Electrical Coupling and Synchronized Subthreshold Oscillations in the Inferior Olive of the Rhesus Macaque

Abstract

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.

Complex Spike Wars: a New Hope

“…One of the intriguing properties of the inferior olive neurons is the presence of gap junctions [ 73 , 74 ]. When combined with a set of voltage-gated calcium and potassium conductances, the electronic coupling supports the synchronous [ 75 – 78 ] and rhythmic activity of most inferior olive neurons (with the exception of neurons in the dorsal cap of Kooy). The 1–10-Hz oscillations occur in both the subthreshold membrane potential [ 79 , 80 ] and discharge of olivary neurons [ 81 – 84 ].…”

Neuronal Regulation of Fast Synaptotagmin Isoforms Controls the Relative Contributions of Synchronous and Asynchronous Release

“…Cells were held at À70 mV, and all experiments were performed in the presence of 5 mM NBQX to block AMPARs, 2.5 mM (R,S)-CPP to block NMDARs, and 0.5 mM strychnine to block glycine receptors. IO neurons have prominent subthreshold membrane potential oscillations (Lliná s and Yarom, 1981a, 1981b, 1986Turecek et al, 2016) and conditions were adjusted to minimize oscillatory activity. 1 mM TTA-P2 was included in the ACSF to block t-type Ca 2+ channels that can drive sub-threshold oscillations (Lliná s and Yarom, 1981b).…”

Membrane potential synchrony of neurons in anterior cingulate cortex plays a pivotal role in generation of neuropathic pain

“…Thus, our results may indicate that increases in V m cross-correlations after nerve injury contribute to the generation of neuropathic pain. The occurrence of endogenous membrane synchrony was demonstrated in different portions of the central nervous system including the neocortex 24 , entorhinal cortex 25 , thalamus 26 , amygdaloid complex 27 , and inferior olive 28 , 29 . Here, we demonstrated the existence of the membrane synchrony in the ACC using in vivo dual patch whole-cell recording.…”