Probing activation‐induced neurochemical changes using optogenetics combined with functional magnetic resonance spectroscopy: a feasibility study in the rat primary somatosensory cortex

Just, Nathalie; Faber, Cornelius

doi:10.1111/jnc.14799

Cited by 20 publications

(27 citation statements)

References 34 publications

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“…To further extend this proposition and bring more specificity to the technique, 1 H-fMRS coupled to optogenetics (o-fMRS) is being explored. 42,68,69 Optogenetics allows the stimulation of specific cell populations with strong laser light provided a virus construct including an opsin has been previously intracranially injected or that opsin-expressing transgenic animals are used. 93 The successful coupling of optogenetic methodologies to fMRI (o-fMRI) gradually revolutionized the field of neuroscience, enabling further understanding of brain circuit mechanisms and follow-up of causal activities across neuronal networks through gene expression along axonal projections.…”

Section: Applications Of Fmrs In Small Animalsmentioning

confidence: 99%

“…For longer paradigms (>10 minutes), one should investigate potential habituation/adaption effects and their impact on the metabolism, while the presence of brain activation may also vary spatially as a function of time. 30 Although not absolutely necessary, it is recommended to take into account the BOLD effects 1 : during acquisitions for positioning the VOI over the core of the BOLD activation, with a dynamic acquisition it may be possible to visualize the slight increase in the water (or NAA or tCr) peak height during stimulation, indicative of sensitivity to the stimulation 42 ; and 2 during data processing, checking that the VOI positioning over the BOLD-activated area leads to a detectable BOLD effect is also indicative of the sensitivity of the technique, and may help in terms of reproducibility and classification across a population. This procedure was used by Boillat et al 101 A comparison of functional neurochemical profiles by averaging metabolites across a population of rodents should be performed.…”

Section: Recommendations For Performing 1 H-fmrs In Rodentsmentioning

confidence: 99%

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Proton functional magnetic resonance spectroscopy in rodents

Just

2020

NMR in Biomedicine

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Proton functional magnetic resonance spectroscopy ( 1 H-fMRS) in the human brain is able to assess and quantify the metabolic response due to localized brain activity.Currently, 1 H-fMRS of the human brain is complementary to functional magnetic resonance imaging (fMRI) and a recommended technique at high field strengths (>7 T) for the investigation of neurometabolic couplings, thereby providing insight into the mechanisms underlying brain activity and brain connectivity. Understanding typical healthy brain metabolism during a task is expected to provide a baseline from which to detect and characterize neurochemical alterations associated with various neurological or psychiatric disorders and diseases. It is of paramount importance to resolve fundamental questions related to the regulation of neurometabolic processes. New techniques such as optogenetics may be coupled to fMRI and fMRS to bring more specificity to investigations of brain cell populations during cerebral activation thus enabling a higher link to molecular changes and therapeutic advances. These rather novel techniques are mainly available for rodent applications and trigger renewed interest in animal fMRS. However, rodent fMRS remains fairly confidential due to its inherent low signal-to-noise ratio and its dependence on anesthesia. For instance, the accurate determination of metabolic concentration changes during stimulation requires robust knowledge of the physiological environment of the measured region of interest linked to anesthesia in most cases. These factors may also have a strong influence on B0 homogeneity. Therefore, a degree of calibration of the stimulus strength and duration may be needed for increased knowledge of the underpinnings of cerebral activity. Here, we propose an early review of the current status of 1 H-fMRS in rodents and summarize current difficulties and future perspectives.

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Section: Applications Of Fmrs In Small Animalsmentioning

confidence: 99%

Section: Recommendations For Performing 1 H-fmrs In Rodentsmentioning

confidence: 99%

Proton functional magnetic resonance spectroscopy in rodents

Just

2020

NMR in Biomedicine

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“…Also, using awake MRS in mice, we may address physiological and/or pathological questions by combining with other modalities such as positron emission tomography 34, 35, 36 . Moreover, this method can be combined with optogenetics 37 and chemogenetics for further validating the mechanistic link between MRS findings and neural activities. Lastly, given that glial cells, such as astrocytes, are also known to contribute to Glu metabolism 38 , there are likely other factors, particularly in the pathological conditions, that contribute to MRS neurotransmitter measures besides neuronal activity, which should be addressed in future study.…”

Section: Resultsmentioning

confidence: 99%

MRS-measured Glutamate versus GABA reflects excitatory versus inhibitory neural activities in awake mice

Takado

Takuwa

Sampei

et al. 2020

Preprint

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There is growing interest in the use of magnetic resonance spectroscopy (MRS) to relate brain functions with the concentrations of glutamate (Glu; chief excitatory neurotransmitter) and gamma-aminobutyric acid (GABA; chief inhibitory neurotransmitter) in specific regions. However, it remains unclear how robustly MRS-measured Glu and GABA reflect activities of excitatory and inhibitory neurons, respectively. To address this issue, we conducted MRS measurements of Glu and GABA along with large field-of-view, two-photon mesoscopic imaging of calcium signals in excitatory and inhibitory neurons in the same brain region of living, unanesthetized mice. For monitoring stimulus-driven activations of a brain region, MRS signals and mesoscopic neural activities were measured during two consecutive sessions of 15-min prolonged sensory stimulations. In the first session, activities of putative excitatory neurons were increased, while activities of inhibitory neurons remained at the baseline level. In the second half, while activities of excitatory neurons remained elevated, activities of inhibitory neurons were significantly enhanced. Correspondingly, the concentration of Glu increased without changes in GABA levels in the first MRS session, and the GABA concentration markedly increased from the baseline in the second session. We also assessed regional neurochemical and functional statuses related to spontaneous neural firing by measuring MRS signals and neuronal activities in a mouse model of Dravet syndrome under a resting condition without any task and stimuli. Mesoscopic assessments showed that activities of inhibitory neurons in the cortex were diminished relative to wild-type mice in contrast to spared activities of excitatory neurons. Consistent with these observations, the Dravet model exhibited lower concentrations of GABA than wild-type controls. Collectively, the current investigations demonstrate that the MRS-measured Glu and GABA can reflect spontaneous and stimulated activities of neurons producing and releasing these neurotransmitters in an awake condition.

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“…Progress in this direction depends on the combined application of methods to explore large scale brain dynamics as well [13–16]. One useful method for this purpose is functional magnetic resonance imaging (fMRI), which has been successfully combined with optogenetics [17–22]. We use here a method that adds GCaMP-mediated calcium recordings through an optical fiber for concurrent fMRI and neuronal calcium signal recording [23–27].…”

Section: Introductionmentioning

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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Probing activation‐induced neurochemical changes using optogenetics combined with functional magnetic resonance spectroscopy: a feasibility study in the rat primary somatosensory cortex

Cited by 20 publications

References 34 publications

Proton functional magnetic resonance spectroscopy in rodents

Proton functional magnetic resonance spectroscopy in rodents

MRS-measured Glutamate versus GABA reflects excitatory versus inhibitory neural activities in awake mice

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

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