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Miniaturized Technologies for Enhancement of Motor Plasticity.

Moorjani S - Front Bioeng Biotechnol (2016)

Bottom Line: The idea that the damaged brain can functionally reorganize itself - so when one part fails, there lies the possibility for another to substitute - is an exciting discovery of the twentieth century.This is a very significant alteration from our previously static view of the brain and has profound implications for the rescue of function after a motor injury.Presentation of the right cues, applied in relevant spatiotemporal geometries, is required to awaken the dormant plastic forces essential for repair.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Biophysics, and the Washington National Primate Research Center, University of Washington , Seattle, WA , USA.

ABSTRACT
The idea that the damaged brain can functionally reorganize itself - so when one part fails, there lies the possibility for another to substitute - is an exciting discovery of the twentieth century. We now know that motor circuits once presumed to be hardwired are not, and motor-skill learning, exercise, and even mental rehearsal of motor tasks can turn genes on or off to shape brain architecture, function, and, consequently, behavior. This is a very significant alteration from our previously static view of the brain and has profound implications for the rescue of function after a motor injury. Presentation of the right cues, applied in relevant spatiotemporal geometries, is required to awaken the dormant plastic forces essential for repair. The focus of this review is to highlight some of the recent progress in neural interfaces designed to harness motor plasticity, and the role of miniaturization in development of strategies that engage diverse elements of the neuronal machinery to synergistically facilitate recovery of function after motor damage.

No MeSH data available.


Related in: MedlinePlus

Optical erasure of acquired motor learning. (A) Schematic illustrating the experiment performed by Kasai and coworkers (Hayashi-Takagi et al., 2015). When a mouse learns a new motor task, such as running on a rotating rod (called a rotarod), dendritic spines involved in learning this task become potentiated, i.e., there is formation of new spines and enlargement of existing ones, shown here in green. To necessitate the role of spines in motor learning, an optogenetic construct based on a photoactivatable form of the small signaling protein Rac1 was targeted to newly potentiated spines. Activation of the modified Rac1 construct with blue light induced shrinkage (or elimination) of learning-evoked spines, which caused the mouse to forget the skill it had acquired, so it soon fell off the rotarod. (B) Experimental setup. Spine shrinkage was optogenetically induced with light pulses delivered through bilateral optical fibres placed onto cranial windows created over the primary motor cortex. Drilled cranial holes were covered with glass coverslips, sealed with dental cement, followed by placement of the optical fibres for in vivo photoactivation (in freely moving animals), and attachment of the headgear for in vivo two-photon imaging. (C) Spines were labeled with Discosoma sp. red fluorescent protein (DsRed). Photoactivation induced selective shrinkage of spines containing AS-PaRac1, a light-sensitive probe that specifically labels newly potentiated spines. (D) Spine volume (V) following low-frequency pulsed activation. Dark green circles represent eliminated spines. (E) Photoactivation disrupted acquired learning in the rotarod performance of the AS-PaRac1 group, while the control mice were not affected, when it was performed immediately (i.e., 0 day) post training (Protocol 1). Photoactivation disrupted the acquired learning even one day post training (Protocol 2), when the majority of learning-evoked spines contained AS-PaRac1. By contrast, the photoactivation treatment two days post training (Protocol 3) failed to disrupt acquired learning even though a comparable number of spines contained AS-PaRac1 in protocols 2 and 3, suggesting that the learning-evoked spine potentiation visualized by AS-PaRac1 (at +1 day), but not spontaneous potentiation (at +2 days), accounted for the cortical-memory traces. Gray lines indicate individual task performance. Error bars represent standard error of the mean. Asterisks denote significant differences between compared groups. Scale bar in (C), 5 μm. NS, not significant; PA, photoactivation; AS, AS-PaRac1. Image adapted, with permission, from Hayashi-Takagi et al. (2015) and Lu and Zuo (2015).
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Figure 4: Optical erasure of acquired motor learning. (A) Schematic illustrating the experiment performed by Kasai and coworkers (Hayashi-Takagi et al., 2015). When a mouse learns a new motor task, such as running on a rotating rod (called a rotarod), dendritic spines involved in learning this task become potentiated, i.e., there is formation of new spines and enlargement of existing ones, shown here in green. To necessitate the role of spines in motor learning, an optogenetic construct based on a photoactivatable form of the small signaling protein Rac1 was targeted to newly potentiated spines. Activation of the modified Rac1 construct with blue light induced shrinkage (or elimination) of learning-evoked spines, which caused the mouse to forget the skill it had acquired, so it soon fell off the rotarod. (B) Experimental setup. Spine shrinkage was optogenetically induced with light pulses delivered through bilateral optical fibres placed onto cranial windows created over the primary motor cortex. Drilled cranial holes were covered with glass coverslips, sealed with dental cement, followed by placement of the optical fibres for in vivo photoactivation (in freely moving animals), and attachment of the headgear for in vivo two-photon imaging. (C) Spines were labeled with Discosoma sp. red fluorescent protein (DsRed). Photoactivation induced selective shrinkage of spines containing AS-PaRac1, a light-sensitive probe that specifically labels newly potentiated spines. (D) Spine volume (V) following low-frequency pulsed activation. Dark green circles represent eliminated spines. (E) Photoactivation disrupted acquired learning in the rotarod performance of the AS-PaRac1 group, while the control mice were not affected, when it was performed immediately (i.e., 0 day) post training (Protocol 1). Photoactivation disrupted the acquired learning even one day post training (Protocol 2), when the majority of learning-evoked spines contained AS-PaRac1. By contrast, the photoactivation treatment two days post training (Protocol 3) failed to disrupt acquired learning even though a comparable number of spines contained AS-PaRac1 in protocols 2 and 3, suggesting that the learning-evoked spine potentiation visualized by AS-PaRac1 (at +1 day), but not spontaneous potentiation (at +2 days), accounted for the cortical-memory traces. Gray lines indicate individual task performance. Error bars represent standard error of the mean. Asterisks denote significant differences between compared groups. Scale bar in (C), 5 μm. NS, not significant; PA, photoactivation; AS, AS-PaRac1. Image adapted, with permission, from Hayashi-Takagi et al. (2015) and Lu and Zuo (2015).

Mentions: Indeed, an exciting recent study combined two-photon imaging, optogenetics, and in vivo photoactivation in freely moving mice to elucidate the crucial role of dendritic spines in representation of motor-memory traces. Kasai and colleagues abolished motor learning by selective optical shrinkage of ­learning-evoked spines, showing that a newly acquired motor skill depends on the formation of task-specific synaptic ensembles (Figure 4; Hayashi-Takagi et al., 2015), and demonstrating the power of optical technologies for correlating synaptic-plasticity mechanisms with observed behavior.


Miniaturized Technologies for Enhancement of Motor Plasticity.

Moorjani S - Front Bioeng Biotechnol (2016)

Optical erasure of acquired motor learning. (A) Schematic illustrating the experiment performed by Kasai and coworkers (Hayashi-Takagi et al., 2015). When a mouse learns a new motor task, such as running on a rotating rod (called a rotarod), dendritic spines involved in learning this task become potentiated, i.e., there is formation of new spines and enlargement of existing ones, shown here in green. To necessitate the role of spines in motor learning, an optogenetic construct based on a photoactivatable form of the small signaling protein Rac1 was targeted to newly potentiated spines. Activation of the modified Rac1 construct with blue light induced shrinkage (or elimination) of learning-evoked spines, which caused the mouse to forget the skill it had acquired, so it soon fell off the rotarod. (B) Experimental setup. Spine shrinkage was optogenetically induced with light pulses delivered through bilateral optical fibres placed onto cranial windows created over the primary motor cortex. Drilled cranial holes were covered with glass coverslips, sealed with dental cement, followed by placement of the optical fibres for in vivo photoactivation (in freely moving animals), and attachment of the headgear for in vivo two-photon imaging. (C) Spines were labeled with Discosoma sp. red fluorescent protein (DsRed). Photoactivation induced selective shrinkage of spines containing AS-PaRac1, a light-sensitive probe that specifically labels newly potentiated spines. (D) Spine volume (V) following low-frequency pulsed activation. Dark green circles represent eliminated spines. (E) Photoactivation disrupted acquired learning in the rotarod performance of the AS-PaRac1 group, while the control mice were not affected, when it was performed immediately (i.e., 0 day) post training (Protocol 1). Photoactivation disrupted the acquired learning even one day post training (Protocol 2), when the majority of learning-evoked spines contained AS-PaRac1. By contrast, the photoactivation treatment two days post training (Protocol 3) failed to disrupt acquired learning even though a comparable number of spines contained AS-PaRac1 in protocols 2 and 3, suggesting that the learning-evoked spine potentiation visualized by AS-PaRac1 (at +1 day), but not spontaneous potentiation (at +2 days), accounted for the cortical-memory traces. Gray lines indicate individual task performance. Error bars represent standard error of the mean. Asterisks denote significant differences between compared groups. Scale bar in (C), 5 μm. NS, not significant; PA, photoactivation; AS, AS-PaRac1. Image adapted, with permission, from Hayashi-Takagi et al. (2015) and Lu and Zuo (2015).
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Figure 4: Optical erasure of acquired motor learning. (A) Schematic illustrating the experiment performed by Kasai and coworkers (Hayashi-Takagi et al., 2015). When a mouse learns a new motor task, such as running on a rotating rod (called a rotarod), dendritic spines involved in learning this task become potentiated, i.e., there is formation of new spines and enlargement of existing ones, shown here in green. To necessitate the role of spines in motor learning, an optogenetic construct based on a photoactivatable form of the small signaling protein Rac1 was targeted to newly potentiated spines. Activation of the modified Rac1 construct with blue light induced shrinkage (or elimination) of learning-evoked spines, which caused the mouse to forget the skill it had acquired, so it soon fell off the rotarod. (B) Experimental setup. Spine shrinkage was optogenetically induced with light pulses delivered through bilateral optical fibres placed onto cranial windows created over the primary motor cortex. Drilled cranial holes were covered with glass coverslips, sealed with dental cement, followed by placement of the optical fibres for in vivo photoactivation (in freely moving animals), and attachment of the headgear for in vivo two-photon imaging. (C) Spines were labeled with Discosoma sp. red fluorescent protein (DsRed). Photoactivation induced selective shrinkage of spines containing AS-PaRac1, a light-sensitive probe that specifically labels newly potentiated spines. (D) Spine volume (V) following low-frequency pulsed activation. Dark green circles represent eliminated spines. (E) Photoactivation disrupted acquired learning in the rotarod performance of the AS-PaRac1 group, while the control mice were not affected, when it was performed immediately (i.e., 0 day) post training (Protocol 1). Photoactivation disrupted the acquired learning even one day post training (Protocol 2), when the majority of learning-evoked spines contained AS-PaRac1. By contrast, the photoactivation treatment two days post training (Protocol 3) failed to disrupt acquired learning even though a comparable number of spines contained AS-PaRac1 in protocols 2 and 3, suggesting that the learning-evoked spine potentiation visualized by AS-PaRac1 (at +1 day), but not spontaneous potentiation (at +2 days), accounted for the cortical-memory traces. Gray lines indicate individual task performance. Error bars represent standard error of the mean. Asterisks denote significant differences between compared groups. Scale bar in (C), 5 μm. NS, not significant; PA, photoactivation; AS, AS-PaRac1. Image adapted, with permission, from Hayashi-Takagi et al. (2015) and Lu and Zuo (2015).
Mentions: Indeed, an exciting recent study combined two-photon imaging, optogenetics, and in vivo photoactivation in freely moving mice to elucidate the crucial role of dendritic spines in representation of motor-memory traces. Kasai and colleagues abolished motor learning by selective optical shrinkage of ­learning-evoked spines, showing that a newly acquired motor skill depends on the formation of task-specific synaptic ensembles (Figure 4; Hayashi-Takagi et al., 2015), and demonstrating the power of optical technologies for correlating synaptic-plasticity mechanisms with observed behavior.

Bottom Line: The idea that the damaged brain can functionally reorganize itself - so when one part fails, there lies the possibility for another to substitute - is an exciting discovery of the twentieth century.This is a very significant alteration from our previously static view of the brain and has profound implications for the rescue of function after a motor injury.Presentation of the right cues, applied in relevant spatiotemporal geometries, is required to awaken the dormant plastic forces essential for repair.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Biophysics, and the Washington National Primate Research Center, University of Washington , Seattle, WA , USA.

ABSTRACT
The idea that the damaged brain can functionally reorganize itself - so when one part fails, there lies the possibility for another to substitute - is an exciting discovery of the twentieth century. We now know that motor circuits once presumed to be hardwired are not, and motor-skill learning, exercise, and even mental rehearsal of motor tasks can turn genes on or off to shape brain architecture, function, and, consequently, behavior. This is a very significant alteration from our previously static view of the brain and has profound implications for the rescue of function after a motor injury. Presentation of the right cues, applied in relevant spatiotemporal geometries, is required to awaken the dormant plastic forces essential for repair. The focus of this review is to highlight some of the recent progress in neural interfaces designed to harness motor plasticity, and the role of miniaturization in development of strategies that engage diverse elements of the neuronal machinery to synergistically facilitate recovery of function after motor damage.

No MeSH data available.


Related in: MedlinePlus