The leaner P/Q‐type calcium channel mutation renders cerebellar Purkinje neurons hyper‐excitable and eliminates Ca2+‐Na+ spike bursts

@article{Ovsepian2008TheLP,
  title={The leaner P/Q‐type calcium channel mutation renders cerebellar Purkinje neurons hyper‐excitable and eliminates Ca2+‐Na+ spike bursts},
  author={Saak V. Ovsepian and David D. Friel},
  journal={European Journal of Neuroscience},
  year={2008},
  volume={27}
}
  • S. Ovsepian, D. Friel
  • Published 18 December 2007
  • Chemistry, Medicine
  • European Journal of Neuroscience
The leaner mouse mutation of the Cacna1a gene leads to a reduction in P‐type Ca2+ current, the dominant Ca2+ current in Purkinje cells (PCs). Here, we compare the electro‐responsiveness and structure of PCs from age‐matched leaner and wild‐type (WT) mice in pharmacological isolation from synaptic inputs in cerebellar slices. We report that compared with WT, leaner PCs exhibit lower current threshold for Na+ spike firing, larger subthreshold membrane depolarization, rapid adaptation followed by… Expand
Impact of the leaner P/Q‐type Ca2+ channel mutation on excitatory synaptic transmission in cerebellar Purkinje cells
TLDR
Results suggest that changes in synaptic currents and intrinsic properties of PCs produced by the leaner mutation together maintain PC responsiveness to excitatory synaptic inputs and implicate other consequences of theLeaner mutation as causes of abnormal cerebellar motor control in mutant mice. Expand
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The leaner mutation enhances spontaneous synaptic inhibition of PCs, leading to transitory reductions in PC firing rate and increased spike rate variability, the first account of the functional consequences of a loss-of-function P/Q channel mutation on PC firing properties through altered GABAergic transmission. Expand
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  • K. Lee, J. Kim, +4 authors D. Kim
  • Biology, Medicine
  • The European journal of neuroscience
  • 2011
TLDR
Using whole‐cell patch‐clamp recordings, it is shown 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. Expand
Compensatory regulation of Cav2.1 Ca2+ channels in cerebellar Purkinje neurons lacking parvalbumin and calbindin D-28k.
TLDR
Increased inactivation due to molecular switching of Ca(v)2.1 beta-subunits may preserve normal activity-dependent Ca(2+) signals in the absence ofCa(2+)-buffering proteins in PV/CB(-/-) Purkinje neurons. Expand
Knockdown of Cav2.1 calcium channels is sufficient to induce neurological disorders observed in natural occurring Cacna1a mutants in mice.
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Whole cell current-clamp analysis demonstrates that the variety of spiking modes and intermodal transitions could be induced within the same neuronal population by injection of bias depolarizing or hyperpolarizing currents. Expand
Conditional Knockout of Cav2.1 Disrupts the Accuracy of Spatial Recognition of CA1 Place Cells and Spatial/Contextual Recognition Behavior
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Significant impairments shown in behavioral tasks requiring spatial and contextual information processing were statistically significant while general neurological behaviors did not differ between groups, providing potential evidence that Cav2.1 in hippocampal pyramidal cells modulates temporal integration of bursts, which, in turn, might influence the recognition of place field and consequently disrupt spatial recognition ability. Expand
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