NMDARs contribute to the facial stimuli-evoked mossy fiber-granule cell synaptic transmission in vivo in mice

Zhang, Mengjie; Zhang, Guangjian; Li, Bingxue; Bing, Yan-Hua; Cui, Bai-Ri; Cui, Lina; Chu, Chun-Ping; Qiu, De-Lai

doi:10.1016/j.neulet.2020.135285

Cited by 7 publications

(24 citation statements)

References 25 publications

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“…Previous studies demonstrated that chronic ethanol exposure overdose impairs neuronal function via NMDARs ( Nagy, 2004 ) and that NMDARs contribute to the later components of facial stimulation evoked by MF–GC synaptic transmission in the mouse cerebellar GL ( Zhang et al, 2020 ). We examined the effect of adolescent chronic ethanol exposure on the NMDARs-mediated components of facial stimulation-evoked MF–GC synaptic transmission.…”

Section: Resultsmentioning

confidence: 99%

“…We examined the effect of adolescent chronic ethanol exposure on the NMDARs-mediated components of facial stimulation-evoked MF–GC synaptic transmission. To activate NMDARs in the cerebellar GL during facial stimulation-evoked MF–GC synaptic transmission, we employed a facial stimuli train (20 Hz, five pulses) to evoke five field potential responses (N1–N5) in the cerebellar GL ( Zhang et al, 2020 ). Application of the selective NMDAR antagonist D-APV (250 μM) did not significantly affect the amplitude of N1 but induced a decrease in the amplitudes of N2–N5 in both the control ( P < 0.05 vs. ACSF; Figures 2A,B ) and the chronic ethanol-exposed mice ( P < 0.05 vs. ACSF; Figures 2A,C ).…”

Section: Resultsmentioning

confidence: 99%

“…GluN2A is expressed on the somas of GCs and the boutons of parallel fibers ( Glitsch and Marty, 1999 ; Casado et al, 2000 ) and contributes to the facial stimulation-evoked MF–GC synaptic transmission in mice in vivo ( Zhang et al, 2020 ). We observed the effect of a GluN2A blocker, PEAQX (10 μM), on the facial stimulation-evoked MF–GC synaptic transmission in the cerebellar GL of mice.…”

Section: Resultsmentioning

confidence: 99%

“…In a previous study, NR2A and NR2C mRNA were detected in cerebellar GCs during the second postnatal week, whereas the NR2B mRNA was transiently expressed in the GCs during the first 2 postnatal weeks in rats ( Akazawa et al, 1994 ). GluN2A has been detected on the somas of the GCs and boutons of the parallel fibers ( Glitsch and Marty, 1999 ; Casado et al, 2000 ) and contributes to facial stimulation-evoked MF–GC synaptic transmission in mice in vivo ( Zhang et al, 2020 ). It has been demonstrated that the GluN2C subunit was preferentially incorporated into triheteromeric GluN1/GluN2A/GluN2C receptors in cerebellar GCs, which might contribute to MF–GC synaptic transmission ( Bhattacharya et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

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Chronic Ethanol Exposure Enhances Facial Stimulation-Evoked Mossy Fiber–Granule Cell Synaptic Transmission via GluN2A Receptors in the Mouse Cerebellar Cortex

GuangHui

et al. 2021

Front. Syst. Neurosci.

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Sensory information is transferred to the cerebellar cortex via 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 in vivo. 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. Chronic ethanol exposure from adolescence induced an enhancement of facial stimulation-evoked MF–GC synaptic transmission in the cerebellar cortex of adult mice. The application of an N-methyl-D-aspartate receptor (NMDAR) antagonist, D-APV (250 μM), induced stronger depression of facial stimulation-evoked MF–GC synaptic transmission in chronic ethanol-exposed mice compared with that in control mice. Chronic ethanol exposure-induced facilitation of facial stimulation evoked by MF–GC synaptic transmission was abolished by a selective GluN2A antagonist, PEAQX (10 μM), but was unaffected by the application of a selective GluN2B antagonist, TCN-237 (10 μM), or a type 1 metabotropic glutamate receptor blocker, JNJ16259685 (10 μM). These results indicate that chronic ethanol exposure from adolescence enhances facial stimulation-evoked MF–GC synaptic transmission via GluN2A, which suggests that chronic ethanol exposure from adolescence impairs the high-fidelity transmission capability of sensory information in the cerebellar cortex by enhancing the NMDAR-mediated components of MF–GC synaptic transmission in adult mice in vivo.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Chronic Ethanol Exposure Enhances Facial Stimulation-Evoked Mossy Fiber–Granule Cell Synaptic Transmission via GluN2A Receptors in the Mouse Cerebellar Cortex

GuangHui

et al. 2021

Front. Syst. Neurosci.

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“…Besides, increased NMDAR-EPSCs facilitated spiking of GluA4-KO GCs during high-frequency synaptic input. Compared with slice recordings, the contribution of NMDARs to GC synaptic excitation is likely to be larger in vivo ( Zhang et al, 2020 ), due to the more depolarized membrane potential and increased spontaneous input in GCs. The larger NMDAR-EPSCs in GluA4-KO are most likely caused by enhanced glutamate release ( Chourbaji et al, 2008 ; Delvendahl et al, 2019 ) that is driven by an increase in the number of presynaptic release sites, but we cannot exclude postsynaptic contributions.…”

Section: Discussionmentioning

confidence: 99%

GluA4 facilitates cerebellar expansion coding and enables associative memory formation

Kita

Albergaria

Machado

et al. 2021

eLife

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AMPA receptors (AMPARs) mediate excitatory neurotransmission in the CNS and their subunit composition determines synaptic efficacy. Whereas AMPAR subunits GluA1–GluA3 have been linked to particular forms of synaptic plasticity and learning, the functional role of GluA4 remains elusive. Here we demonstrate a crucial function of GluA4 for synaptic excitation and associative memory formation in the cerebellum. Notably, GluA4-knockout mice had ~80% reduced mossy fiber to granule cell synaptic transmission. The fidelity of granule cell spike output was markedly decreased despite attenuated tonic inhibition and increased NMDA receptor-mediated transmission. Computational network modeling incorporating these changes revealed that deletion of GluA4 impairs granule cell expansion coding, which is important for pattern separation and associative learning. On a behavioral level, while locomotor coordination was generally spared, GluA4-knockout mice failed to form associative memories during delay eyeblink conditioning. These results demonstrate an essential role for GluA4-containing AMPARs in cerebellar information processing and associative learning.

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Gestational valproic acid exposure enhances facial stimulation-evoked cerebellar mossy fiber-granule cell transmission via GluN2A subunit-containing NMDA receptor in offspring mice

Yuan,

Liu,

Zhang

et al. 2024

Transl Psychiatry

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Valproic 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. Three-chamber testing showed that mice exposed to VPA mice exhibited a significant reduction in social interaction compared with the control group. In vivo electrophysiological recordings revealed that a pair of air-puff stimulation on ipsilateral whisker pad evoked MF-GC synaptic transmission, N1, and N2. The evoked MF-GC synaptic responses in VPA-exposed mice exhibited a significant increase in the area under the curve (AUC) of N1 and the amplitude and AUC of N2 compared with untreated mice. Cerebellar surface application of the selective N-methyl-D-aspartate (NMDA) receptor blocker D-APV significantly inhibited facial stimulation-evoked MF-GC synaptic transmission. In the presence of D-APV, there were no significant differences between the AUC of N1 and the amplitude and AUC of N2 in the VPA-exposed mice and those of the untreated mice. Notably, blockade of the GluN2A subunit-containing, but not the GluN2B subunit-containing, NMDA receptor, significantly inhibited MF-GC synaptic transmission and decreased the AUC of N1 and the amplitude and AUC of N2 in VPA-exposed mice to levels similar to those seen in untreated mice. In addition, the GluN2A subunit-containing NMDA receptor was expressed at higher levels in the GC layer of VPA-treated mice than in control mice. These results indicate that gestational VPA exposure in mice produces ASD-like behaviors, accompanied by increased cerebellar MF-GC synaptic transmission and an increase in GluN2A subunit-containing NMDA receptor expression in the offspring.

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NMDARs contribute to the facial stimuli-evoked mossy fiber-granule cell synaptic transmission in vivo in mice

Cited by 7 publications

References 25 publications

Chronic Ethanol Exposure Enhances Facial Stimulation-Evoked Mossy Fiber–Granule Cell Synaptic Transmission via GluN2A Receptors in the Mouse Cerebellar Cortex

Chronic Ethanol Exposure Enhances Facial Stimulation-Evoked Mossy Fiber–Granule Cell Synaptic Transmission via GluN2A Receptors in the Mouse Cerebellar Cortex

GluA4 facilitates cerebellar expansion coding and enables associative memory formation

Gestational valproic acid exposure enhances facial stimulation-evoked cerebellar mossy fiber-granule cell transmission via GluN2A subunit-containing NMDA receptor in offspring mice

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