Journal
JOURNAL OF NEUROSCIENCE
Volume 37, Issue 41, Pages 9977-9998Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0658-17.2017
Keywords
basal ganglia; dopamine; electrophysiology; oscillations; Parkinson's disease; striatum
Categories
Funding
- UK Medical Research Council (MRC) [MC_UU_12024/1, UU138197109, MC_UU_12020/5, MC_UU_12024/2]
- Parkinson's UK [G-0806]
- Wellcome Trust [101821]
- Marie Curie European Re-integration Grant (SNAP-PD) - European Union
- MRC
- Human Frontier Science Program [LT000396/2009-L]
- Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT) [21700380, 15H01663]
- MRC [MC_U138197109, MC_UU_12020/5, MC_UU_12024/1, MC_UU_12024/2] Funding Source: UKRI
- Wellcome Trust [101821/Z/13/Z] Funding Source: Wellcome Trust
- Medical Research Council [MC_U138197109, 1310799, MC_UU_12024/1, MC_UU_12020/5, MC_UU_12024/2] Funding Source: researchfish
- Parkinson's UK [G-0806, J-1403, J-0901] Funding Source: researchfish
- Wellcome Trust [101821/Z/13/Z] Funding Source: researchfish
- Grants-in-Aid for Scientific Research [15H01663, 21700380] Funding Source: KAKEN
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Classical schemes of basal ganglia organization posit that parkinsonian movement difficulties presenting after striatal dopamine depletion stem from the disproportionate firing rates of spiny projection neurons (SPNs) therein. There remains, however, a pressing need to elucidate striatal SPN firing in the context of the synchronized network oscillations that are abnormally exaggerated in cortical-basal ganglia circuits in parkinsonism. To address this, we recorded unit activities in the dorsal striatum of dopamine-intact and dopamine-depleted rats during two brain states, respectively defined by cortical slow-wave activity (SWA) and activation. Dopamine depletion escalated striatal net output but had contrasting effects on direct pathway SPNs (dSPNs) and indirect pathway SPNs (iSPNs); their firing rates became imbalanced, and they disparately engaged in network oscillations. Disturbed striatal activity dynamics relating to the slow (similar to 1 Hz) oscillations prevalent during SWA partly generalized to the exaggerated beta-frequency (15-30 Hz) oscillations arising during cortical activation. In both cases, SPNs exhibited higher incidences of phase-locked firing to ongoing cortical oscillations, andSPN ensembles showed higher levels of rhythmic correlated firing, after dopamine depletion. Importantly, in dopamine-depleted striatum, a widespread population of iSPNs, which often displayed excessive firing rates and aberrant phase-locked firing to cortical beta oscillations, preferentially and excessively synchronized their firing at beta frequencies. Conversely, dSPNs were neither hyperactive nor synchronized to a large extent during cortical activation. These data collectively demonstrate a cell type-selective entrainment of SPN firing to parkinsonian beta oscillations. We conclude that a population of overactive, excessively synchronized iSPNs could orchestrate these pathological rhythms in basal ganglia circuits.
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