Norepinephrine (NE) modulates synaptic transmission and long-term plasticity through distinct subtype adrenergic receptor (AR)-mediated-intracellular signaling cascades. However, the role of NE modulates glutamatergic long-term potentiation (LTP) in the hypothalamic paraventricular nucleus (PVN) magnocellular neuroendocrine cells (MNCs) is unclear. We here investigate the effect of NE on high frequency stimulation (HFS)-induced glutamatergic LTP in rat hypothalamic PVN MNCs , by whole-cell patch-clamp recording, biocytin staining and pharmacological methods.
View Article and Find Full Text PDFValproic acid (VPA) is one of the most effective antiepileptic drugs, and exposing animals to VPA during gestation has been used as a model for autism spectrum disorder (ASD). Numerous studies have shown that impaired synaptic transmission in the cerebellar cortical circuits is one of the reasons for the social deficits and repetitive behavior seen in ASD. In this study, we investigated the effect of VPA exposure during pregnancy on tactile stimulation-evoked cerebellar mossy fiber-granule cell (MF-GC) synaptic transmission in mice anesthetized with urethane.
View Article and Find Full Text PDFEtomidate (ET) is a widely used intravenous imidazole general anesthetic, which depresses the cerebellar neuronal activity by modulating various receptors activity and synaptic transmission. In this study, we investigated the effects of ET on the cerebellar climbing fiber-Purkinje cells (CF-PC) plasticity in vitro in mice using whole-cell recording technique and pharmacological methods. Our results demonstrated that CF tetanic stimulation produced a mGluR1-dependent long-term depression (LTD) of CF-PC excitatory postsynaptic currents (EPSCs), which was enhanced by bath application of ET (10 µM).
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFIntroduction: Complex spikes (CSs) activity of cerebellar Purkinje cells plays critical roles in motor coordination and motor learning by transferring information to cerebellar cortex, which is an accessible and useful model for neurophysiological investigation. Etomidate is an ultrashort-acting nonbarbiturate intravenous anesthetic, which inhibits the spontaneous activity of cerebellar Purkinje cells through activation of GABAA and glycine receptors in vivo in mice. However, the effect of etomidate on the spontaneous CSs activity of cerebellar Purkinje cells in living mouse is not clear.
View Article and Find Full Text PDFGlucagon-like peptide-1 (GLP-1) is mainly secreted by preproglucagon neurons; it plays important roles in modulating neuronal activity and synaptic transmission through its receptors. In the present study, we investigated the effects of GLP-1 on parallel fiber-Purkinje cell (PF-PC) synaptic transmission in mouse cerebellar slices using whole-cell patch-clamp recording and pharmacology methods. In the presence of a γ-aminobutyric acid type A receptor antagonist, bath application of GLP-1 (100 nM) enhanced PF-PC synaptic transmission, with an increased amplitude of evoked excitatory postsynaptic synaptic currents (EPSCs) and a decreased paired-pulse ratio.
View Article and Find Full Text PDFGlucagon-like peptide-1 (GLP-1) is mainly secreted by preglucagonergic neurons in the nucleus tractus solitarius, which plays critical roles in regulation of neuronal activity in the central nervous system through its receptor. In the cerebellar cortex, GLP-1 receptor is abundantly expressed in the molecular layer, Purkinje cell (PC) layer and granular layer, indicating that GLP-1 may modulate the cerebellar neuronal activity. In this study, we investigated the mechanism by which GLP1 modulates mouse cerebellar PC activity .
View Article and Find Full Text PDFNicotine is a psychoactive component of tobacco that plays critical roles in the regulation of neuronal circuit function and neuroplasticity and contributes to the improvement of working memory performance and motor learning function nicotinic acetylcholine receptors (nAChRs). Under conditions, nicotine enhances facial stimulation-evoked mossy fiber-granule cell (MF-GrC) synaptic transmission, which suggests that nicotine regulates MF-GrC synaptic plasticity in the mouse cerebellar cortex. In this study, we investigated the effects of nicotine on facial stimulation-induced long-term potentiation (LTP) of MF-GrC synaptic transmission in urethane-anesthetized mice.
View Article and Find Full Text PDFCerebellar Purkinje cells (PCs) exhibit two types of discharge activities: simple spike (SS) and complex spike (CS). Previous studies found that noradrenaline (NA) can inhibit CS and bidirectionally regulate SS, but the enhancement of NA on SS is overwhelmed by the strong inhibition of excitatory molecular layer interneurons. However, the mechanism underlying the effect of NA on SS discharge frequency is not clear.
View Article and Find Full Text PDFBackground: Corticotropin-releasing factor (CRF) is the major neuromodulator orchestrating the stress response, and is secreted by neurons in various regions of the brain. Cerebellar CRF is released by afferents from inferior olivary neurons and other brainstem nuclei in response to stressful challenges, and contributes to modulation of synaptic plasticity and motor learning behavior via its receptors. We recently found that CRF modulates facial stimulation-evoked molecular layer interneuron-Purkinje cell (MLI-PC) synaptic transmission via CRF type 1 receptor (CRF-R1) in vivo in mice, suggesting that CRF modulates sensory stimulation-evoked MLI-PC synaptic plasticity.
View Article and Find Full Text PDFLong-term synaptic plasticity in the cerebellar cortex is a possible mechanism for motor learning. Previous studies have demonstrated the induction of mossy fiber-granule cell (MF-GrC) synaptic plasticity under and conditions, but the mechanisms underlying sensory stimulation-evoked long-term synaptic plasticity of MF-GrC in living animals are unclear. In this study, we investigated the mechanism of long-term potentiation (LTP) of MF-GrC synaptic transmission in the cerebellum induced by train of facial stimulation at 20 Hz in urethane-anesthetized mice using electrophysiological recording, immunohistochemistry techniques, and pharmacological methods.
View Article and Find Full Text PDFCorticotropin releasing factor (CRF) type 2 receptor (CRF-R2) is present in climbing fiber (CF) afferents, which involves in modulating the CF-Purkinje cell (PC) synaptic transmission in cerebellar cortex. However, the role of CRF-R2 in regulating CF-PC synaptic transmission is unclear. We here investigate the role of CRF-R2 in modulating PC complex spikes (CSs) activity and CF-PC synaptic transmission using electrophysiological recording techniques and pharmacological methods.
View Article and Find Full Text PDFNicotine modulates cerebellar physiology function by interacting with nicotinic acetylcholine receptors (nAChRs) and is involved in modulation of cerebellar cortical circuitry functions. Here, we investigated the effect of nicotine on sensory stimulation-evoked molecular layer interneuron-Purkinje cell (MLI-PC) synaptic transmission mouse cerebellar cortex using in vivo cell-attached recording technique and pharmacological methods. The results show that micro-application of nicotine to the cerebellar molecular layer significantly decreased sensory stimulation-evoked MLI-PC synaptic transmission in mouse cerebellar cortex.
View Article and Find Full Text PDFCerebellar Purkinje cells (PCs) play critical roles in motor coordination and motor learning through their simple spike (SS) activity. Previous studies have shown that chronic ethanol exposure (CEE) in adolescents impairs learning, attention, and behavior, at least in part by impairing the activity of cerebellar PCs. In this study, we investigated the effect of CEE on the SS activity in urethane-anesthetized adolescent mice by in vivo electrophysiological recordings and pharmacological methods.
View Article and Find Full Text PDFNoradrenaline 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 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.
View Article and Find Full Text PDFSensory information is transferred to the cerebellar cortex the mossy fiber-granule cell (MF-GC) pathway, which participates in motor coordination and motor learning. We previously reported that chronic ethanol exposure from adolescence facilitated the sensory-evoked molecular layer interneuron-Purkinje cell synaptic transmission in adult mice . Herein, we investigated the effect of chronic ethanol exposure from adolescence on facial stimulation-evoked MF-GC synaptic transmission in the adult mouse cerebellar cortex using electrophysiological recording techniques and pharmacological methods.
View Article and Find Full Text PDFFentanyl as a synthetic opioid works by binding to the mu-opioid receptor (MOR) in brain areas to generate analgesia, sedation and reward related behaviors. As we know, cerebellum is not only involved in sensory perception, motor coordination, motor learning and precise control of autonomous movement, but also important for the mood regulation, cognition, learning and memory. Previous studies have shown that functional MORs are widely distributed in the cerebellum, and the role of MOR activation in cerebellum has not been reported.
View Article and Find Full Text PDFCorticotropin-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 cell-attached recording, neurobiotin juxtacellular labeling, immunohistochemistry techniques, and pharmacological method.
View Article and Find Full Text PDF: 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 patch-clamp recordings in anesthetized mice. : 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).
View Article and Find Full Text PDFPropofol is generally used for the induction and maintenance of anesthesia in clinical procedures via activation of γ -aminobutyric acid A (GABA) receptors. When administered at the clinical dose, propofol use is associated with movement disorders, including dystonia and ataxia, suggesting that propofol administration impacts the function of cerebellar neuronal circuitry. In this study, we investigated the effect of propofol on climbing fiber (CF)-Purkinje cell (PC) synaptic transmission in mouse cerebellar slices in the absence of GABAergic inhibition using a whole-cell recording technique and pharmacological methods.
View Article and Find Full Text PDFN-methyl-D-aspartate receptors (NMDARs) are expressed in granule cell and involve in mossy fiber-granule cell (MF-GC) synaptic transmission in cerebellar cortex. In the absence GABA receptor activity, we here studied the role of NMDARs during the facial stimulation evoked MF-GC synaptic transmission in urethane-anesthetized mice using electrophysiological recording technique and pharmacological methods. Our results showed that facial stimuli train (20 Hz, 5 pulses) evoked 5 field potential responses (N1-N5) in mouse cerebellar granular layer, which identified MF-GC synaptic transmission.
View Article and Find Full Text PDFNorepinephrine (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.
View Article and Find Full Text PDFEthanol (EtOH) exposure causes alterations of motor coordination, balance, behavior, speech, and certain cognitive functions are considered to be caused partly by impairment of cerebellar circuits function and modulation of synaptic transmission. The cerebellar cortical molecular layer interneuron-Purkinje cell (MLI-PC) synapses are critical for various information integration and transmission, which are sensitive to acute and chronic EtOH exposure. The aim of this study is to investigate the effect of chronic ethanol exposure on the facial stimulation-evoked MLI-PC synaptic transmission in urethane-anesthetized mice, by electrophysiological recording and pharmacological methods.
View Article and Find Full Text PDFDendritic spine development is crucial for the establishment of excitatory synaptic connectivity and functional neural circuits. Alterations in spine morphology and density have been associated with multiple neurological disorders. Autism candidate gene disconnected-interacting protein homolog 2 A (DIP2A) is known to be involved in acetylated coenzyme A (Ac-CoA) synthesis and is primarily expressed in the brain regions with abundant pyramidal neurons.
View Article and Find Full Text PDF