The neuropeptide corticotropin-releasing factor regulates excitatory transmission and plasticity at the climbing fibre-Purkinje cell synapse.
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.
Schmolesky
M T
MT
Department of Neuroscience, Erasmus University Medical Centre, Postbus 2040, 3000 CA Rotterdam, The Netherlands.
De Ruiter
M M
MM
De Zeeuw
C I
CI
Hansel
C
C
D000818:Animals; D000831:Animals, Newborn; D002227:Carbazoles / Q000494:pharmacology; D002531:Cerebellum / Q000166:cytology; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology; D011689:Purkinje Cells / Q000166:cytology / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D010446:Peptide Fragments; D011758:Pyrroles; C104416:astressin; C057416:KT 5720; D003346:Corticotropin-Releasing Hormone