Motor Skill Learning Depends on Protein Synthesis in Motor Cortex after Training

Abstract

The role of protein synthesis in memory consolidation is well established for hippocampus-dependent learning and synaptic plasticity. Whether protein synthesis is required for motor skill learning is unknown. We hypothesized that skill learning is interrupted by protein synthesis inhibition (PSI). We intended to test whether local protein synthesis in motor cortex or cerebellum is required during skill acquisition and consolidation. Anisomycin (ANI; 100 g/l in 1 l of PBS) injected into motor cortex, posterior parietal cortex, or cerebellum produced 84.0 Ϯ 1.44% (mean Ϯ SEM), 85.9 Ϯ 2.31%, and 87.3 Ϯ 0.17% of PSI 60 min after administration, respectively. In motor cortex, protein synthesis was still reduced at 24 hr (72.0 Ϯ 4.68% PSI) but normalized at 48 hr after a second injection given 24 hr after the first. To test for the effects of PSI on learning of a skilled reaching task, ANI was injected into motor cortex contralateral to the trained limb or into ipsilateral cerebellum immediately after daily training sessions 1 and 2. Two control groups received motor cortex injections of vehicle or ANI injections into contralateral parietal cortex. Control and cerebellar animals showed a sigmoid learning curve, which plateaued after day 4. PSI in motor cortex significantly reduced learning during days 1-4. Thereafter, when protein synthesis normalized, learning was reinitiated. ANI injections into motor cortex did not induce a motor deficit, because animals injected during the performance plateau did not deteriorate. This demonstrates that motor skill learning depends on de novo synthesis of proteins in motor cortex after training.

Topography and collateralization of dopaminergic projections to primary motor cortex in rats

“…Recently, dopaminergic projections from midbrain to M1 have been shown to be a prerequisite for motor skill learning Hosp et al 2011). M1 is thought to be a key structure for the storage of the motor memory trace (Luft et al 2004;Monfils et al 2005) and dopaminergic signaling promotes plasticity in M1 circuitry at various levels (for review see also Hosp and Luft 2013): (1) at the network level, dopamine increases M1 excitability and integrity of motor maps (Hosp et al 2009), a prerequisite for successful motor learning (Conner et al 2003). (2) At the cellular level, dopamine induces the expression of c-Fos (Hosp et al 2011), a transcription factor related to motor learning (Kleim et al 1996).…”

Motor cortical stimulation promotes synaptic plasticity and behavioral improvements following sensorimotor cortex lesions

“…However, practice in skilled reaching improves post-lesion reaching deficits and reinstates motor maps Friel et al, 2000;Conner et al, 2005;Ramanathan et al, 2006). Disruption of motor cortical plasticity decreases reaching performance (Kleim et al, 2003a;Luft et al, 2004). In rats, injection of protein synthesis inhibitors within the motor cortex causes synapses to be lost, motor maps to disappear and reaching behavior to become impaired (Kleim et al, 2003a).…”

Biphasic plasticity of dendritic fields in layer V motor neurons in response to motor learning

“…Alternatively, motor learning may consist of several processes that follow each other, e.g. reflecting initial acquisition and short-term consolidation in between sessions [2] followed by long-term consolidation of the sequence of movement elements [19,20]. Long-term consolidation may account for the preservation of skills for years without use of the skill.…”

“…The primary motor cortex (M1) is involved in learning novel movement sequences, possibly as a site where the motor memory trace is formed [1,2]. In rodents that learn a motor task [3], plastic changes within M1 have been observed in the form of structural modification in dendrites [4] and their spines [5], in gene expression [6,7], synaptic weights [8] and motor maps [9].…”