Altered Purkinje cell responses and calmodulin expression in the spontaneously ataxic mouse, Pogo

Ataxia is often associated with altered cerebellar motor control, a process in which Purkinje cells (PCs) play a principal role. Pogo mice display severe motor deficits characterized by an ataxic gait accompanying hindlimb hyperextension. Here, using whole‐cell patch‐clamp recordings, we show that p...

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Bibliographic Details
Published in:The European journal of neuroscience 2011-04, Vol.33 (8), p.1493-1503
Main Authors: Lee, Kwan Young, Kim, Jin Seong, Kim, Se Hoon, Park, Hyung Seo, Jeong, Young-Gil, Lee, Nam-Seob, Kim, Dong Kwan
Format: Article
Language:English
Subjects:
Action Potentials - physiology
Animals
Ataxia
Ataxia - metabolism
Ataxia - physiopathology
Calcium-binding protein
Calmodulin
Calmodulin - antagonists & inhibitors
Calmodulin - metabolism
Cerebellum
Cerebellum - cytology
Cerebellum - metabolism
electrophysiology
Excitatory postsynaptic potentials
Firing pattern
gait
Long-term depression
Long-Term Synaptic Depression - physiology
Mice
Mice, Mutant Strains
Motor task performance
Nervous system
Neuronal Plasticity - physiology
paired-pulse facilitation
parallel fibers
Patch-Clamp Techniques
Purkinje cells
Purkinje Cells - cytology
Purkinje Cells - physiology
Synapses - metabolism
Synaptic Transmission - physiology
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Summary:Ataxia is often associated with altered cerebellar motor control, a process in which Purkinje cells (PCs) play a principal role. Pogo mice display severe motor deficits characterized by an ataxic gait accompanying hindlimb hyperextension. Here, using whole‐cell patch‐clamp recordings, we show that parallel fiber (PF)‐excitatory post‐synaptic currents (PF‐EPSCs) are reduced, paired‐pulse facilitation (PPF) is increased and PF‐PC long‐term depression (LTD) is impaired in Pogo mice; in contrast, climbing‐fiber EPSCs are preserved. In control mice, treatment with the calmodulin antagonist calmidazolium (5 μm) impaired PPF and LTD. Notably, cerebellar calmodulin expression was significantly reduced in Pogo mice compared with control mice. Control PCs predominantly exhibited a tonic firing pattern, whereas the firing pattern in Pogo PCs was mainly a complex burst type. These results implicate alterations in PC responses and calmodulin content in the abnormal cerebellar function of Pogo mice.
ISSN:0953-816X
1460-9568
DOI:10.1111/j.1460-9568.2011.07641.x