Subthalamic, not striatal, activity correlates with basal ganglia downstream activity in normal and parkinsonian monkeys

Author:

Deffains Marc12ORCID,Iskhakova Liliya12,Katabi Shiran1,Haber Suzanne N3,Israel Zvi4,Bergman Hagai1ORCID

Affiliation:

1. Department of Medical Neurobiology, Institute of Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel

2. The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University, Jerusalem, Israel

3. Department of Pharmacology and Physiology, University of Rochester School of Medicine, Rochester, United States

4. Department of Neurosurgery, Hadassah University Hospital, Jerusalem, Israel

Abstract

The striatum and the subthalamic nucleus (STN) constitute the input stage of the basal ganglia (BG) network and together innervate BG downstream structures using GABA and glutamate, respectively. Comparison of the neuronal activity in BG input and downstream structures reveals that subthalamic, not striatal, activity fluctuations correlate with modulations in the increase/decrease discharge balance of BG downstream neurons during temporal discounting classical condition task. After induction of parkinsonism with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), abnormal low beta (8-15 Hz) spiking and local field potential (LFP) oscillations resonate across the BG network. Nevertheless, LFP beta oscillations entrain spiking activity of STN, striatal cholinergic interneurons and BG downstream structures, but do not entrain spiking activity of striatal projection neurons. Our results highlight the pivotal role of STN divergent projections in BG physiology and pathophysiology and may explain why STN is such an effective site for invasive treatment of advanced Parkinson's disease and other BG-related disorders.

Funder

The Edmond and Lily Safra Center

Ministry of Aliyah and Immigrant Absorption

The Teva National Network of Excellence in Neuroscience

The Israel-US Binational Science Foundation

The Adelis Foundation

European Research Council

Israel Science Foundation

The German Israel Science Foundation

The Canadian Friends of the Hebrew University

The Rosetrees and Vorst Foundations

The Simone and Bernard Guttman Chair in Brain Research

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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