HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jphysiol.2008.156232v3    most recent 586/18/4501 jphysiol.2008.156232v2 jphysiol.2008.156232v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Liu, S. Articles by Friel, D. D. PubMed PubMed Citation Articles by Liu, S. Articles by Friel, D. D. Related Collections Neuroscience

¹ Department of Neurosciences, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4975, USA

Loss-of-function mutations in the gene encoding P/Q-type Ca²⁺ channels cause cerebellar ataxia in mice and humans, but the underlying mechanism(s) are unknown. These Ca²⁺ channels play important roles in regulating both synaptic transmission and intrinsic membrane properties, and defects in either could contribute to ataxia. Our previous work described changes in intrinsic properties and excitability of cerebellar Purkinje cells (PCs) resulting from the leaner mutation, which is known to reduce whole-cell Ca²⁺ currents in PCs and cause severe ataxia. Here we describe the impact of this mutation on excitatory synaptic transmission from parallel and climbing fibres (PFs, CFs) to PCs in acute cerebellar slices. We found that in leaner PCs, PF-evoked excitatory postsynaptic currents (PF-EPSCs) are 50% smaller, and CF-evoked EPSCs are 80% larger, than in wild-type (WT) mice. To investigate whether reduced presynaptic Ca²⁺ entry plays a role in attenuating PF-EPSCs in leaner mice, we examined paired-pulse facilitation (PPF). We found that PPF is enhanced in leaner, suggesting that reduced presynaptic Ca²⁺ entry reduces neurotransmitter release at these synapses. Short-term plasticity was unchanged at CF–PC synapses, suggesting that CF-EPSCs are larger in leaner PCs because of increased synapse number or postsynaptic sensitivity, rather than enhanced presynaptic Ca²⁺ entry. To investigate the functional impact of the observed EPSC changes, we also compared excitatory postsynaptic potentials (EPSPs) elicited by PF and CF stimulation in WT and leaner PCs. Importantly, we found that despite pronounced changes in PF- and CF-EPSCs, evoked EPSPs in leaner mice are very similar to those observed in WT animals. These 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. They also implicate other consequences of the leaner mutation as causes of abnormal cerebellar motor control in mutant mice.

(Received 1 May 2008; accepted after revision 28 July 2008; first published online 31 July 2008)
Corresponding author D. D. Friel: Department of Neurosciences, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4975, USA.  Email: david.friel{at}case.edu