Oscillatory Activity and Synchronization in the Basal Ganglia Network in Rodent Models of Parkinson’s Disease
The efficacy of deep brain stimulation (DBS) in the subthalamic nucleus (STN) in Parkinson’s disease (PD) has focused attention on the role of STN firing patterns in PD symptomatology. Oscillatory activity in the beta frequency range is of special interest as local field potential (LFP) recordings in the STN in bradykinetic PD patients during DBS electrode placement show prominent activity in this frequency range. As increased synchronization between the globus pallidus pars externus (GP) and STN has been implicated in the emergence of oscillatory activity in the STN, the effect of dopamine loss and increased dopamine stimulation on beta range activity in paired GP-STN single unit and LFP recordings was examined in intact or nigrostriatally lesioned, locally anesthetized, and immobilized rats. Spike-triggered waveform averages (STWAs) show that GP spiking becomes significantly more synchronized with STN LFP oscillations in the beta range after dopamine cell lesion. Coherences between GP spiking and STN LFP and between STN spiking and STN LFP are increased after dopamine cell lesion. A desynchronizing effect of increased dopamine receptor stimulation with apomorphine on GP-STN relationships in both intact and lesioned rats is observed. Results support a role for increased synchronization between STN and GP in the emergence of beta range activity in the STN and a greater impact of GP on STN activity after decreased dopamine receptor stimulation.
KeywordsDeep Brain Stimulation Spike Train Local Field Potential Oscillatory Activity Beta Frequency
The Intramural Research Program of the NINDS, NIH supported this research.
- Avila I, Parr-Brownlie LC, Bergstrom DA, Gonzales KK, Poloskey SL, Castaneda E and Walters JR (2007) Firing rate and local field potential changes in a basal ganglia output nucleus during walking and rest in the hemiparkinsonian rat. Soc Neurosci Abstr 2007 Online Program No. 622.8.Google Scholar
- Gatev P and Wichmann T (2009) Interactions between cortical rhythms and spiking activity of single basal ganglia neurons in the normal and parkinsonian state. Cereb Cortex 19: 1330–1344.Google Scholar
- Ghiglieri V, Soucy AL, Itoga CA, Bergstrom DA and Walters JR (2003) Dopamine D2 receptor blockade affects relationships between single unit neuronal activity and local field potential power in the globus pallidus of head-restrained and freely moving rats. Soc Neurosci Abstr 2003 Online Program No. 273.4.Google Scholar
- Heimer G, Rivlin-Etzion M, Bar-Gad I, Goldberg JA, Haber SN and Bergman H (2006) Dopamine replacement therapy does not restore the full spectrum of normal pallidal activity in the 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine primate model of parkinsonism. J Neurosci 26: 8101–8114.CrossRefPubMedGoogle Scholar
- Kelland MD, Soltis RP, Anderson LA, Bergstrom DA and Walters JR (1995) In vivo characterization of two cell types in the rat globus pallidus which have opposite responses to dopamine receptor stimulation: comparison of electrophysiological properties and responses to apomorphine, dizocilpine, and ketamine anesthesia. Synapse 20: 338–350.CrossRefPubMedGoogle Scholar
- Parr-Brownlie LC, Poloskey SL, Flanagan KK, Eisenhofer G, Bergstrom DA and Walters JR (2007) Dopamine lesion-induced changes in subthalamic nucleus activity are not associated with alterations in firing rate or pattern in layer V neurons of the anterior cingulate cortex in anesthetized rats. Eur J Neurosci 26: 1925–1939.CrossRefPubMedGoogle Scholar
- Priori A, Foffani G, Pesenti A, Bianchi A, Chiesa V, Baselli G, Caputo E, Tamma F, Rampini P, Egidi M, Locatelli M, Barbieri S and Scarlato G (2002) Movement-related modulation of neural activity in human basal ganglia and its L-DOPA dependency: recordings from deep brain stimulation electrodes in patients with Parkinson’s disease. Neurol Sci 23: S101-S102.CrossRefPubMedGoogle Scholar
- Raz A, Frechter-Mazar V, Feingold A, Abeles M, Vaadia E and Bergman H (2001) Activity of pallidal and striatal tonically active neurons is correlated in MPTP-treated monkeys but not in normal monkeys. J Neurosci 21 (RC128): 1–5.Google Scholar
- Tierney PL, Bergstrom DA, Ruskin DN and Walters JR (2002) Correlation between multisecond oscillations in firing rate in basal ganglia neurons: modulation by dopamine receptor stimulation and association with hippocampal theta rhythm. Soc Neurosci Abstr 2002 Online Program No. 765.3.Google Scholar
- Tierney PL, Bergstrom DA, Soucy AL, Itoga CA, Allers KA, Ruskin DN and Walters JR (2003) Single unit activity and local field potentials in paired recordings from subthalamic nucleus and globus pallidus neurons in awake rats: effect of alterations in dopamine receptor stimulation. Soc Neurosci Abstr 2003 Online Program No. 273.5.Google Scholar
- Vila M, Perier C, Feger J, Yelnik J, Faucheux B, Ruberg M, Raisman-Vozari R, Agid Y and Hirsch EC (2000) Evolution of changes in neuronal activity in the subthalamic nucleus of rats with unilateral lesion of the substantia nigra assessed by metabolic and electrophysiological measurements. Eur J Neurosci 12: 337–344.CrossRefPubMedGoogle Scholar
- Walters JR, Hu D, Itoga CA, Parr-Brownlie LC and Bergstrom DA (2005) Do local field potentials reflect synchronized spiking activity of neuronal populations in the basal ganglia? Studies in a rodent model of Parkinson’s disease. In: Bolam JP, Magill PJ, Ingham C (eds) The Basal Ganglia VIII. Springer, New York, pp 37–46.CrossRefGoogle Scholar