Abstract
Noradrenaline is an important neuromodulator in the cerebellum. We previously found that noradrenaline depressed cerebellar Purkinje cell activity and climbing fiber–Purkinje cell synaptic transmission in vivo in mice. In this study, we investigated the effect of noradrenaline on the facial stimulation-evoked cerebellar cortical mossy fiber–granule cell synaptic transmission in urethane-anesthetized mice. In the presence of a γ-aminobutyrateA (GABAA) receptor antagonist, air-puff stimulation of the ipsilateral whisker pad evoked mossy fiber–granule cell synaptic transmission in the cerebellar granular layer, which expressed stimulus onset response, N1 and stimulus offset response, N2. Cerebellar surface perfusion of 25 μM noradrenaline induced decreases in the amplitude and area under the curve of N1 and N2, accompanied by an increase in the N2/N1 ratio. In the presence of a GABAA receptor blocker, noradrenaline induced a concentration-dependent decrease in the amplitude of N1, with a half-maximal inhibitory concentration of 25.45 μM. The noradrenaline-induced depression of the facial stimulation-evoked mossy fiber–granule cell synaptic transmission was reversed by additional application of an alpha-adrenergic receptor antagonist or an alpha-2 adrenergic receptor antagonist, but not by a beta-adrenergic receptor antagonist or an alpha-1 adrenergic receptor antagonist. Moreover, application of an alpha-2 adrenergic receptor agonist, UK14304, significantly decreased the synaptic response and prevented the noradrenaline-induced depression. Our results indicate that noradrenaline depresses facial stimulation-evoked mossy fiber–granule cell synaptic transmission via the alpha-2 adrenergic receptor in vivo in mice, suggesting that noradrenaline regulates sensory information integration and synaptic transmission in the cerebellar cortical granular layer.
Highlights
The cerebellar cortex acquires information from three classes of afferents: mossy fibers (MFs), climbing fibers, and multilayered fibers, and generates motor-related output by Purkinje cells (PCs) (Haines and Dietrichs, 2002)
We showed that cerebellar surface perfusion of NA induced a concentration-dependent depression of facial stimulation-evoked MF-granule cell (GC) synaptic transmission, which was reversed by additional application of an α-adrenergic receptor (AR) antagonist but not reversed by a β-AR antagonist
The NAinduced inhibition of facial stimulation-evoked MF-GC synaptic transmission was reversed by additional application of an α2AR antagonist but not by an α1-AR antagonist
Summary
The cerebellar cortex acquires information from three classes of afferents: mossy fibers (MFs), climbing fibers, and multilayered fibers, and generates motor-related output by Purkinje cells (PCs) (Haines and Dietrichs, 2002). Granule cells (GCs) exhibit a low frequency of spontaneous firing, but they are very sensitive to sensory stimulation (van Beugen et al, 2013). NA-activated presynaptic α2-AR regulated climbing fiber–PC synaptic transmission via the PKA signaling pathway, suggesting that the NAergic fibers from the nucleus of the LC might regulate the output behavior of PC by suppressing the information transmission from the inferior olivary nucleus to the cerebellar cortex in vivo in mice (Sun et al, 2019; Cui et al, 2020). In this study, we combined electrophysiological and pharmacological approaches to investigate the effects of NA on the facial stimulation-evoked MF-GC synaptic transmission in the absence the GABAergic inhibition in urethane-anesthetized mice
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