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The neuropeptide corticotropin‐releasing factor regulates excitatory transmission and plasticity at the climbing fibre‐Purkinje cell synapse
Author(s) -
Schmolesky M. T.,
De Ruiter M. M.,
De Zeeuw C. I.,
Hansel C.
Publication year - 2007
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2007.05409.x
Subject(s) - excitatory postsynaptic potential , neuroscience , postsynaptic potential , synapse , climbing fiber , chemistry , neurotransmission , protein kinase c , nmda receptor , synaptic plasticity , biology , microbiology and biotechnology , cerebellum , purkinje cell , inhibitory postsynaptic potential , receptor , kinase , biochemistry
The climbing fibre (CF) input controls cerebellar Purkinje cell (PC) activity as well as synaptic plasticity at parallel fibre (PF)‐PC synapses. Under high activity conditions, CFs release not only glutamate, but also the neuropeptide corticotropin‐releasing factor (CRF). Brief periods of such high CF activity can lead to the induction of long‐term depression (LTD) at CF‐PC synapses. Thus, we have examined for the first time the role of CRF in regulating excitatory postsynaptic currents (EPSCs) and long‐term plasticity at this synapse. Exogenous application of CRF alone transiently mimicked three aspects of CF‐LTD, causing reductions in the CF‐evoked excitatory postsynaptic current, complex spike second component and complex spike afterhyperpolarization. The complex spike first component is unaffected by CF‐LTD induction and was similarly unaffected by CRF. Application of a CRF receptor antagonist reduced the expression amplitude and induction probability of CF‐LTD monitored at the EPSC level. Collectively, these results suggest that under particular sensorimotor conditions, co‐release of CRF from climbing fibres could down‐regulate excitatory transmission and facilitate LTD induction at CF‐PC synapses. Inhibition of either protein kinase C (PKC) or protein kinase A (PKA) attenuated the effects of CRF upon CF‐EPSCs. We have previously shown that CF‐LTD induction is PKC‐dependent, and here demonstrate PKA‐dependence as well. These results suggest that both the acute effects of CRF on CF‐EPSCs as well as the facilitating effect of CRF on CF‐LTD induction can be explained by a CRF‐mediated recruitment of PKC and PKA.