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Key points • The lateral reticular nucleus (LRN) sends dense mossy fibre projections to the cerebellum. We report that LRN neurons convey timing signals that, along with measurements of force and distance, are needed for the cerebellum to organise movement. • We show that LRN neurons fire with clock-like regularity but pause their firing in response to peripheral sensory stimuli; regular firing then resumes at a new, ‘reset’ time. Thus, the firing properties of LRN neurons enable them to signal the timing of sensory events to the cerebellum over prolonged periods. • We show a plausible ionic mechanism for these properties of LRN neurons, involving the concerted activity of the hyperpolarisation-activated cation conductance (Ih) and the small-conductance calcium-activated potassium conductance (SK). Notably, Ih shortens the latency and sharpens the precision of post-inhibitory spiking. • Overall, we provide evidence for a potential mechanism of time representation in a neural circuit. Abstract Time representation is an important element of cerebellar neural processing, but the mechanisms involved are poorly understood. We demonstrate that the major mossy fibre input system originating from the lateral reticular nucleus (LRN) can represent sensory event timing over hundreds of milliseconds. In vivo, cerebellar-projecting LRN neurons discharge extremely regularly with a clock-like rhythm. In response to stimulation of a wide peripheral receptive field, firing briefly pauses then resumes with precise timing. The precision of post-stimulus spikes and the regularity of firing mean that the stimulus timing is represented by LRN spike timing over hundreds of milliseconds. In an arithmetic progression model of LRN neuron firing, highly predictable post-stimulus spike timing is modulated by changing the variability of the first post-inhibitory spike and of the subsequent interspike intervals. From in vitro analysis we show that the Ca2+-activated small-conductance K+ current (SK) contributes to interspike interval regularity and that the hyperpolarization-activated cation current (Ih) contributes to short-latency, high-precision post-hyperpolarisation spike timing. Consistent with this, we demonstrate in vivo that resumption of firing becomes more sharply timed after longer stimulus-evoked pauses. Thus, Ih is a potential conductance that could mediate the precisely timed resumption of firing after the pause. Through the widespread projections of LRN neurons, these properties may enable the LRN to provide precisely timed signals to the cerebellum over a prolonged period following a stimulus, which may also both activate and sustain oscillatory processes in the cerebellar cortex. |
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