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Published on: December 19, 2013
Fentanyl Inhibits Air Puff-Evoked Sensory Information Processing in Mouse Cerebellar Neurons Recorded in vivo
He-Min Yang1,2, Li-Jie Zhan1,2, Xue-Qin Lin2
1Brain Science Research Center, Yanbian University, Yanji City, China.
Abstract:
Aim: To examine the effects of fentanyl, a potent mu-opioid receptor (MOR) agonist, on-air puff-evoked responses in Purkinje cells (PCs), and molecular layer interneurons (MLIs) using in vivo patch-clamp recordings in anesthetized mice. Methods: Male mice 6-8 weeks-old were anesthetized and fixed on a custom-made stereotaxic frame. The cerebellar surface was exposed and perfused with oxygenated artificial cerebrospinal fluid (ACSF). Patch-clamp recordings in the cell-attached mode were obtained from PCs and MLIs. Facial stimulation by air-puff of the ipsilateral whisker pad was performed through a pressurized injection system. Fentanyl citrate, CTOP, and H-89 dissolved in ACSF were perfused onto the cerebellar surface. Results: Fentanyl significantly inhibited the amplitude and area under the curve (AUC) of sensory stimulation-evoked inhibitory responses in PCs. Although fentanyl did not influence the frequency of simple spikes (SSs), it decreased the pause of SS. The IC50 of the fentanyl-induced suppression of the P1 response amplitude was 5.53 μM. The selective MOR antagonist CTOP abolished fentanyl-induced inhibitory responses in PCs. However, the application of CTOP alone increased the amplitude, AUC of P1, and the pause of SS. Notably, fentanyl significantly inhibited the tactile-evoked response of MLIs but did not affect their spontaneous firing. The fentanyl-induced decrease of inhibitory responses in PCs was partially prevented by a PKA inhibitor, H-89. Conclusions: These results suggest that fentanyl binds to MORs in MLIs to reduce GABAergic neurotransmission in MLI-PC projections and one potential mechanism is via modulation of the cAMP-PKA pathway.
Insights
Fentanyl suppresses sensory responses in cerebellar neurons by acting on mu-opioid receptors (MORs), potentially through the cAMP-protein kinase A pathway. This impacts Purkinje cells and interneurons, suggesting a novel mechanism for opioid effects.
Area of Science:
- Neuroscience
- Pharmacology
- Cellular Electrophysiology
Background:
- Fentanyl is a potent mu-opioid receptor (MOR) agonist with known central nervous system effects.
- Purkinje cells (PCs) and molecular layer interneurons (MLIs) are key components of cerebellar circuitry involved in motor control and sensory processing.
Purpose of the Study:
- To investigate the effects of fentanyl on air puff-evoked neuronal responses in cerebellar PCs and MLIs.
- To elucidate the role of MORs and the cAMP-protein kinase A (PKA) pathway in fentanyl's actions within the cerebellum.
Main Methods:
- In vivo patch-clamp recordings were performed on PCs and MLIs in anesthetized mice.
- Neuronal responses to air-puff stimulation of the whisker pad were measured.
- Fentanyl, the MOR antagonist CTOP, and the PKA inhibitor H-89 were applied to the cerebellar surface.
Main Results:
- Fentanyl significantly inhibited sensory-evoked inhibitory responses and decreased simple spike pauses in PCs.
- Fentanyl suppressed tactile-evoked responses in MLIs but did not alter their spontaneous firing.
- The MOR antagonist CTOP blocked fentanyl's effects and had independent modulatory actions, while H-89 partially prevented fentanyl's inhibitory effects on PCs.
Conclusions:
- Fentanyl acts on MORs in MLIs to reduce GABAergic neurotransmission onto PCs, thereby modulating cerebellar sensory processing.
- The cAMP-PKA pathway is implicated in the mechanism underlying fentanyl's inhibitory effects on cerebellar PCs.
