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Corticotrophin-Releasing Factor Modulates the Facial Stimulation-Evoked Molecular Layer Interneuron-Purkinje Cell Synaptic Transmission in vivo in Mice.

ABSTRACT: Corticotropin-releasing factor (CRF) is an important neuromodulator in central nervous system that modulates neuronal activity via its receptors during stress responses. In cerebellar cortex, CRF modulates the simple spike (SS) firing activity of Purkinje cells (PCs) has been previously demonstrated, whereas the effect of CRF on the molecular layer interneuron (MLI)-PC synaptic transmission is still unknown. In this study, we examined the effect of CRF on the facial stimulation-evoked cerebellar cortical MLI-PC synaptic transmission in urethane-anesthetized mice by in vivo cell-attached recording, neurobiotin juxtacellular labeling, immunohistochemistry techniques, and pharmacological method. Cell-attached recordings from cerebellar PCs showed that air-puff stimulation of ipsilateral whisker pad evoked a sequence of tiny parallel fiber volley (N1) followed by MLI-PC synaptic transmission (P1). Microapplication of CRF in cerebellar cortical molecular layer induced increases in amplitude of P1 and pause of SS firing. The CRF decreases in amplitude of P1 waveform were in a dose-dependent manner with the EC₅₀ of 241 nM. The effects of CRF on amplitude of P1 and pause of SS firing were abolished by either a non-selective CRF receptor antagonist, ?-helical CRF-(9-14), or a selective CRF-R1 antagonist, BMS-763534 (BMS, 200 nM), but were not prevented by a selective CRF-R2 antagonist, antisauvagine-30 (200 nM). Notably, application CRF not only induced a significant increase in spontaneous spike firing rate, but also produced a significant increase in the number of the facial stimulation-evoked action potential in MLIs. The effect of CRF on the activity of MLIs was blocked by the selective CRF-R1 antagonist, and the MLIs expressed the CRF-R1 imunoreactivity. These results indicate that CRF increases excitability of MLIs via CRF-R1, resulting in an enhancement of the facial stimulation-evoked MLI-PC synaptic transmission in vivo in mice.

SUBMITTER: Wu WY

PROVIDER: S-EPMC7726213 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Corticotrophin-Releasing Factor Modulates the Facial Stimulation-Evoked Molecular Layer Interneuron-Purkinje Cell Synaptic Transmission <i>in vivo</i> in Mice.

Wu Wen-Yuan WY Liu Yang Y Wu Mao-Cheng MC Wang Hong-Wei HW Chu Chun-Ping CP Jin Hua H Li Yu-Zi YZ Qiu De-Lai DL

Frontiers in cellular neuroscience 20201126

Corticotropin-releasing factor (CRF) is an important neuromodulator in central nervous system that modulates neuronal activity via its receptors during stress responses. In cerebellar cortex, CRF modulates the simple spike (SS) firing activity of Purkinje cells (PCs) has been previously demonstrated, whereas the effect of CRF on the molecular layer interneuron (MLI)-PC synaptic transmission is still unknown. In this study, we examined the effect of CRF on the facial stimulation-evoked cerebellar ...[more]

PMID: 33324165

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Project description:The noradrenergic fibers of the locus coeruleus, together with mossy fibers and climbing fibers, comprise the three types of cerebellar afferents that modulate the cerebellar neuronal circuit. We previously demonstrated that noradrenaline (NA) modulated synaptic transmission in the mouse cerebellar cortex via adrenergic receptors (ARs). In the present study, we investigated the effect of NA on facial stimulation-evoked cerebellar molecular layer interneuron (MLI)-Purkinje cell (PC) synaptic transmission in urethane-anesthetized mice using an in vivo cell-attached recording technique and a pharmacological method. MLI-PC synaptic transmission was induced by air-puff stimulation (duration: 60 ms) of the ipsilateral whisker pad, which exhibited positive components (P1 and P2) accompanied by a pause in simple spike activity. Cerebellar molecular layer application of NA (15 µM) decreased the amplitude and area under the curve of P1, and the pause in simple spike activity, but increased the P2/P1 ratio. The NA-induced decrease in P1 amplitude was concentration-dependent, and the half-inhibitory concentration was 10.94 µM. The NA-induced depression of facial stimulation-evoked MLI-PC GABAergic synaptic transmission was completely abolished by blockade of α-ARs or α2-ARs, but not by antagonism of α1-ARs or β-ARs. Bath application of an α2-AR agonist inhibited MLI-PC synaptic transmission and attenuated the effect of NA on the synaptic response. NA-induced depression of MLI-PC synaptic transmission was completely blocked by a mixture of α2A- and 2B-AR antagonists, and was abolished by inhibition of protein kinase A. In addition, electrical stimulation of the molecular layer evoked MLI-PC GABAergic synaptic transmission in the presence of an AMPA receptor antagonist, which was inhibited by NA through α2-ARs. Our results indicate that NA inhibits MLI-PC GABAergic synaptic transmission by reducing GABA release via an α2-AR/PKA signaling pathway.

Dataset Information

Corticotrophin-Releasing Factor Modulates the Facial Stimulation-Evoked Molecular Layer Interneuron-Purkinje Cell Synaptic Transmission in vivo in Mice.

Publications

Corticotrophin-Releasing Factor Modulates the Facial Stimulation-Evoked Molecular Layer Interneuron-Purkinje Cell Synaptic Transmission <i>in vivo</i> in Mice.

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