., Brazhnik, et al., “Beta frequency synchronization in basal ganglia output during rest and walk in a hemiparkinsonian rat,” Exp. Neurol., 2, 307–319 (2010).

    Article  Google Scholar 

  • Baaske, M. K., Kormann, E., Holt, A. B., et al., “Parkinson’s disease uncovers an underlying sensitivity of subthalamic nucleus neurons to beta-frequency cortical input in vivo,” Neurobiol. Dis., 146, 105– 119 (2020).

    Article  Google Scholar 

  • Belluscio, V., Stuart, S., Bergamini, E., et al., “The association between prefrontal cortex activity and turning behavior in people with and without freezing of gait,” Neuroscience, 416, 168–176 (2019).

    Article  Google Scholar 

  • Berke, J. D., “Fast oscillations in cortical-striatal networks switch frequency following rewarding events and stimulant drugs,” Eur. J. Neurosci., 30, 848–859 (2009).

    Article  Google Scholar 

  • Bevan, M. D., Magill, P. J., Terman, D., et al., “Review. Move to the rhythm: oscillations in the subthalamic nucleus-external globus pallidus network,” Trends Neurosci., 10, 525–531 (2002).

    Article  Google Scholar 

  • Brazhnik, E., Cruz, A. V., Avila, I., et al., “State-dependent spike and local fi eld synchronization between motor cortex and substantia nigra in hemiparkinsonian rats,” J. Neurosci., 32, 7869–7880 (2012).

    Article  Google Scholar 

  • Brazhnik, E., McCoy, A. J., Novikov, N., et al., “Ventral medial thalamic nucleus promotes synchronization of increased high beta oscillatory activity in the basal ganglia-thalamocortical Network of the hemiparkinsonian rat,” J. Neurosci., 36, 4196–4208 (2016).

    Article  Google Scholar 

  • Brittain, J. S., Sharott, A., and Brown, P., “The highs and lows of beta activity in cortico-basal ganglia loops,” Eur. J. Neurosci., 39, 1951– 1959 (2014).

    Article  Google Scholar 

  • Brown, P., “Bad oscillations in Parkinson’s disease,” J. Neural. Transm., 70, 27–30 (2006).

    Google Scholar 

  • Cacciola, A., Milardi, D., Bertino, S., et al., “Structural connectivity-based topography of the human globus pallidus: Implications for therapeutic targeting in movement disorders,” Mov. Disord., 7, 987–996 (2019).

    Article  Google Scholar 

  • Cardin, J. A., Carlén, M., Meletis, K., et al., “Driving fast-spiking cells induces gamma rhythm and controls sensory responses,” Nature, 459, 663–667 (2009).

    Article  Google Scholar 

  • Chen, M. C., Ferrari, L., Sacchet, M. D., et al., “Identification of a direct GABAergic pallidocortical pathway in rodents,” Eur. J. Neurosci. Mov. Disord., 30, 293–295 (2015).

    Google Scholar 

  • Choi, K., Holly, E., Davatolhagh, M. F., et al., “Integrated anatomical and physiological mapping of striatal afferent projections,” Eur. J. Neurosci., 49, No. 5, 623–636 (2019).

    Article  Google Scholar 

  • Chuhma, N., “Functional connectome analysis of the striatum with optogenetics,” Adv. Exp. Med. Biol., 1293, 417–428 (2021).

    Article  Google Scholar 

  • Corbit, V. L., Whalen, T. C., Zitelli, K. T., et al., “Pallidostriatal projections promote β oscillations in a dopamine-depleted biophysical network model,” J. Neurosci., 2, 5556–5571 (2016).

    Article  Google Scholar 

  • de la Crompe, B., Aristieta, A., Leblois, A., et al., “The globus pallidus orchestrates abnormal network dynamics in a model of Parkinsonism,” Nat. Commun., 11, 1570–1584 (2020).

    Article  Google Scholar 

  • Dejean, C. A., Le Moine, C., Bioulac, B., et al., “Evolution of the dynamic properties of the cortex-basal ganglia network after dopaminergic depletion in rats,” Neurobiol. Dis., 2, 402–413 (2012).

    Article  Google Scholar 

  • Delaville, C., McCoy, A. J., Gerber, C. M., et al., “Subthalamic nucleus activity in the awake hemiparkinsonian rat: relationships with motor and cognitive networks,” J. Neurosci., 17, 6918–6930 (2015).

    Article  Google Scholar 

  • Dodson, P. D., Larvin, J. T., Duffell, J. M., et al., “Distinct developmental origins manifest in the specialized encoding of movement by adult neurons of the external globus pallidus,” Neuron, 86, 501–513 (2015).

    Article  Google Scholar 

  • Eid, L. and Parent, M., “Morphological evidence for dopamine interactions with pallidal neurons in primates,” Front. Neuroanat., 9, 1–14 (2015).

    Google Scholar 

  • Gauthier, J., Parent, M., Levesque, M., and Parent, A., “The axonal arborization of single nigrostriatal neurons in rats,” Brain Res., 834, 228– 232 (1999).

    Article  Google Scholar 

  • Gittis, A. H., Berke, J. D., Bevan, M. D., et al., “New roles for the external globus pallidus in basal ganglia circuits and behavior,” J. Neurosci., 34, 15178–15183 (2014).

    Article  Google Scholar 

  • Glajch, K. E., Kelver, D. A., Hegeman, D. J., et al., “Npas1+ pallidal neurons target striatal projection neurons,” J. Neurosci., 36, 5472–5488 (2016).

    Article  Google Scholar 

  • Grewal, S. S., Holanda, V. M., and Middlebrook, E. Y., “Corticopallidal connectome of the globus pallidus externus in humans: An exploratory study of structural connectivity using probabilistic diffusion tractography,” Am. J. Neuroradiology, 11, 2120–2125 (2018).

    Article  Google Scholar 

  • Hegeman, D. J., Hong, E. S., Hernández, V. M., and Chan, C., “The external globus pallidus: progress and perspectives,” Eur. J. Neurosci., 10, 1239–1265 (2016).

    Article  Google Scholar 

  • Hernández, V. M., Hegeman, D. J., Cui, Q., et al., “Parvalbumin+ neurons and Npas1+ neurons are distinct neuron classes in the mouse external globus pallidus,” J. Neurosci., 35, 11,830–11,847 (2015).

  • Karube, F., Takahashi, S., Kobayashi, K., and Fujiyama, F., “Motor cortex can directly drive the globus pallidus neurons in a projection neuron type-dependent manner in the rat,” eLife, 8, e49511 (2019).

    Article  Google Scholar 

  • Ketzef, M. and Silberberg, G., “Differential synaptic input to external globus pallidus neuronal subpopulations in vivo,” Neuron, 109, No. 3, 516–529 (2021).

    Article  Google Scholar 

  • Kita, H., Globus pallidus external segment,” Prog. Brain Res., 160, 111–133 (2007).

    Article  Google Scholar 

  • Koelman, L. A. and Lowery, M. M., “Beta-band resonance and intrinsic oscillations in a biophysically detailed model of the subthalamic nucleus- globus pallidus network,” Front. Comput. Neurosci., 13, 1–24 (2019).

    Article  Google Scholar 

  • Lemaire, N., Hernández, L. F., Hu, D., et al., “Effects of dopamine depletion on LFP oscillations in striatum are task- and learning-dependent and selectively reversed by L-DOPA,” Proc. Natl. Acad. Sci. USA, 109, 18,126–18,131 (2012).

    Article  Google Scholar 

  • Litvak, V., Jha, A., Eusebio, A., et al., “Resting oscillatory cortico-subthalamic connectivity in patients with Parkinson’s disease,” Brain, 134, 359–374 (2011).

    Article  Google Scholar 

  • Maidan, I., Bernad-Elazari, H., Gazit, E., et al., “Changes in oxygenated hemoglobin link freezing of gait to frontal activation in patients with Parkinson disease: an fNIRS study of transient motor-cognitive failures,” J. Neurol., 4, 899–908 (2015).

    Article  Google Scholar 

  • Mallet, N., Delgado, L., Chazalon, M., et al., “Cellular and synaptic dysfunctions in parkinson’s disease: Stepping out of the striatum,” Cells, 9, 1005 (2019).

    Article  Google Scholar 

  • Mallet, N., Micklem, B. R., Henny, P., et al., “Dichotomous organization of the external globus pallidus,” Neuron, 74, 1075–1086 (2012).

    Article  Google Scholar 

  • Mallet, N., Pogosyan, A., Marton, L. F., et al., “Parkinsonian beta oscillations in the external globus pallidus and their relationship with subthalamic nucleus activity,” J. Neurosci., 52, 14,245–14,258 (2008).

    Article  Google Scholar 

  • Mallet, N., Schmidt, R., Leventhal, D., et al., “Arkypallidal cells send a stop signal to striatum,” Neuron, 89, 308–316 (2016).

    Article  Google Scholar 

  • Mastro, K. J., Bouchard, R. S., Holt, H. A., and Gittis, A. H., “Transgenic mouse lines subdivide external segment of the globus pallidus (GPe) neurons and reveal distinct GPe output pathways,” J. Neurosci., 34, 2087–2099 (2014).

    Article  Google Scholar 

  • Mastro, K. J., Zitelli, K. T., Willard, A. M., et al., “Cell-specifi c pallidal intervention induces long-lasting motor recovery in dopamine-depleted mice,” Nat. Neurosci., 20, 815–823 (2017).

    Article  Google Scholar 

  • McCarthy, M. M., Moore-Kochlacs, C., Gu, X., et al., “Striatal origin of the pathologic beta oscillations in Parkinson’s disease,” Proc. Natl. Acad. Sci. USA, 108, 11,620–11,625 (2011).

    Article  Google Scholar 

  • McGregor, M. M., McKinsey, G. L., Girasole, A. E., et al., “Functionally distinct connectivity of developmentally targeted striosome neurons,” Cell Rep., 29, No. 6, 1419–1428 (2019).

    Article  Google Scholar 

  • Nambu, A., Tokuno, H., and Takada, M., “Functional signifi cance of the cortico-subthalamo-pallidal ‘hyperdirect’ pathway,” Neurosci. Res., 2,111–117 (2002).

    Article  Google Scholar 

  • Neumann, W. J., Degen, K., Schneider, G. H., et al., “Subthalamic synchronized oscillatory activity correlates with motor impairment in patients with Parkinson’s disease,” Mov. Disord., 31,1748–1751 (2016).

    Article  Google Scholar 

  • Nevado-Holgado, A. J., Mallet, N., Magill, P. J., and Bogacz, R., “Effective connectivity of the subthalamic nucleus–globus pallidus network during Parkinsonian oscillations,” J. Physiol., 592, No. 7, 1429– 1455 (2014).

    Article  Google Scholar 

  • Pamukcu, A., Cui, Q., Xenias, H. S., et al., “Parvalbumin (+) and Npas1(+) pallidal neurons have distinct circuit topology and function,” J. Neurosci., 40, 7855–7876 (2020).

    Article  Google Scholar 

  • Parent, A. and Hazrati, L. N., “Functional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamo-cortical loop,” Brain Res. Brain Res. Rev., 1, 91–127 (1995).

    Article  Google Scholar 

  • Plenz, D. and Kital, S. T., “A basal ganglia pacemaker formed by the subthalamic nucleus and external globus pallidus,” Nature, No. 6745, 677–682 (1999).

    Article  Google Scholar 

  • Pogosyan, A., Yoshida, F., Chen, C. C., et al., “Parkinsonian impairment correlates with spatially extensive subthalamic oscillatory synchronization,” Neuroscience, 171, No. 1, 245–257 (2010).

    Article  Google Scholar 

  • Polyakova, Z., Chiken, S., Hatanaka, N., and Nambu, A., “Cortical control of subthalamic neuronal activity through the hyperdirect and indirect pathways in monkeys,” J. Neurosci., 39, 7451–7463 (2020).

    Article  Google Scholar 

  • Rodriguez-Sabate, C., Morales, I., Monton, F., and Rodriguez, M., “The influence of Parkinson’s disease on the functional connectivity of the motor loop of human basal ganglia,” Parkinsonism Relat. Disord., 63, 100–105 (2019).

    Article  Google Scholar 

  • Saunders, A., Oldenburg, I. A., Berezovskii, V. K., et al., “A direct GABAergic output from the basal ganglia to frontal cortex,” Nature, 521, 85–89 (2015).

    Article  Google Scholar 

  • Sharott, A., Gulberti, A., Hamel, W., et al., “Spatio-temporal dynamics of cortical drive to human subthalamic nucleus neurons in Parkinson’s disease,” Neurobiol. Dis., 112, 49–62 (2018).

    Article  Google Scholar 

  • Sharott, A., Gulberti, A., Zittel, S., et al., “Activity parameters of subthalamic nucleus neurons selectively predict motor symptom severity in Parkinson’s disease,” J. Neurosci., 34, 6273–6285 (2014).

    Article  Google Scholar 

  • Sharott, A., Magill, P. J., Harnack, D., et al., “Dopamine depletion increases the power and coherence of beta-oscillations in the cerebral cortex and subthalamic nucleus of the awake rat,” Eur. J. Neurosci., 5, 1413–1422 (2005).

    Article  Google Scholar 

  • Singh, A., “Oscillatory activity in the cortico-basal ganglia-thalamic neural circuits in Parkinson’s disease,” Eur. J. Neurosci., 8, 2869–2878 (2018).

    Article  Google Scholar 

  • Smith, J. B., Klug, J. R., Ross, D. L., et al., “Genetic-based dissection unveils the inputs and outputs of striatal patch and matrix compartments,” Neuron, 91, No. 5, 1069–1084. (2016).

    Article  Google Scholar 

  • Smith, Y. and Villalba, R., “Striatal and extrastriatal dopamine in the basal ganglia: an overview of its anatomical organization in normal and Parkinsonian brains,” Mov. Disord., 3, S534–547 (2008).

    Article  Google Scholar 

  • Tachibana, Y., Iwamuro, H., Kita, H., et al., “Subthalamo-pallidal interactions underlying parkinsonian neuronal oscillations in the primate basal ganglia,” Eur. J. Neurosci., 34, 1470–1484 (2011).

    Article  Google Scholar 

  • Weinberger, M., Hutchison, W. D., and Dostrovsky, J. O., “Pathological subthalamic nucleus oscillations in PD: can they be the cause of bradykinesia and akinesia?” Exp. Neurol., 1, 58–61 (2009).

    Article  Google Scholar 

  • West, T. O., Berthouze, L., Halliday, D. M., et al., “Propagation of beta/ gamma rhythms in the cortico-basal ganglia circuits of the parkinsonian rat,” J. Neurophysiol., 5, 1608–1628 (2018).

    Article  Google Scholar 

  • Yasukawa, T., Kita, T., Xue, Y., and Kita, H., “Rat intralaminar thalamic nuclei projections to the globus pallidus: a biotinylated dextran amine anterograde tracing study,” J. Comp. Neurol., 2, 153–167 (2004).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Theoretical and Experimental Biophysics, Pushchino, Russia

    M. V. Morozova, E. S. Brazhnik, I. E. Mysin & N. I. Novikov

  2. Belozerskii Research Institute of Physicochemical Biology, Lomonosov Moscow State University, Moscow, Russia

    L. B. Popova

Authors
  1. M. V. Morozova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. S. Brazhnik
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I. E. Mysin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. B. Popova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N. I. Novikov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N. I. Novikov.

Additional information

Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 72, No. 1, pp. 100–116, January–February, 2022.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Morozova, M.V., Brazhnik, E.S., Mysin, I.E. et al. The Contribution of the External Globus Pallidus to Basal Ganglia Circuit Oscillatory Activity in an Experimental Model of Parkinson’s Disease. Neurosci Behav Physi 52, 1061–1072 (2022). https://doi.org/10.1007/s11055-022-01334-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11055-022-01334-z

Keywords

Search

Navigation