Enhancing motor learning by increasing the stability of newly formed dendritic spines in the motor cortex

Albarran, Eddy; Raissi, Aram; Jáidar, Omar; Shatz, Carla J.; Ding, Jun

doi:10.1016/j.neuron.2021.07.030

Cited by 35 publications

(31 citation statements)

References 86 publications

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“…Similarly, behavior-relevant neurons that we labeled using the genetic TRAP approach become increasingly reactivated with enhanced motor performance of trained mice, suggesting that well-trained mice reactivate the same subset of M1 neurons during individual reaching sessions, whereas naïve or non-learner mice use a different subset of neurons in each session (Figure 1). This enhanced reactivation also coincides with the timeline in which individual reaching attempts become more stereotyped with reduced variability (Albarran et al, 2021). Together, these findings support the concept that neurons with behavior-related activity patterns form a motor memory engram, which becomes more defined with persistent learning.…”

Section: Discussionsupporting

confidence: 76%

“…Newly formed spines are also selectively stabilized during learning, where increased levels of new spine survival correlate with behavioral performance (Albarran et al, 2021). Therefore, we assessed the survival of spines that were newly formed during the first two days of training and found that spine survival is indeed significantly higher in TRAP dendrites of trained mice compared to non-TRAP dendrites, a difference that persisted for at least a week after training (Figure 2H).…”

Section: M1 Dendritic Spine Plasticity Is Specific To Motor Engram Neuronsmentioning

confidence: 97%

“…However, whether these neurons that are activated during motor learning are reactivated during the performance of a previously learned motor task has not been tested. To label motor behavioractivated neurons in M1 during motor learning, we trained c-fos TRAP mice to perform a forelimb reaching task, in which mice use a single paw to reach for a small food pellet through a slit opening in the training chamber (Figure 1A) (Xu et al, 2009;Guo et al, 2015;Roth et al, 2020;Albarran et al, 2021). Over the course of eight days of daily training, mice increased their rate of successfully retrieving the pellet (Figure 1B).…”

Section: M1 Engram Neurons Are Reactivated When Performing a Learned Motor Taskmentioning

confidence: 99%

“…In the motor cortex, synaptic plasticity on dendrites of Layer 5 pyramidal neurons (L5PNs) play a crucial role in the acquisition of new motor skills (Rioult-Pedotti et al, 2000;Xu et al, 2009;Yang et al, 2009;Guo et al, 2015;Roth et al, 2020;Albarran et al, 2021). Specifically, motor learning induces enhanced formation of new dendritic spines and a delayed increase in spine elimination, which results in a transient increase in spine density on L5PNs.…”

Section: Introductionmentioning

confidence: 99%

“…Specifically, motor learning induces enhanced formation of new dendritic spines and a delayed increase in spine elimination, which results in a transient increase in spine density on L5PNs. The rate of spine formation and especially the stabilization of newly formed spines correlates with motor performance (Xu et al, 2009;Albarran et al, 2021). Furthermore, artificially eliminating learninginduced new spines impairs learned motor behaviors (Hayashi-Takagi et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Motor learning selectively strengthens cortical and striatal synapses of motor engram neurons

Hwang

Roth

et al. 2021

Preprint

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SUMMARYLearning and consolidation of new motor skills require adaptations of neuronal activity and connectivity in the motor cortex and striatum, two key motor regions of the brain. Yet, how neurons undergo synaptic changes and become recruited during motor learning to form a memory engram remains an open question. Here, we train mice on a single-pellet reaching motor learning task and use a genetic approach to identify and manipulate behavior-relevant neurons selectively in the primary motor cortex (M1). We find that the degree of reactivation of M1 engram neurons correlates strongly with motor performance. We further demonstrate that learning-induced dendritic spine reorganization specifically occurs in these M1 engram neurons. In addition, we find that motor learning leads to an increase in the number and strength of outputs from M1 engram neurons onto striatal spiny projection neurons (SPNs) and that these synapses form local clusters along SPN dendrites. These results identify a highly specific synaptic plasticity during the formation of long-lasting motor memory traces in the corticostriatal circuit.HIGHLIGHTS– Motor performance is correlated with the reactivation of motor engram neurons– Motor learning increases spine density and new spine survival selectively on M1 engram neurons– Motor learning strengthens motor engram outputs to the striatum– M1 engram outputs converge onto clusters of dendritic spines on striatal spiny projection neurons

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Section: Discussionsupporting

confidence: 76%

Section: M1 Dendritic Spine Plasticity Is Specific To Motor Engram Neuronsmentioning

confidence: 97%

Section: M1 Engram Neurons Are Reactivated When Performing a Learned Motor Taskmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Motor learning selectively strengthens cortical and striatal synapses of motor engram neurons

Hwang

Roth

et al. 2021

Preprint

Self Cite

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Dendritic Spines in Learning and Memory: From First Discoveries to Current Insights

Heck,

Santos

2023

Advances in Neurobiology

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Involvement of Paired Immunoglobulin-Like Receptor B in Cognitive Dysfunction Through Hippocampal-Dependent Synaptic Plasticity Impairments in Mice Subjected to Chronic Sleep Restriction

Zhai

Gou

et al. 2022

Mol Neurobiol

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Sleep loss is often associated with cognitive dysfunction. Alterations in the structure and function of synapses in the hippocampus are thought to underlie memory storage. Paired immunoglobulin-like receptor B (PirB) plays a negative role in various neurological diseases by inhibiting axon regeneration and synaptic plasticity. However, the contributions of PirB to the mechanisms underlying the changes in synaptic plasticity after sleep loss that ultimately promote deficits in cognitive function have not been well elucidated. Here, we showed that chronic sleep restriction (CSR) mice displayed cognitive impairment and synaptic deficits accompanied by upregulation of PirB expression in the hippocampus. Mechanistically, PirB caused the dysregulation of actin through the RhoA/ROCK2/LIMK1/cofilin signalling pathway, leading to abnormal structural and functional plasticity, which in turn resulted in cognitive dysfunction. PirB knockdown alleviated synaptic deficits and cognitive impairment after CSR by inhibiting the RhoA/ROCK2/LIMK1/cofilin signalling pathway. Moreover, we found that fasudil, a widely used ROCK2 inhibitor, could mimic the beneficial effect of PirB knockdown and ameliorate synaptic deficits and cognitive impairment, further demonstrating that PirB induced cognitive dysfunction after CSR via the RhoA/ROCK2/LIMK1/cofilin signalling pathway. Our study sheds new light on the role of PirB as an important mediator in modulating the dysfunction of synaptic plasticity and cognitive function via the RhoA/ROCK2/LIMK1/cofilin signalling pathway, which indicated that hippocampal PirB is a promising therapeutic target for counteracting cognitive impairment after CSR. Graphical Abstract This illustration depicts the signalling pathway by PirB in mediating cognitive impairment and synaptic deficits in CSR mice. In the hippocampus of CSR mice, the expression level of PirB was significantly increased. In addition, CSR increases RhoA and ROCK2 levels and reduces levels of both LIMK1 and cofilin phosphorylation. PirB knockdown reverses cognitive impairment and synaptic plasticity disorders caused by CSR through the RhoA/ROCK2/LIMK1/cofilin signalling pathway

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Enhancing motor learning by increasing the stability of newly formed dendritic spines in the motor cortex

Cited by 35 publications

References 86 publications

Motor learning selectively strengthens cortical and striatal synapses of motor engram neurons

Motor learning selectively strengthens cortical and striatal synapses of motor engram neurons

Dendritic Spines in Learning and Memory: From First Discoveries to Current Insights

Involvement of Paired Immunoglobulin-Like Receptor B in Cognitive Dysfunction Through Hippocampal-Dependent Synaptic Plasticity Impairments in Mice Subjected to Chronic Sleep Restriction

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