ABSTRACT
The cerebellum receives sensory information by mossy fiber input from a multitude of sources that require differential signal processing. A compartmentalization of function begins with the segregation of mossy fibers across 10 distinct lobules over the rostrocaudal axis, with tactile receptor afferents prevalent in anterior lobules and vestibular input in caudal lobules. However, it is unclear how these unique signals might be differentially processed at the circuit level across the cerebellum. As granule cells receive mossy fiber input, they represent a key stage at which postsynaptic mechanisms could influence signal processing. Granule cells express an A-type current mediated by Kv4 potassium channels that modify the latency and frequency of spike output. The current study examined the potential for a Cav3 calcium-Kv4 channel complex to regulate the response of granule cells to mossy fiber input in lobules 2 and 9 of the rat cerebellum. Similar A-type currents were recorded in both regions, but the Cav3 calcium current was expressed at a substantially higher density in lobule 9 cells, acting to increase A-type current availability through its influence on Kv4 voltage for inactivation. The difference in excitability imparted by Cav3-Kv4 interactions proves to allow lobule 2 granule cells to respond more effectively to tactile stimulus-like burst input and lobule 9 cells to slow shifts in input frequency characteristic of vestibular input. The expression pattern of Cav3 channels and its control of Kv4 availability thus provides a novel means of processing widely different forms of sensory input across cerebellar lobules.
Subject(s)
Action Potentials/physiology , Caveolin 3/metabolism , Cerebellum/physiology , Neurons/physiology , Shal Potassium Channels/metabolism , Animals , Caveolin 3/genetics , Cerebellum/cytology , Cerebellum/metabolism , Neurons/cytology , Neurons/metabolism , Rats , Rats, Sprague-Dawley , Shal Potassium Channels/genetics , Synapses/metabolism , Synapses/physiologyABSTRACT
Synaptic transmission and neuronal excitability depend on the concentration of extracellular calcium ([Ca](o)), yet repetitive synaptic input is known to decrease [Ca](o) in numerous brain regions. In the cerebellar molecular layer, synaptic input reduces [Ca](o) by up to 0.4 mm in the vicinity of stellate cell interneurons and Purkinje cell dendrites. The mechanisms used to maintain network excitability and Purkinje cell output in the face of this rapid change in calcium gradient have remained an enigma. Here we use single and dual patch recordings in an in vitro slice preparation of Sprague Dawley rats to investigate the effects of physiological decreases in [Ca](o) on the excitability of cerebellar stellate cells and their inhibitory regulation of Purkinje cells. We find that a Ca(v)3-K(v)4 ion channel complex expressed in stellate cells acts as a calcium sensor that responds to a decrease in [Ca]o by dynamically adjusting stellate cell output to maintain inhibitory charge transfer to Purkinje cells. The Ca(v)3-K(v)4 complex thus enables an adaptive regulation of inhibitory input to Purkinje cells during fluctuations in [Ca](o), providing a homeostatic control mechanism to regulate Purkinje cell excitability during repetitive afferent activity.
