Dataset Information

Purkinje cell NMDA receptors assume a key role in synaptic gain control in the mature cerebellum.

ABSTRACT: A classic view in cerebellar physiology holds that Purkinje cells do not express functional NMDA receptors and that, therefore, postsynaptic NMDA receptors are not involved in the induction of long-term depression (LTD) at parallel fiber (PF) to Purkinje cell synapses. Recently, it has been demonstrated that functional NMDA receptors are postsynaptically expressed at climbing fiber (CF) to Purkinje cell synapses in mice, reaching full expression levels at ?2 months after birth. Here, we show that in the mature mouse cerebellum LTD (induced by paired PF and CF activation), but not long-term potentiation (LTP; PF stimulation alone) at PF to Purkinje cell synapses is blocked by bath application of the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid (D-APV). A blockade of LTD, but not LTP, was also observed when the noncompetitive NMDA channel blocker MK-801 was added to the patch-pipette saline, suggesting that postsynaptically expressed NMDA receptors are required for LTD induction. Using confocal calcium imaging, we show that CF-evoked calcium transients in dendritic spines are reduced in the presence of D-APV. This observation confirms that NMDA receptor signaling occurs at CF synapses and suggests that NMDA receptor-mediated calcium transients at the CF input site might contribute to LTD induction. Finally, we performed dendritic patch-clamp recordings from rat Purkinje cells. Dendritically recorded CF responses were reduced when D-APV was bath applied. Together, these data suggest that the late developmental expression of postsynaptic NMDA receptors at CF synapses onto Purkinje cells is associated with a switch toward an NMDA receptor-dependent LTD induction mechanism.

SUBMITTER: Piochon C

PROVIDER: S-EPMC2990192 | biostudies-other | 2010 Nov

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Purkinje cell NMDA receptors assume a key role in synaptic gain control in the mature cerebellum.

Piochon Claire C Levenes Carole C Ohtsuki Gen G Hansel Christian C

The Journal of neuroscience : the official journal of the Society for Neuroscience 20101101 45

A classic view in cerebellar physiology holds that Purkinje cells do not express functional NMDA receptors and that, therefore, postsynaptic NMDA receptors are not involved in the induction of long-term depression (LTD) at parallel fiber (PF) to Purkinje cell synapses. Recently, it has been demonstrated that functional NMDA receptors are postsynaptically expressed at climbing fiber (CF) to Purkinje cell synapses in mice, reaching full expression levels at ∼2 months after birth. Here, we show tha ...[more]

PMID: 21068337

Similar Datasets

Project description:UnlabelledThe basal ganglia (BG) control action selection, motor programs, habits, and goal-directed learning. The striatum, the principal input structure of BG, is predominantly composed of medium-sized spiny neurons (MSNs). Arising from these spatially intermixed MSNs, two inhibitory outputs form two main efferent pathways, the direct and indirect pathways. Striatonigral MSNs give rise to the activating, direct pathway MSNs and striatopallidal MSNs to the inhibitory, indirect pathway (iMSNs). BG output nuclei integrate information from both pathways to fine-tune motor procedures and to acquire complex habits and skills. Therefore, balanced activity between both pathways is crucial for harmonious functions of the BG. Despite the increase in knowledge concerning the role of glutamate NMDA receptors (NMDA-Rs) in the striatum, understanding of the specific functions of NMDA-R iMSNs is still lacking. For this purpose, we generated a conditional knock-out mouse to address the functions of the NMDA-R in the indirect pathway. At the cellular level, deletion of GluN1 in iMSNs leads to a reduction in the number and strength of the excitatory corticostriatopallidal synapses. The subsequent scaling down in input integration leads to dysfunctional changes in BG output, which is seen as reduced habituation, delay in goal-directed learning, lack of associative behavior, and impairment in action selection or skill learning. The NMDA-R deletion in iMSNs causes a decrease in the synaptic strength of striatopallidal neurons, which in turn might lead to a imbalanced integration between direct and indirect MSN pathways, making mice less sensitive to environmental change. Therefore, their ability to learn and adapt to the environment-based experience was significantly affected.Significance statementThe striatum controls habits, locomotion, and goal-directed behaviors by coordinated activation of two antagonistic pathways. Insofar as NMDA receptors (NMDA-Rs) play a key role in synaptic plasticity essential for sustaining these behaviors, we generated a mouse model lacking NMDA-Rs specifically in striatopallidal neurons. To our knowledge, this is the first time that a specific deletion of inhibitory, indirect pathway medium-sized spiny neuron (iMSN) NMDA-Rs has been used to address the role of these receptors in the inhibitory pathway. Importantly, we found that this specific deletion led to a significant reduction in the number and strength of the cortico-iMSN synapses, which resulted in the significant impairments of behaviors orchestrated by the basal ganglia. Our findings indicate that the NMDA-Rs of the indirect pathway are essential for habituation, action selection, and goal-directed learning.

Dataset Information

Purkinje cell NMDA receptors assume a key role in synaptic gain control in the mature cerebellum.

Publications

Purkinje cell NMDA receptors assume a key role in synaptic gain control in the mature cerebellum.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets