Noradrenaline inhibits complex spikes activity via the presynaptic PKA signaling pathway in mouse cerebellar slices

• Published in: Neuroscience letters 2020-06, Vol.729, p.135008-135008, Article 135008
• Main Authors: Cui, Li-Na, Sun, Na, Li, Bing-Xue, Wang, Li-Fei, Zhang, Xin-Yuan, Qiu, De-Lai, Chu, Chun-Ping
• Format: Article
• Language: English
• Subjects: Acute cerebellar slice; Animals; Axons - drug effects; Cerebellum - drug effects; Cerebellum - physiology; Complex spikes; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Mice; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; Noradrenaline (NA); Norepinephrine - pharmacokinetics; Protein kinase A (PKA); Purkinje Cells - drug effects; Purkinje Cells - physiology; Signal Transduction - drug effects; Synapses - drug effects; Synapses - physiology; Synaptic Transmission - drug effects; Whole-cell recording
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2020.135008

•NA depressed the amplitude of CF-PC transmission and increased paired-pulse ratio.•Inhibition of protein kinase A prevented NA-induced inhibition of CF-PC transmission.•The NA-induced inhibition of CF-PC transmission was dependent on adenylate cyclase. Norepinephrine (NA) is an important neurotransmitter of the cerebellum that regulates synaptic transmission, motor regulation and motor learning under certain conditions via adrenergic receptors (ARs). We previously found that NA depressed cerebellar climbing fiber–Purkinje cell (CF-PC) synaptic transmission via α2-ARs in vivo in mice. We here investigated the mechanisms of NA inhibited CF-PC synaptic transmission in acute cerebellar slices using the whole-cell recording technique and pharmacological methods. Bath application of NA (10 μM) depressed CF-PC synaptic transmission, which exhibited a time-dependent decrease in amplitude of excitatory postsynaptic currents (N1), accompanied by an increase in the paired-pulse ratio (PPR). The NA-induced depression of CF-PC synaptic transmission was significantly prevented by inhibition of protein kinase A (PKA) with either H-89 or KT5720. Furthermore, the NA-induced inhibition of CF-PC synaptic transmission was rescued by activation adenylate cyclase (AC), and the AC-induced enhancement of CF-PC synaptic transmission was depressed by NA. Moreover, inhibition of AC with SQ22536, produced a significant depression of CF-PC synaptic transmission and abrogated the NA-induced depression of CF-PC synaptic transmission. However, the NA-induced depression of CF-PC synaptic transmission was not blocked by intracellular inhibition of PKA with a cell impermeable PKA inhibitor, PKI, or by extracellular inhibition of protein kinase C. These results indicate that NA activates presynaptic α2-AR, resulting in a depression of mouse cerebellar CF-PC synaptic transmission through the AC-PKA signaling pathway.