Activation of _2A and _2B -adrenergic receptors inhibits tactile stimulation-evoked parallel fiber-Purkinje cell synaptic transmission in mouse cerebellar cortex

The mechanism by which alpha 2-adrenergic receptors (ARs) modulate the cerebellar parallel fiber-Purkinje cell (PF-PC) synaptic transmission is unclear. We investigated this issue using electrophysiological and neuropharmacological methods. Six- to eight-week-old ICR mice were used in the study. Under in vivo conditions, PF-PC synaptic transmission was evoked by facial stimulation of ipsilateral whisker pad, and recorded using cell-attached patch from PCs. Under in-vitro conditions, PF-PC synaptic transmission was evoked by electrical stimulation of the molecular layer in cerebellar slices, and was recorded using whole-cell recording from PCs. SR95531 (20 mu M) was added to the ACSF during all recordings to prevent GABAA receptor-mediated inhibition. Air-puff stimulation of the ipsilateral whisker pad in-vivo evoked simple spike (eSS) firing of cerebellar PCs. Microapplication of noradrenaline (15 mu M) to the molecular layer significantly decreased the numbers and frequency of eSS, an effect abolished by the alpha 2-AR antagonist. Microapplication of an alpha 2-AR agonist, UK14304 (1 mu M), significantly decreased the numbers of eSS in PCs, which was abolished by either alpha 2A- or alpha 2B-AR antagonist, but not by alpha 2C-AR antagonist. Under in-vitro conditions, application of UK 14304 significantly decreased the amplitude of PF-PC EPSCs and increased the paired-pulse ratio, which were abolished by either alpha 2A- or alpha 2B-AR antagonist. The present results indicate that activation of presynaptic alpha 2A- and alpha 2B-AR downregulates PF-PC synaptic transmission in mouse cerebellar cortex.