Role of motor cortex NMDA receptors in learning-dependent synaptic plasticity of behaving mice

Mazahir T. Hasan (), Samuel Hernández-González, Godwin Dogbevia, Mario Treviño, Ilaria Bertocchi, Agnès Gruart and José M. Delgado-García ()
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Mazahir T. Hasan: Max Planck Institute for Medical Research
Samuel Hernández-González: University Pablo de Olavide
Godwin Dogbevia: Max Planck Institute for Medical Research
Mario Treviño: Max Planck Institute for Medical Research
Ilaria Bertocchi: Max Planck Institute for Medical Research
Agnès Gruart: University Pablo de Olavide
José M. Delgado-García: University Pablo de Olavide

Nature Communications, 2013, vol. 4, issue 1, 1-10

Abstract: Abstract The primary motor cortex has an important role in the precise execution of learned motor responses. During motor learning, synaptic efficacy between sensory and primary motor cortical neurons is enhanced, possibly involving long-term potentiation and N-methyl-D-aspartate (NMDA)-specific glutamate receptor function. To investigate whether NMDA receptor in the primary motor cortex can act as a coincidence detector for activity-dependent changes in synaptic strength and associative learning, here we generate mice with deletion of the Grin1 gene, encoding the essential NMDA receptor subunit 1 (GluN1), specifically in the primary motor cortex. The loss of NMDA receptor function impairs primary motor cortex long-term potentiation in vivo. Importantly, it impairs the synaptic efficacy between the primary somatosensory and primary motor cortices and significantly reduces classically conditioned eyeblink responses. Furthermore, compared with wild-type littermates, mice lacking NMDA receptors in the primary motor cortex show slower learning in Skinner-box tasks. Thus, primary motor cortex NMDA receptors are necessary for activity-dependent synaptic strengthening and associative learning.

Date: 2013
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DOI: 10.1038/ncomms3258

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