Electrical Coupling and Synchronized Subthreshold Oscillations in the Inferior Olive of the Rhesus Macaque.
Inferior olive (IO) neurons are critical for motor coordination and exhibit oscillations in membrane potential that are subthreshold for spiking. The prevalence, coherence, and continuity of those subthreshold oscillations (STOs) depend upon resonant interactions between neighboring neurons supported by electrical coupling. Many studies of the olivocerebellar system in rodents, in which STOs were related to tremor, whisking, and licking, fueled a debate over whether IO STOs were relevant for primates whose repertoire of movement is generally less periodic. The debate was never well informed due to the lack of a direct examination of the physiological properties of primate IO neurons. Here, we obtained dual patch-clamp recordings of neighboring IO neurons from young adult macaques in brainstem slices and compared them to identical recordings from rats. Macaque IO neurons exhibited an equivalent prevalence of continuous STOs as rats (45 vs 54%, respectively). However, macaque STOs were slower (1-4 Hz) and did not overlap with the dominant 4-9 Hz frequency of rats. The slower STO frequency of macaques was at least partially due to a prolonged membrane time constant and increased membrane capacitance that could be attributed to stronger electrical coupling and greater total dendritic length. The presence of synchronized STOs in the IO of adult macaques, coincident with strong and prevalent electrical coupling, answers a fundamental outstanding question in cerebellar neuroscience and is consistent with a prominent role for synchronized oscillation in primate sensory-motor control.



It was debated whether inferior olive (IO) neurons of primates behave as synchronized oscillators as was found for rodents using intracellular, optical, and multielectrode recordings. An inability to resolve this issue using single-Purkinje cell extracellular recordings in monkeys limited our understanding of timing mechanisms in the primate brain. Using dual whole-cell recordings from the IO of young adult rhesus macaques in acutely prepared brainstem slices, our work demonstrates that pairs of primate IO neurons show synchronized oscillations in membrane potential. The findings have strong mechanistic and translational relevance, as IO activation has been implicated in humans' perceptual timing of sensory events and motricity.
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington 98101.
Josef
J
Turecek
Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington 98101.
Victor Z
VZ
Han
Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon 97006.
Verginia C
VC
Cuzon Carlson
Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon 97006, Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon 97239, and.
Kathleen A
KA
Grant
Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington 98101, Department of Pediatrics, University of Washington, Seattle, Washington 98195 john.welsh@seattlechildrens.org.
John P
JP
Welsh
D000818:Animals; D000831:Animals, Newborn; D001683:Biological Clocks / Q000502:physiology*; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D003712:Dendrites / Q000502:physiology; D004558:Electric Stimulation; D005260:Female; D017629:Gap Junctions / Q000502:physiology*; D066298:In Vitro Techniques; D008253:Macaca mulatta; D008297:Male; D008564:Membrane Potentials / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009847:Olivary Nucleus / Q000502:physiology*; D018408:Patch-Clamp Techniques
C070614:neurobiotin; D001710:Biotin
electrical synapse; inferior olive; oscillation; primate; synchrony