Opposing Actions of CRF-R1 and CB1 Receptor on Facial Stimulation-Induced MLI-PC Plasticity in Mouse Cerebellar Cortex

Abstract

Background Corticotropin-releasing factor (CRF) is an important neuromodulator in cerebellar cortex, which plays critical roles in modulating synaptic transmission and plasticity via its receptors. Activation of cannabinoid receptor 1 (CB1) controls the sensory stimulation-induced interneuron–Purkinje cell long-term depression (MLI-PC LTD) in mouse cerebellar cortex. However, the cellular actions of CRF on MLI-PC LTD are poor understand. We here investigated the effect of CRF on the facial stimulation-evoked MLI-PC long-term depression (LTD) in urethane-anesthetized mice by cell-attached recording technique and pharmacological method. Results Facial stimulation at 1Hz induced a LTD of MLI-PC synaptic transmission under control conditions, but it was not induced in the presence of CRF (100 nM). The CRF-abolished MLI-PC LTD was restored by a selective CRF-R1 antagonist, BMS-763534 (BMS, 200 nM), but it was not restored by a selective CRF-R2 antagonist, antisauvagine-30 (200 nM). Blocking cannabinoid type 1 (CB1) receptor, abolished the facial stimulation-induced MLI-PC LTD, and revealed a CRF-R1 receptor activation-dependent MLI-PC long-term potentiation (LTP). However, the CRF-R1 receptor activation-dependent MLI-PC LTP was abolished by inhibition of protein kinase C (PKC) with chelerythrine (5 µM) or depletion of intracellular Ca2+ with cyclopiazonic acid (100 µM). Conclusions The present results indicate that CRF opposes the CB1 receptor-dependent MLI-PC LTD produced by the facial stimulation train, which may be caused by triggering a MLI-PC LTP through CRF-R1/PKC and intracellular Ca2+ signaling pathway in mouse cerebellar cortex. Our results suggest that CRF-R1 and CB1 receptor play oppose actions on facial stimulation-induced cerebellar MLI-PC plasticity in vivo in mice.