Enhanced cerebellar climbing fiber-Purkinje cell synaptic transmission via corticotropin-releasing factor receptor 2 during the chronic phase of spinal cord injury mice.

Spinal cord injury (SCI) causes interruption of external information input from the spinal cord to the cerebellum. We here investigated the effect of SCI on mouse cerebellar climbing fiber-Purkinje cell (CF-PC) synaptic transmission. The SCI was caused at T10 using 6-week-old ICR mice. Mice recovered 4 weeks after surgery, the spontaneous complex spike (CS) activity of PC was recorded using cell-attached recording and whole-cell recording method in urethane-anesthetized mice cerebellar Crus II. The CF-PC excitatory postsynaptic currents (EPSCs) were evoked by paired electrical stimulation of CF in cerebellar slices to evaluate the changes of CF-PC synaptic transmission and paired-pulse ratio (PPR). The results showed that the number of spikelets, duration of spontaneous CS, and pause of simple spike firing were significantly increased in SCI than that in sham group. Application of a nonselective corticotropin-releasing factor receptor (CRF-R) antagonist significantly decreased spontaneous CS activity in SCI group but not in sham group. The enhanced CS activity in SCI mice was significantly decreased by a selective CRF-R2 antagonist but not a specific CRF-R1 antagonist. The amplitude of CF-PC EPSC1 was large accompanied by a lower PPR in SCI group than that in sham group. Blockade of CRF-R2 antagonist significantly decreased the amplitude of EPSC1 and increased PPR in SCI group. SCI induces enhancement of the spontaneous CS activity and CF-PC synaptic transmission via CRF-R2 in mouse cerebellar cortex, which suggests that remodeling of CF-PC synaptic transmission occurred in cerebellar cortex after SCI.