Ten-Hour Exposure to Low-Dose Ketamine Enhances Corticostriata Cross-Frequency Coupling and Hippocampal Broad-Band Gamma Oscillations
Bartlett, Mitchell J.
Schmit, Matthew B.
Sherman, Scott J.
Cowen, Stephen L.
AffiliationUniv Arizona, Dept Psychol
Univ Arizona, Coll Med, Dept Pharmacol
Univ Arizona, Coll Med, Dept Neurol
Univ Arizona, Grad Interdisciplinary Program Neurosci
MetadataShow full item record
PublisherFRONTIERS MEDIA SA
CitationYe T, Bartlett MJ, Schmit MB, Sherman SJ, Falk T and Cowen SL (2018) Ten-Hour Exposure to Low-Dose Ketamine Enhances Corticostriatal Cross-Frequency Coupling and Hippocampal Broad-Band Gamma Oscillations. Front. Neural Circuits 12:61. doi: 10.3389/fncir.2018.00061
JournalFRONTIERS IN NEURAL CIRCUITS
Rights© 2018 Ye, Bartlett, Schmit, Sherman, Falk and Cowen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at email@example.com.
AbstractIntroduction: Treatment-resistant depression, post-traumatic stress disorder, chronic pain, and L-DOPA-induced dyskinesia in Parkinson's disease are characterized by hypersynchronous neural oscillations. Sub-anesthetic ketamine is effective at treating these conditions, and this may relate to ketamine's capacity to reorganize oscillatory activity throughout the brain. For example, a single ketamine injection increases gamma (similar to 40 Hz) and high-frequency oscillations (HFOs, 120-160 Hz) in the cortex, hippocampus, and striatum. While the effects of single injections have been investigated, clinical ketamine treatments can involve 5-h up to 3-day sub-anesthetic infusions. Little is known about the effects of such prolonged exposure on neural synchrony. We hypothesized that hours-long exposure entrains circuits that generate HFOs so that HFOs become sustained after ketamine's direct effects on receptors subside. Methods: Local-field recordings were acquired from motor cortex (M1), striatum, and hippocampus of behaving rats (n = 8), and neural responses were measured while rats received 5 ketamine injections (20 mg/kg, i.p., every 2 h, 10-h exposure). In a second experiment, the same animals received injections of D1-receptor antagonist (SCH-23390, 1 mg/kg, i.p.) prior to ketamine injection to determine if D1 receptors were involved in producing HFOs. Results: Although HFOs remained stable throughout extended ketamine exposure, broad-band high-frequency activity (40-140 Hz) in the hippocampus and delta-HFO cross-frequency coupling (CFC) in dorsal striatum increased with the duration of exposure. Furthermore, while ketamine-triggered HFOs were not affected by D1 receptor blockade, ketamine-associated gamma in motor cortex was suppressed, suggesting involvement of D1 receptors in ketamine-mediated gamma activity in motor cortex. Conclusion: Prolonged ketamine exposure does not enhance HFOs in corticostriatal circuits, but, instead, enhances coordination between low and high frequencies in the striatum and reduces synchrony in the hippocampus. Increased striatal CFC may facilitate spike-timing dependent plasticity, resulting in lasting changes in motor activity. In contrast, the observed wide-band high-frequency "noise" in the hippocampus suggests that ketamine disrupts action-potential timing and reorganizes connectivity in this region. Differential restructuring of corticostriatal and limbic circuits may contribute to ketamine's clinical benefits.
NoteOpen access journal.
VersionFinal published version
SponsorsJerry T. and Glenda G. Jackson Fellowship in Parkinson's Research; Evelyn F. McKnight Brain Institute; NIH [T35HL007479]
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