Abstract
Cerebellar climbing-fiber-mediated complex spikes originate from neurons in the inferior olive (IO), are critical for motor coordination, and are central to theories of cerebellar learning. Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels expressed by IO neurons have been considered as pacemaker currents important for oscillatory and resonant dynamics. Here, we demonstrate that in vitro, network actions of HCN1 channels enable bidirectional glutamatergic synaptic responses, while local actions of HCN1 channels determine the timing and waveform of synaptically driven action potentials. These roles are distinct from, and may complement, proposed pacemaker functions of HCN channels. We find that in behaving animals HCN1 channels reduce variability in the timing of cerebellar complex spikes, which serve as a readout of IO spiking. Our results suggest that spatially distributed actions of HCN1 channels enable the IO to implement network-wide rules for synaptic integration that modulate the timing of cerebellar climbing fiber signals.
Original language | English |
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Pages (from-to) | 1722-1733 |
Number of pages | 13 |
Journal | Cell Reports |
Volume | 22 |
Issue number | 7 |
Early online date | 13 Feb 2018 |
DOIs | |
Publication status | Published - Feb 2018 |
Bibliographical note
AcknowledgmentsThis work was supported by the Medical Research Council (G0501216), the Wellcome Trust (093295/Z/10/Z and 086602/Z/08/Z), and the BBSRC (Bb/H020284/1). We thank Paolo Puggioni for help with motion analysis and the IMPACT facility at the University of Edinburgh for imaging resources.
Data Availability Statement
Supplemental Information includes Supplemental Experimental Procedures,six figures, and two tables and can be found with this article online at
https://doi.org/10.1016/j.celrep.2018.01.069