The lateral reticular nucleus (LRN) in the medullary reticular formation is a major source of mossy fibres that project to most of the cerebellum. It receives convergent multimodal peripheral sensory information as well as descending input. Here we show that LRN neurones fire extremely regularly (mean coefficient of variation of interspike interval, 0.19 ± 0.1) in vivo in rats (~300g, urethane-anaesthetised, 1g/kg i.p.). LRN neurones responded to peripheral stimulus with an initial brief inhibition of firing followed by a resumption of spiking at a ‘reset’ timing. As this signal is broadcast divergently to the cerebellum it may be used for timing purposes or to generate oscillatory activity. We examined the effect of membrane hyperpolarisation on spike firing in whole-cell patch-clamp recordings from brain slices containing the LRN (prepared from rats aged postnatal day (P) 2 to P15, decapitated under halothane anaesthesia). Spontaneous regular firing was observed in LRN neurones in vitro (mean coefficient of variation of interspike interval, 0.38 ± 0.08), and could be driven to higher frequencies with depolarising current injections. Hyperpolarization of LRN neurones activated a time-dependent cation current and a corresponding time-dependent membrane depolarization. External Cs+ ions (3mM) and ZD7288 (50μM) inhibited the current activated by hyperpolarizing pulses from -70 to -100 mV by 83 ± 10 % (n=4) and 81 ± 4 % (n=13) respectively, consistent with it being the hyperpolarisation-activated cation current (Ih). A hyperpolarising pre-pulse to activate Ih significantly decreased the latency to first spike evoked by a subsequent depolarising pulse and introduced accommodation into the regular spike firing frequency. ZD7288 partially reversed the effect of the pre-pulse but had no effect on tonic spontaneous or driven firing. We conclude that Ih can accelerate the recovery of spiking after a hyperpolarising input but does not contribute to tonic pacemaking of spike firing in these neurons.
University of Manchester (2010) Proc Physiol Soc 19, C23
Oral Communications: Regulation of spike timing in neurones of the lateral reticular nucleus
W. Xu1, S. A. Edgley1, S. Jones1
1. Department of Physiology, Development and Neuroscience, Cambridge University, Cambridge, United Kingdom.
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