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Neuron. 2016 Feb 17;89(4):734-40. doi: 10.1016/j.neuron.2015.12.038. Epub 2016 Jan 28.

Pathway-Specific Remodeling of Thalamostriatal Synapses in Parkinsonian Mice.

Author information

1
Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA; Gladstone Institutes, San Francisco, CA 94158, USA.
2
Gladstone Institutes, San Francisco, CA 94158, USA.
3
Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA; Gladstone Institutes, San Francisco, CA 94158, USA; Departments of Physiology and Neurology, University of California San Francisco, CA 94158, USA. Electronic address: akreitzer@gladstone.ucsf.edu.

Abstract

Movement suppression in Parkinson's disease (PD) is thought to arise from increased efficacy of the indirect pathway basal ganglia circuit, relative to the direct pathway. However, the underlying pathophysiological mechanisms remain elusive. To examine whether changes in the strength of synaptic inputs to these circuits contribute to this imbalance, we obtained paired whole-cell recordings from striatal direct- and indirect-pathway medium spiny neurons (dMSNs and iMSNs) and optically stimulated inputs from sensorimotor cortex or intralaminar thalamus in brain slices from control and dopamine-depleted mice. We found that dopamine depletion selectively decreased synaptic strength at thalamic inputs to dMSNs, suggesting that thalamus drives asymmetric activation of basal ganglia circuitry underlying parkinsonian motor impairments. Consistent with this hypothesis, in vivo chemogenetic and optogenetic inhibition of thalamostriatal terminals reversed motor deficits in dopamine-depleted mice. These results implicate thalamostriatal projections in the pathophysiology of PD and support interventions targeting thalamus as a potential therapeutic strategy.

PMID:
26833136
PMCID:
PMC4760843
DOI:
10.1016/j.neuron.2015.12.038
[Indexed for MEDLINE]
Free PMC Article

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