Abstract
Inferior olivary activity causes both short-term and long-term changes in cerebellar output underlying motor performance and motor learning. Many of its neurons engage in coherent subthreshold oscillations and are extensively coupled via gap junctions. Studies in reduced preparations suggest that these properties promote rhythmic, synchronized output. However, the interaction of these properties with torrential synaptic inputs in awake behaving animals is not well understood. Here we combine electrophysiological recordings in awake mice with a realistic tissue-scale computational model of the inferior olive to study the relative impact of intrinsic and extrinsic mechanisms governing its activity. Our data and model suggest that if subthreshold oscillations are present in the awake state, the period of these oscillations will be transient and variable. Accordingly, by using different temporal patterns of sensory stimulation, we found that complex spike rhythmicity was readily evoked but limited to short intervals of no more than a few hundred milliseconds and that the periodicity of this rhythmic activity was not fixed but dynamically related to the synaptic input to the inferior olive as well as to motor output. In contrast, in the long-term, the average olivary spiking activity was not affected by the strength and duration of the sensory stimulation, while the level of gap junctional coupling determined the stiffness of the rhythmic activity in the olivary network during its dynamic response to sensory modulation. Thus, interactions between intrinsic properties and extrinsic inputs can explain the variations of spiking activity of olivary neurons, providing a temporal framework for the creation of both the short-term and long-term changes in cerebellar output.
Highlights
A multitude of behavioral studies leave little doubt that the olivo-cerebellar system organizes appropriate timing in motor behavior [1,2,3], perceptual function [4,5,6] and motor learning [7,8,9,10]
Activity of the inferior olive, transmitted via climbing fibers to the cerebellum, regulates initiation and amplitude of movements, signals unexpected sensory feedback, and directs cerebellar learning. It is characterized by widespread subthreshold oscillations and synchronization promoted by strong electrotonic coupling
Subthreshold oscillations gate which inputs can be transmitted by inferior olivary neurons and which will not—dependent on the phase of the oscillation
Summary
A multitude of behavioral studies leave little doubt that the olivo-cerebellar system organizes appropriate timing in motor behavior [1,2,3], perceptual function [4,5,6] and motor learning [7,8,9,10]. At the core of the controversy is the question whether inferior olive cells are oscillating during the awake state and whether these oscillations affect the timing of the inferior olivary output [17,18,19]. The inferior olive is the sole source of the climbing fibers, the activity of which dictates complex spike firing by cerebellar Purkinje cells (for review, see [20]). Climbing fiber activity is essential for motor coordination, as it contributes to both initiation and learning of movements [8, 10, 21,22,23,24,25,26], and it may be involved in sensory processing and regulating more cognitive tasks [27,28,29,30]. Understanding the systemic consequences of inferior olivary spiking is of great importance
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