Ketamine induced converged synchronous gamma oscillations in the cortico-basal ganglia network of nonhuman primates

Maya Slovik, Boris Rosin, Shay Moshel, Rea Mitelman, Eitan Schechtman, Renana Eitan, Aeyal Raz, Hagai Bergman

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

N-methyl-D-aspartate (NMDA) antagonists are widely used in anesthesia, pain management, and schizophrenia animal model studies, and recently as potential antidepressants. However, the mechanisms underlying their anesthetic, psychotic, cognitive, and emotional effects are still elusive. The basal ganglia (BG) integrate input from different cortical domains through their dopamine-modulated connections to achieve optimal behavior control. NMDA antagonists have been shown to induce gamma oscillations in human EEG recordings and in rodent cortical and BG networks. However, network relations and implications to the primate brain are still unclear. We recorded local field potentials (LFPs) simultaneously from the primary motor cortex (M1) and the external globus pallidus (GPe) of four vervet monkeys (26 sessions, 97 and 76 cortical and pallidal LFPs, respectively) before and after administration of ketamine (NMDA antagonist, 10 mg/kg im). Ketamine induced robust, spontaneous gamma (30–50 Hz) oscillations in M1 and GPe. These oscillations were initially modulated by ultraslow oscillations (~0.3 Hz) and were highly synchronized within and between M1 and the GPe (mean coherence magnitude = 0.76, 0.88, and 0.41 for M1-M1, GPe-GPe, and M1-GPe pairs). Phase differences were distributed evenly around zero with broad and very narrow distribution for the M1-M1 and GPe-GPe pairs (=3.5 = 31.8° and =0.4 = 6.0°), respectively. The distribution of M1-GPe phase shift was skewed to the left with a mean of =18.4 = 20.9°. The increased gamma coherence between M1 and GPe, two central stages in the cortico-BG loops, suggests a global abnormal network phenomenon with a unique spectral signature, which is enabled by the BG funneling architecture. NEW & NOTEWORTHY This study is the first to show spontaneous gamma oscillations under NMDA antagonist in nonhuman primates. These oscillations appear in synchrony in the cortex and the basal ganglia. Phase analysis refutes the confounding effects of volume conduction and supports the funneling and amplifying architecture of the cortico-basal ganglia loops. These results suggest an abnormal network phenomenon with a unique spectral signature that could account for pathological mental and neurological states.

Original languageEnglish
Pages (from-to)917-931
Number of pages15
JournalJournal of Neurophysiology
Volume118
Issue number2
DOIs
StatePublished - 1 Aug 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 the American Physiological Society.

Funding

This work was supported by research grants of the European Research Council, Adelis Foundation, Rostrees Foundation, and Vorst Family Foundation, and the Simone and Bernard Guttman Chair of Brain Research. M. Slovik was supported by a Converging Technologies scholarship of the Israeli Council for Higher Education and by a Hebrew University scholarship. S. Moshel was supported by the Edmond and Lily Safra Center postdoctoral fellowship. R. Mitelman was supported by the Hoffman Leadership and Responsibility fellowship program at the Hebrew University. A. Raz was supported by a grant from the International Anesthesia Research Society Mentored Research Award.

FundersFunder number
Edmond and Lily Safra Center
Hoffman Leadership and Responsibility
Rostrees Foundation
Vorst Family Foundation
Achelis Foundation
International Anesthesia Research Society
European Research Council
Hebrew University of Jerusalem
Council for Higher Education

    Keywords

    • Basal ganglia
    • Gamma oscillations
    • Ketamine
    • NMDA antagonist
    • PCP

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