MRI-guided robotic arm drives optogenetic fMRI with concurrent Ca2+ recording

Chen, Yi; Pais-Roldán, Patricia; Chen, Xuming; Frosz, Michael H.; Yu, Xin

doi:10.1038/s41467-019-10450-3

Cited by 25 publications

(22 citation statements)

References 70 publications

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“…For example, mapping the organization and connectivity of columns in primates requires precise stimulation of single columns, roughly 200 μm in sizes. Compared to the electrical stimulation, TFOE offers a spatial precision finer than 200 μm and MRI compatibility, making it possible to assess functional outcome of the stimulation through MRI-guided insertion 58 and brain fMRI recording in humans and non-human primates. It is also non-genetic, which overcoming the challenges facing by optogenetics in primates.…”

Section: Discussionmentioning

confidence: 99%

Non-genetic photoacoustic stimulation of single neurons by a tapered fiber optoacoustic emitter

et al. 2021

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Neuromodulation at high spatial resolution poses great significance in advancing fundamental knowledge in the field of neuroscience and offering novel clinical treatments. Here, we developed a tapered fiber optoacoustic emitter (TFOE) generating an ultrasound field with a high spatial precision of 39.6 µm, enabling optoacoustic activation of single neurons or subcellular structures, such as axons and dendrites. Temporally, a single acoustic pulse of sub-microsecond converted by the TFOE from a single laser pulse of 3 ns is shown as the shortest acoustic stimuli so far for successful neuron activation. The precise ultrasound generated by the TFOE enabled the integration of the optoacoustic stimulation with highly stable patch-clamp recording on single neurons. Direct measurements of the electrical response of single neurons to acoustic stimulation, which is difficult for conventional ultrasound stimulation, have been demonstrated. By coupling TFOE with ex vivo brain slice electrophysiology, we unveil cell-type-specific responses of excitatory and inhibitory neurons to acoustic stimulation. These results demonstrate that TFOE is a non-genetic single-cell and sub-cellular modulation technology, which could shed new insights into the mechanism of ultrasound neurostimulation.

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Section: Discussionmentioning

confidence: 99%

Non-genetic photoacoustic stimulation of single neurons by a tapered fiber optoacoustic emitter

et al. 2021

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“…1a) [56, 61]. Based on our previous work [62], an MRI-guided robotic arm was used to provide high flexibility to insert the optical fiber and sufficient targeting accuracy on the ∼200 µm callosal fiber bundle for multi-modal fMRI. The most salient BOLD fMRI signal evoked by CC optogenetic stimulation was detected at the ipsilateral BC housing the labeled CPN (n = 8 animals, Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Before transferring the animal to the MRI scanner, two craniotomies were performed: one for fixed fiber implantation to record calcium signals from BC, and the other one for dynamic insertion of the optical fiber to stimulate the CC using optogenetics (dynamic insertion was achieved by using a remote positioning tool [62]). The animal was placed on a stereotaxic frame, the scalp was opened and two ∼1.5 mm diameter burr holes were drilled on the skull.…”

Section: Methodsmentioning

confidence: 99%

Mapping the brain-wide network effects by optogenetic activation of the corpus callosum

Chen

Sobczak

Pais-Roldán

et al. 2019

Preprint

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words) 36The optogenetically driven manipulation of circuit-specific activity enabled functional causality studies in animals, 37 but its global effect on the brain is rarely reported. Here, we applied simultaneous fMRI with calcium recording to 38 map brain-wide activity by optogenetic activation of fibers running in one orientation along the corpus callosum(CC) 39 connecting the barrel cortex(BC). Robust positive BOLD signals were detected in the ipsilateral BC due to 40 antidromic activity, which spread to ipsilateral motor cortex(MC) and posterior thalamus(PO). In the orthodromic 41 target (contralateral barrel cortex), positive BOLD signals were reliably evoked by 2Hz light pulses, whereas 40Hz 42 light pulses led to a reversed sign of BOLD -indicative of CC-mediated inhibition. This presumed optogenetic CC-43 mediated inhibition was further elucidated by pairing light with peripheral whisker stimulation at varied inter-44 stimulus intervals. Whisker induced positive BOLD, and calcium signals were reduced at inter-stimulus intervals 45 of 50/100ms. The calcium-amplitude modulation (AM)-based correlation with whole-brain fMRI signal revealed 46 that the inhibitory effects spread to contralateral BC as well as ipsilateral MC and PO. This work raises the need of 47 ensure the activation of neuronal ensembles of interest [1][2][3][4]. Optogenetic tools have revolutionized the strategy to 51 perturb or manipulate the behavior of animals [5][6][7][8]. To interpret the linkage of the brain function to specific 52 behavioral readout relies on the assumed circuit-specific manipulation through in vivo optogenetic activation [9-53 12]. Optogenetic activation of numerous brain sites and defined neuronal populations in animals has been very 54 successful to modulate behavior. However, there is a lack of systematic mapping of the result of specific modulation 55 on brain-wide network activity, which may relay and affect the proposed link between function and behavior. 56Progress in this direction depends on the combined application of methods to explore large scale brain dynamics as 57 well [13][14][15][16]. One useful method for this purpose is functional magnetic resonance imaging (fMRI) , which has 58 been successfully combined with optogenetics [17][18][19][20][21][22]. We use here a method that adds GCaMP-mediated calcium 59 recordings through an optical fiber for concurrent fMRI and neuronal calcium signal recording [23][24][25][26][27]. This multi-60 modal cross-scale brain dynamic mapping scheme allows elucidating network activity upon circuit-specific 61 optogenetic activation on the specific target level as well as across large brain regions [19,[23][24][25][27][28][29]. 62Corpus callosum (CC), the major neural fiber bundles connecting the two hemispheres, plays a critical role to 63 mediate the interhemispheric cortico-cortical connections [30][31][32]. Despite the highly-correlated structural 64 anomalies of the CC with a wide range of disorders, e.g., schizophrenia [33, 34], autism [35, 36], epilepsy [37, 3...

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“…Recent advances indicate that abnormal myelination can occur in schizophrenia patients, such that using brain imaging can detect abnormalities of the white matter (WM), and that electroand magnetoencephalography (EEG/MEG) and functional magnetic resonance imaging (fMRI) show neuronal dysconnectivity (4). These changes in myelination, excitability, and functional connectivity can be caused by genetic and epigenetic transcriptional dysregulation, triggering and largely relying upon persistent Ca 2+ signaling modulation (5)(6)(7). To date, there are challenges for animal models of the development of severe mental illnesses.…”

Section: Introductionmentioning

confidence: 99%

Modulation of Stem Cells as Therapeutics for Severe Mental Disorders and Cognitive Impairments

et al. 2020

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Intranasal-to-brain delivery of drugs and stem cells or local delivery with the guidance of brain imaging techniques may provide a unique new approach for treating psychiatric disorders. It is also expected that preconditioning stem cell therapy following precise brain imaging as pathological confirmation has high potential if translated to cell clinic use. Generally, modulable cell transplantation followed by stimulations should provide paracrine protection, synaptic modulation, and myelin repair for the brain in SMI.

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MRI-guided robotic arm drives optogenetic fMRI with concurrent Ca2+ recording

Cited by 25 publications

References 70 publications

Non-genetic photoacoustic stimulation of single neurons by a tapered fiber optoacoustic emitter

Non-genetic photoacoustic stimulation of single neurons by a tapered fiber optoacoustic emitter

Mapping the brain-wide network effects by optogenetic activation of the corpus callosum

Modulation of Stem Cells as Therapeutics for Severe Mental Disorders and Cognitive Impairments

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