Peripheral optogenetic stimulation induces whisker movement and sensory perception in head-fixed mice

Park, Sunmee; Bandi, Akhil; Lee, Christian R.; Margolis, David J.

doi:10.7554/elife.14140

Cited by 21 publications

(30 citation statements)

References 62 publications

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“…) and physiological (Park et al . ; Abe & Yawo, ; Arcourt et al . ) perspectives, a number of technical difficulties have precluded the application (Montgomery et al .…”

Section: Introductionmentioning

confidence: 99%

“…To date, most optogenetic applications have focused on the central nervous system (CNS) (Galvan et al 2017;Rost et al 2017) and it has rarely been applied to the peripheral nervous system (PNS). Although the application of optogenetics to the PNS has clear advantages for both therapeutic (Llewellyn et al 2010;Daou et al 2013;Liske et al 2013;Copits et al 2016;Iyer et al 2016;Srinivasan et al 2018) and physiological (Park et al 2016;Abe & Yawo, 2017;Arcourt et al 2017) perspectives, a number of technical difficulties have precluded the application (Montgomery et al 2016).…”

Section: Introductionmentioning

confidence: 99%

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Optogenetic recruitment of spinal reflex pathways from large‐diameter primary afferents in non‐transgenic rats transduced with AAV9/Channelrhodopsin 2

Kubota

Wupuer

Kudo

et al. 2019

The Journal of Physiology

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Key points We demonstrated optical activation of primary somatosensory afferents with high selectivity to fast‐conducting fibres by means of adeno‐associated virus 9 (AAV9)‐mediated gene transduction in dorsal root ganglion (DRG) neurons. AVV9 expressing green fluorescent protein showed high selectivity and transduction efficiency for fast‐conducting, large‐sized DRG neurons. Compared with conventional electrical stimulation, optically elicited volleys in primary afferents had higher sensitivity with stimulus amplitude, but lower sensitivity with stimulus frequency. Optically elicited dorsal root volleys activated postsynaptic neurons in the segmental spinal pathway. This proposed technique will help establish the causal relationships between somatosensory afferent inputs and neural responses in the CNS as well as behavioural outcomes in higher mammals where transgenic animals are not available. Abstract Previously, fundamental structures and their mode of action in the spinal reflex circuit were determined by confirming their input–output relationship using electrophysiological techniques. In those experiments, the electrical stimulation of afferent fibres was used as a core element to identify different types of reflex pathways; however, a major disadvantage of this technique is its non‐selectivity. In this study, we investigated the selective activation of large‐diameter afferents by optogenetics combined with a virus vector transduction technique (injection via the sciatic nerve) in non‐transgenic male Jcl:Wistar rats. We found that green fluorescent protein gene transduction of rat dorsal root ganglion (DRG) neurons with a preference for medium‐to‐large‐sized cells was achieved using the adeno‐associated virus 9 (AAV9) vector compared with the AAV6 vector (P = 0.021). Furthermore, the optical stimulation of Channelrhodopsin 2 (ChR2)‐expressing DRG neurons (transduced by AAV9) produced compound action potentials in afferent nerves originating from fast‐conducting nerve fibres. We also confirmed that physiological responses to different stimulus amplitudes were comparable between optogenetic and electrophysiological activation. However, compared with electrically elicited responses, the optically elicited responses had lower sensitivity with stimulus frequency. Finally, we showed that afferent volleys evoked by optical stimulation were sufficient to activate postsynaptic neurons in the spinal reflex arc. These results provide new ways for understanding the role of sensory afferent input to the central nervous system regarding behavioural control, especially when genetically manipulated animals are not available, such as higher mammals including non‐human primates.

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“…) and physiological (Park et al . ; Abe & Yawo, ; Arcourt et al . ) perspectives, a number of technical difficulties have precluded the application (Montgomery et al .…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Optogenetic recruitment of spinal reflex pathways from large‐diameter primary afferents in non‐transgenic rats transduced with AAV9/Channelrhodopsin 2

Kubota

Wupuer

Kudo

et al. 2019

The Journal of Physiology

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“…Head-fixed mice can be trained to perform various whisker-based behavioral tasks, enabling the study of learning-related neural activity that would be otherwise difficult to interrogate (O’Connor et al, 2009; Huber et al, 2012; Margolis et al, 2014; Chen et al, 2015; Peron et al, 2015; Park et al, 2016). In the Go/NoGo tactile decision-making task of Chen et al (2013a,b), mice learn to discriminate between two or more textures presented to the whisker by licking (Go) for water reward in response to one of the textures, and withholding licking (NoGo) in response to the distractor textures.…”

Section: Introductionmentioning

confidence: 99%

Pupil Dynamics Reflect Behavioral Choice and Learning in a Go/NoGo Tactile Decision-Making Task in Mice

Lee

Margolis

2016

Front. Behav. Neurosci.

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The eye’s pupil undergoes dynamic changes in diameter associated with cognitive effort, motor activity and emotional state, and can be used to index brain state across mammalian species. Recent studies in head-fixed mice have linked arousal-related pupil dynamics with global neural activity as well as the activity of specific neuronal populations. However, it has remained unclear how pupil dynamics in mice report trial-by-trial performance of behavioral tasks, and change on a longer time scale with learning. We measured pupil dynamics longitudinally as mice learned to perform a Go/NoGo tactile decision-making task. Mice learned to discriminate between two textures presented to the whiskers by licking in response to the Go texture (Hit trial) or withholding licking in response to the NoGo texture (Correct Reject trial, CR). Characteristic pupil dynamics were associated with behavioral choices: large-amplitude pupil dilation prior to and during licking accompanied Hit and False Alarm (FA) responses, while smaller amplitude dilation followed by constriction accompanied CR responses. With learning, the choice-dependent pupil dynamics became more pronounced, including larger amplitude dilations in both Hit and FA trials and earlier onset dilations in Hit and CR trials. A more pronounced constriction was also present in CR trials. Furthermore, pupil dynamics predicted behavioral choice increasingly with learning to greater than 80% accuracy. Our results indicate that pupil dynamics reflect behavioral choice and learning in head-fixed mice, and have implications for understanding decision- and learning-related neuronal activity in pupil-linked neural circuits.

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“…Light stimuli and recording methods followed our previous work (Park et al 2016). Briefly, a blue 117 460 nm high-power LED (Prizmatix) was coupled to a 200 µm diameter optical fiber (Thorlabs), 118 producing a 2-3 mm spot of light on the face.…”

Section: Stimuli and Video Recording 116mentioning

confidence: 99%

“…Non-invasive, direct stimulation of paralyzed muscle 51 that produces naturalistic movements is highly desirable but has not been achieved using 52 traditional methods. 53 54 Our previous work established a method for non-invasive control of whisker movements in mice 55 using transdermal photostimulation of the optogenetic actuator channelrhodopsin-2 (ChR2) 56 expressed in whisker pad muscles (Park et al 2016). Spot illumination of the rostral whisker pad 57 with blue light in Emx1-ChR2 mice, as used in the previous and current work, evokes whisker 58 protractions by activating extrinsic protractor muscles pars media superior and pars media 59 inferior of M. nasolabialis profundus and also intrinsic follicular muscles (Haidarliu et al 2015, 60 muscles are composed of distinctive fiber type (Haidarliu et al 2010, Jin et al 2004.…”

Section: Introduction 38mentioning

confidence: 99%

Optogenetic and transcriptomic interrogation of enhanced muscle function in the paralyzed mouse whisker pad

Vajtay

Bandi

Upadhyay

et al. 2018

Preprint

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14The functional state of denervated muscle is a critical factor in the ability to restore movement 15 after injury-or disease-related paralysis. Here we used peripheral optogenetic stimulation and 16 transcriptome profiling in the mouse whisker system to investigate the time course of changes in 17 neuromuscular function following complete unilateral facial nerve transection. While most 18 skeletal muscles rapidly lose functionality after lower motor neuron denervation, optogenetic 19 muscle stimulation of the paralyzed whisker pad revealed sustained increases in the sensitivity, 20 velocity, and amplitude of whisker movements, and reduced fatigability, starting 48 h after 21 denervation. RNA-seq analysis showed distinct regulation of multiple gene families in 22 denervated whisker pad muscles compared to the atrophy-prone soleus, including prominent 23 changes in ion channels and contractile fibers. Together, our results define the unique functional 24 and transcriptomic landscape of denervated facial muscles, and have general implications for 25 restoring movement after neuromuscular injury or disease. 26 27New & Noteworthy: Optogenetic activation of muscle can be used to non-invasively induce 31 movements and probe muscle function. We used this technique in mice to investigate changes 32 in whisker movements following facial nerve transection. We found unexpectedly enhanced 33 functional properties of whisker pad muscle following denervation, accompanied by unique 34 transcriptomic changes. Our findings highlight the utility of the mouse whisker pad for 35 investigating the restoration of movement after paralysis. 36 37 Haidarliu et al 2010, Park et al 2016), collectively referred to here as "whisker pad muscles". In 61 the present study, we used ChAT-ChR2 and Emx1-ChR2 mice to evoke whisker movements via 62 stimulation of the facial motor nerve (cranial nerve VII) or the whisker pad muscles, respectively. 63 This allowed us to investigate the functional changes that occur in nerve and muscle after the 64 paralysis of whisker movements caused by facial nerve transection. 65 66 One recent study used optogenetic muscle stimulation in the hindlimb triceps surae after sciatic 67 nerve lesion to demonstrate dramatic atrophy and loss of function (Magown et al 2015), 68consistent with classic studies in this system (Nelson 1969), that could be attenuated by daily 69 optogenetic activation. We considered it possible that whisker pad muscles undergo distinct 70 denervation-induced changes compared to other muscle types, in part because whisker pad 71 position of the nerve in ChAT-ChR2 mice, the buccal branch of the facial nerve (cranial nerve 126 VII) was targeted with the light spot at a position between the stylomastoid foramen, ventral to 127 the ear canal and caudal to the whisker pad. Different illumination positions in this region were 128 tested for each subject to optimize the evoked whisker protraction. To test effects on 129 fasciculations, dantrolene (1 mM) was applied subcutaneously to the lesioned (right-...

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Peripheral optogenetic stimulation induces whisker movement and sensory perception in head-fixed mice

Cited by 21 publications

References 62 publications

Optogenetic recruitment of spinal reflex pathways from large‐diameter primary afferents in non‐transgenic rats transduced with AAV9/Channelrhodopsin 2

Optogenetic recruitment of spinal reflex pathways from large‐diameter primary afferents in non‐transgenic rats transduced with AAV9/Channelrhodopsin 2

Pupil Dynamics Reflect Behavioral Choice and Learning in a Go/NoGo Tactile Decision-Making Task in Mice

Optogenetic and transcriptomic interrogation of enhanced muscle function in the paralyzed mouse whisker pad

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