Long-Term Potentiation at the Mossy Fiber-Granule Cell Relay Invokes Postsynaptic Second-Messenger Regulation of Kv4 Channels.
Mossy fiber afferents to cerebellar granule cells form the primary synaptic relay into cerebellum, providing an ideal site to process signal inputs differentially. Mossy fiber input is known to exhibit a long-term potentiation (LTP) of synaptic efficacy through a combination of presynaptic and postsynaptic mechanisms. However, the specific postsynaptic mechanisms contributing to LTP of mossy fiber input is unknown. The current study tested the hypothesis that LTP induces a change in intrinsic membrane excitability of rat cerebellar granule cells through modification of Kv4 A-type potassium channels. We found that theta-burst stimulation of mossy fiber input in lobule 9 granule cells lowered the current threshold to spike and increases the gain of spike firing by 2- to 3-fold. The change in postsynaptic excitability was traced to hyperpolarizing shifts in both the half-inactivation and half-activation potentials of Kv4 that occurred upon coactivating NMDAR and group I metabotropic glutamatergic receptors. The effects of theta-burst stimulation on Kv4 channel control of the gain of spike firing depended on a signaling cascade leading to extracellular signal-related kinase activation. Under physiological conditions, LTP of synaptically evoked spike output was expressed preferentially for short bursts characteristic of sensory input, helping to shape signal processing at the mossy fiber-granule cell relay.



Cerebellar granule cells receive mossy fiber inputs that convey information on different sensory modalities and feedback from descending cortical projections. Recent work suggests that signal processing across multiple cerebellar lobules is controlled differentially by postsynaptic ionic mechanisms at the level of granule cells. We found that long-term potentiation (LTP) of mossy fiber input invoked a large increase in granule cell excitability by modifying the biophysical properties of Kv4 channels through a specific signaling cascade. LTP of granule cell output became evident in response to bursts of mossy fiber input, revealing that Kv4 control of intrinsic excitability is modified to respond most effectively to patterns of afferent input that are characteristic of physiological sensory patterns.
Department of Cell Biology and Anatomy.
Arsalan P
0000-0002-6901-1387
AP
Rizwan
Department of Cell Biology and Anatomy.
Xiaoqin
X
Zhan
Department of Physiology and Pharmacology, Hotchkiss Brain Institute, and.|Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
Gerald W
GW
Zamponi
Department of Cell Biology and Anatomy, rwturner@ucalgary.ca.|Department of Physiology and Pharmacology, Hotchkiss Brain Institute, and.
Ray W
RW
Turner
D000818:Animals; D002478:Cells, Cultured; D015640:Ion Channel Gating / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D009412:Nerve Fibers / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015290:Second Messenger Systems / Q000502:physiology*; D051672:Shal Potassium Channels / Q000378:metabolism*; D055366:Synaptic Potentials / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
D051672:Shal Potassium Channels
Kv4; cerebellum; granule cell; long-term potentiation; mossy fiber