Readily evoked forelimb movement in rat via optogenetic stimulation of motor cortex

Abstract INTRODUCTION Poststroke optogenetic stimulation has been shown to enhance neurovascular coupling and functional recovery. Neuronal nitric oxide synthase (nNOS) has been implicated as a key regulator of neurovascular response in acute stroke but its role in subacute recovery remains unclear. Here we investigate nNOS expression in stroke mice undergoing optogenetic stimulation of the contralesional lateral cerebellar nucleus (cLCN). We also examine the effects of nNOS inhibition on functional recovery using a pharmacological inhibitor targeting nNOS. METHODS Transgenic Thy1-ChR2-YFP male mice (10-12 wk) were used. Stereotaxic surgery was performed to implant a fiber cannula in the cLCN and animals underwent intraluminal middle cerebral artery suture occlusion (30 min). Optogenetic stimulation began at poststroke (PD) day 5 and continued until PD14. Sensorimotor tests were used to assess behavioral recovery at PD4, 7, 10, and 14. At PD15, primary motor cortex from both ipsi- and contralesional motor cortex (iM1, cM1) were dissected. nNOS mRNA and protein levels were examined using quantitative polymerase chain reaction and western blot. In another set of studies, nNOS inhibitor ARL 17477 dihydrochloride (10 mg/kg, intraperitoneally) was administered daily between PD5-14 and functional recovery was evaluated using sensorimotor tests. RESULTS cLCN stimulated stroke mice demonstrated significant improvement in speed (cm/s) on the rotating beam task at PD10 and 14 day (P < .05, P < .001 respectively). nNOS mRNA and protein expression was significantly and selectively decreased in cM1 of cLCN stimulated mice (P < .05). The reduced nNOS expression in cM1 was negatively correlated with improved recovery (R2 = −0.839, Pearson P = .009). nNOS inhibitor-treated stroke mice exhibited a significant functional improvement in speed at PD10, when compared to stroke mice receiving vehicle (saline) (P < .05). CONCLUSION Our results suggest that nNOS may play a maladaptive role in poststroke recovery. Optogenetic stimulation of cLCN and systemic nNOS inhibition produce functional benefits after stroke.

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Arm movements induced by noninvasive optogenetic stimulation of the motor cortex in the common marmoset

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1903445116 ◽

2019 ◽

Vol 116 (45) ◽

pp. 22844-22850 ◽

Cited By ~ 10

Author(s):

Teppei Ebina ◽

Keitaro Obara ◽

Akiya Watakabe ◽

Yoshito Masamizu ◽

Shin-Ichiro Terada ◽

...

Keyword(s):

Motor Cortex ◽

Nonhuman Primates ◽

Arm Movements ◽

Common Marmoset ◽

Blue Laser ◽

Optogenetic Stimulation ◽

Long Duration ◽

The Common ◽

Forelimb Movements ◽

Stimulation Of

Optogenetics is now a fundamental tool for investigating the relationship between neuronal activity and behavior. However, its application to the investigation of motor control systems in nonhuman primates is rather limited, because optogenetic stimulation of cortical neurons in nonhuman primates has failed to induce or modulate any hand/arm movements. Here, we used a tetracycline-inducible gene expression system carrying CaMKII promoter and the gene encoding a Channelrhodopsin-2 variant with fast kinetics in the common marmoset, a small New World monkey. In an awake state, forelimb movements could be induced when Channelrhodopsin-2−expressing neurons in the motor cortex were illuminated by blue laser light with a spot diameter of 1 mm or 2 mm through a cranial window without cortical invasion. Forelimb muscles responded 10 ms to 50 ms after photostimulation onset. Long-duration (500 ms) photostimulation induced discrete forelimb movements that could be markerlessly tracked with charge-coupled device cameras and a deep learning algorithm. Long-duration photostimulation mapping revealed that the primary motor cortex is divided into multiple domains that can induce hand and elbow movements in different directions. During performance of a forelimb movement task, movement trajectories were modulated by weak photostimulation, which did not induce visible forelimb movements at rest, around the onset of task-relevant movement. The modulation was biased toward the movement direction induced by the strong photostimulation. Combined with calcium imaging, all-optical interrogation of motor circuits should be possible in behaving marmosets.

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193 Optogenetic Stimulation of Motor Cortex Neurons Promotes Functional Recovery After Stroke

Neurosurgery ◽

10.1227/01.neu.0000432783.58847.ba ◽

2013 ◽

Vol 60 ◽

pp. 184

Author(s):

Michelle Cheng ◽

Wyatt J. Woodson ◽

Eric Wang ◽

Stephanie Wang ◽

GuoHua Sun ◽

...

Keyword(s):

Motor Cortex ◽

Functional Recovery ◽

Optogenetic Stimulation ◽

Stimulation Of

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Optogenetic stimulation of the motor cortex alleviates neuropathic pain in rats of infraorbital nerve injury with/without CGRP knock-down

10.21203/rs.3.rs-48555/v2 ◽

2020 ◽

Author(s):

Jaisan Islam ◽

Elina KC ◽

Byeong Ho Oh ◽

Soochong Kim ◽

Sang-hwan Hyun ◽

...

Keyword(s):

Neuropathic Pain ◽

Motor Cortex ◽

Trigeminal Neuralgia ◽

Trigeminal Ganglion ◽

Primary Motor Cortex ◽

Infraorbital Nerve ◽

Motor Cortex Stimulation ◽

Trigeminal Neuropathic Pain ◽

Optogenetic Stimulation ◽

Stimulation Of

Abstract Background Previous studies have reported that electrical stimulation of the motor cortex is effective in reducing trigeminal neuropathic pain; however, the effects of optical motor cortex stimulation remain unclear. Objective The present study aimed to investigate whether optical stimulation of the primary motor cortex can modulate chronic neuropathic pain in rats with infraorbital nerve constriction injury. Methods Animals were randomly divided into a trigeminal neuralgia group, a sham group, and a control group. Trigeminal neuropathic pain was generated via constriction of the infraorbital nerve and animals were treated via selective inhibition of calcitonin gene-related peptide in the trigeminal ganglion. We assessed alterations in behavioral responses in the pre-stimulation, stimulation, and post-stimulation conditions. In vivo extracellular recordings were obtained from the ventral posteromedial nucleus of the thalamus, and viral and α-CGRP expression were investigated in the primary motor cortex and trigeminal ganglion, respectively. Results We found that optogenetic stimulation significantly improved pain behaviors in the trigeminal neuralgia animals and it provided more significant improvement with inhibited α-CGRP state than active α-CGRP state. Electrophysiological recordings revealed decreases in abnormal thalamic firing during the stimulation-on condition. Conclusion Our findings suggest that optical motor cortex stimulation can alleviate pain behaviors in a rat model of trigeminal neuropathic pain. Transmission of trigeminal pain signals can be modulated via knock-down of α-CGRP and optical motor cortex stimulation.

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Large-scale all-optical dissection of motor cortex connectivity reveals a segregated functional organization of mouse forelimb representations

10.1101/2021.07.15.452461 ◽

2021 ◽

Author(s):

Francesco Resta ◽

Elena Montagni ◽

Giuseppe de Vito ◽

Alessandro Scaglione ◽

Anna Letizia Allegra Mascaro ◽

...

Keyword(s):

Motor Cortex ◽

Large Scale ◽

Functional Organization ◽

Voluntary Movements ◽

Motor Representation ◽

Activation Patterns ◽

Optogenetic Stimulation ◽

All Optical ◽

The Brain ◽

Stimulation Of

In rodent motor cortex, the rostral forelimb area (RFA) and the caudal forelimb area (CFA) are major actors in orchestrating the control of forelimb complex movements. However, their intrinsic connections and reciprocal functional organization are still unclear, limiting our understanding of how the brain coordinates and executes voluntary movements. Here we causally probed cortical connectivity and activation patterns triggered by transcranial optogenetic stimulation of ethologically relevant complex movements exploiting a novel large-scale all-optical method in awake mice. Results show specific activation features for each movement class, providing evidence for a segregated functional organization of CFA and RFA. Importantly, we identified a second discrete lateral grasping representation area, namely lateral forelimb area (LFA), with unique connectivity and activation patterns. Therefore, we propose the LFA as a distinct motor representation in the forelimb somatotopic motor map.

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Forelimb movements evoked by optogenetic stimulation of the macaque motor cortex

Nature Communications ◽

10.1038/s41467-020-16883-5 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 3

Author(s):

Hidenori Watanabe ◽

Hiromi Sano ◽

Satomi Chiken ◽

Kenta Kobayashi ◽

Yuko Fukata ◽

...

Keyword(s):

Motor Cortex ◽

Optogenetic Stimulation ◽

Forelimb Movements ◽

Stimulation Of

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Optogenetic Stimulation of The Motor Cortex Alleviates Neuropathic Pain in Rats of Infraorbital Nerve Injury With/Without CGRP Knock-Down

10.21203/rs.3.rs-48555/v1 ◽

2020 ◽

Author(s):

Jaisan Islam ◽

Elina KC ◽

Byeong Ho Oh ◽

Soochong Kim ◽

Sang-hwan Hyun ◽

...

Keyword(s):

Neuropathic Pain ◽

Motor Cortex ◽

Trigeminal Neuralgia ◽

Trigeminal Ganglion ◽

Primary Motor Cortex ◽

Infraorbital Nerve ◽

Motor Cortex Stimulation ◽

Trigeminal Neuropathic Pain ◽

Optogenetic Stimulation ◽

Stimulation Of

Abstract Background: Previous studies have reported that electrical stimulation of the motor cortex is effective in reducing trigeminal neuropathic pain; however, the effects of optical motor cortex stimulation remain unclear. Objective: The present study aimed to investigate whether optical stimulation of the primary motor cortex can modulate chronic neuropathic pain in rats with infraorbital nerve constriction injury.Methods: Animals were randomly divided into a trigeminal neuralgia group, a sham group, and a control group. Trigeminal neuropathic pain was generated via constriction of the infraorbital nerve and animals were treated via selective inhibition of calcitonin gene-related peptide in the trigeminal ganglion. We assessed alterations in behavioral responses in the pre-stimulation, stimulation, and post-stimulation conditions. In vivo extracellular recordings were obtained from the ventral posteromedial nucleus of the thalamus, and viral and α-CGRP expression were investigated in the primary motor cortex and trigeminal ganglion, respectively.Results: We found that optogenetic stimulation significantly improved pain behaviors in the trigeminal neuralgia animals and it provided more significant improvement with inhibited α-CGRP state than active α-CGRP state. Electrophysiological recordings revealed decreases in abnormal thalamic firing during the stimulation-on condition.Conclusion: Our findings suggest that optical motor cortex stimulation can alleviate pain behaviors in a rat model of trigeminal neuropathic pain. Transmission of trigeminal pain signals can be modulated via knock-down of α-CGRP and optical motor cortex stimulation.

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