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

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 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.

Higher brain functions served by the lowly rodent primary visual cortex

“…For example, the interval timing work follows earlier findings that the response properties of S1 neurons change according to whether whisker stimulation occurs in the context of passive or active tactile stimulation (Krupa et al 2004). Context-and experiencedependent modifications of the auditory cortex have been particularly well characterized (Weinberger 2004(Weinberger , 2011, the olfactory cortex can acquire associative threat representations (Li 2014), and NMDA receptor-dependent associative learning even occurs within the primary motor cortex (Hasan et al 2013). Recent results showing that rodents can volitionally generate specific neural activity patterns in S1 in order to receive reward (Clancy et al 2014) further support the idea that primary sensory areas are capable of more than simple feature extraction within their specific modality and can play an active role in behaviorally relevant cortical processing.…”

Fear Memory

“…It has been discussed whether parallel processing of the memory of eyeblink conditioning by structures as far apart as the hippocampus and the cerebellum is essential for the ultimate long-term storage of this behavior or merely reflects two relatively independent storage processes (226,230,293,557,669). Careful posttraining ablation experiments suggest that in the first day or two of multi-trial training both the hippocampus and the cerebellum together with the prefrontal cortex are required for eyeblink conditioning; at later times prefrontal areas also play a role, and if the training is prolonged for weeks, first the hippocampus and then the prefrontal cortex become gradually less important and the cerebellum assumes the pivotal role (622).…”

Hypothesis to Explain Yawning, Cortisol Rise, Brain Cooling and Motor Cortex Involvement of Involuntary Arm Movement in Neurologically Impaired Patients

“…The Gamma-aminobutyric acid (GABA)-beta receptors are often affected (Figure 3) [27] and particularly, they are influenced by the circulating cortisol levels [26]. Hasan and colleagues [28] found the motor cortex in mice has sophisticated receptors important in learned motor responses. During motor learning, they found synaptic efficacy is enhanced between sensory and primary motor cortisol neurons.…”