Effect of Noradrenaline on the Facial Stimulation-Evoked Mossy Fiber-Granule Cell Synaptic Transmission in Mouse Cerebellar Cortex

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.

Ligand-Based Shielding Effect Induced Efficient Near-Infrared Electrochemiluminescence of Gold Nanoclusters and Its Sensing Application

“…Noradrenaline (NE) is a sort of crucial biogenic neurotransmitter in the human body, and its dysregulation is tightly involved in various neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, pheochromocytoma, etc. , whose level is crucial for monitoring and diagnosing diseases. , Moreover, noradrenaline is currently the most commonly used vasopressor agent in clinical applications for treating septic shock, cardiogenic shock, and hypovolemic shock; thus, the injected dose influences the drug effects. , Therefore, the detection of noradrenaline possesses important significance for clinical diagnosis and pharmaceutical quantification. Based on the superefficient and stable ECL behavior (Figure A) of the β-CD-Au NCs/TEA system and the effective quenching performance of NE toward the ECL system, a sensitive and convenient “signal off” sensor for the detection of NE was constructed by adding a series of concentrations of NE into the detection solution.…”

“…Noradrenaline (NE) is a sort of crucial biogenic neurotransmitter in the human body, and its dysregulation is tightly involved in various neurodegenerative diseases, such as Alzheimer's, Parkinson's, pheochromocytoma, etc., whose level is crucial for monitoring and diagnosing diseases. 43,44 Moreover, noradrenaline is currently the most commonly used vasopressor agent in clinical applications for treating septic shock, cardiogenic shock, and hypovolemic shock; thus, the injected dose influences the drug effects. 45,46 Therefore, the detection of noradrenaline possesses important significance for clinical diagnosis and pharmaceutical quantification.…”

Noradrenaline depresses facial stimulation-evoked cerebellar MLI-PC synaptic transmission via α2-AR/PKA signaling cascade in vivo in mice

“…NA depresses climbing fiber-PC and MF-GC synaptic transmission via α2-ARs 26 – 28 , and therefore we applied the α2-AR antagonist yohimbine (100 µM) to determine whether NA can inhibit MLI-PC synaptic transmission through activation of α2-ARs. The results showed that application of yohimbine completely abolished the inhibitory effect of NA on P1 (Fig.…”

“…Importantly, NAergic fibers form varicosities near the dendrites of PCs 38 , which indicates that NAergic afferents are critical for the regulation of PC activity and synaptic transmission in the cerebellar cortex 9 , 11 . Electrophysiological studies in living animals have demonstrated that NA depressed neuronal activity in the cerebellar cortex via the activation of α2-ARs 26 , 27 and also inhibited facial stimulation-evoked MF-GC synaptic transmission 28 . The present results showed that cerebellar surface micro-application of NA inhibits either facial stimulation- or electric stimulation-evoked MLI-PC synaptic transmission in a concentration-dependent manner, accompanied by a significant increase in the P2/P1 ratio.…”

“…Under in vivo conditions, NA enhances inhibitory inputs of PCs by exciting MLIs, leading to the inhibition of PCs 25 . Moreover, NA reduces glutamate release at climbing fiber-PC synapses 26 , 27 and depresses facial stimulation-evoked MF-GC synaptic transmission via the activation of α2-ARs 28 .…”