Corticotrophin-Releasing Factor Modulates the Facial Stimulation-Evoked Molecular Layer Interneuron-Purkinje Cell Synaptic Transmission in vivo in Mice

Corticotropin-releasing factor (CRF) is an important neuromodulator in central nervous system that modulates neuronal activity via its receptors during stress responses. In cerebellar cortex, CRF modulates the simple spike (SS) firing activity of Purkinje cells (PCs) has been previously demonstrated, whereas the effect of CRF on the molecular layer interneuron (MLI)–PC synaptic transmission is still unknown. In this study, we examined the effect of CRF on the facial stimulation–evoked cerebellar cortical MLI-PC synaptic transmission in urethane-anesthetized mice by in vivo cell-attached recording, neurobiotin juxtacellular labeling, immunohistochemistry techniques, and pharmacological method. Cell-attached recordings from cerebellar PCs showed that air-puff stimulation of ipsilateral whisker pad evoked a sequence of tiny parallel fiber volley (N1) followed by MLI-PC synaptic transmission (P1). Microapplication of CRF in cerebellar cortical molecular layer induced increases in amplitude of P1 and pause of SS firing. The CRF decreases in amplitude of P1 waveform were in a dose-dependent manner with the EC50 of 241 nM. The effects of CRF on amplitude of P1 and pause of SS firing were abolished by either a non-selective CRF receptor antagonist, α-helical CRF-(9-14), or a selective CRF-R1 antagonist, BMS-763534 (BMS, 200 nM), but were not prevented by a selective CRF-R2 antagonist, antisauvagine-30 (200 nM). Notably, application CRF not only induced a significant increase in spontaneous spike firing rate, but also produced a significant increase in the number of the facial stimulation–evoked action potential in MLIs. The effect of CRF on the activity of MLIs was blocked by the selective CRF-R1 antagonist, and the MLIs expressed the CRF-R1 imunoreactivity. These results indicate that CRF increases excitability of MLIs via CRF-R1, resulting in an enhancement of the facial stimulation–evoked MLI-PC synaptic transmission in vivo in mice.

Short-term plasticity at cerebellar granule cell to molecular layer interneuron synapses expands information processing

Information processing by cerebellar molecular layer interneurons (MLIs) plays a crucial role in motor behavior. MLI recruitment is tightly controlled by the profile of short-term plasticity (STP) at granule cell (GC)-MLI synapses. While GCs are the most numerous neurons in the brain, STP diversity at GC-MLI synapses is poorly documented. Here, we studied how single MLIs are recruited by their distinct GC inputs during burst firing. Using slice recordings at individual GC-MLI synapses of mice, we revealed four classes of connections segregated by their STP profile. Each class differentially drives MLI recruitment. We show that GC synaptic diversity is underlain by heterogeneous expression of synapsin II, a key actor of STP and that GC terminals devoid of synapsin II are associated with slow MLI recruitment. Our study reveals that molecular, structural and functional diversity across GC terminals provides a mechanism to expand the coding range of MLIs.