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

2019 ◽  
Author(s):  
Yi Chen ◽  
Filip Sobczak ◽  
Patricia Pais-Roldán ◽  
Cornelius Schwarz ◽  
Alan P. Koretsky ◽  
...  

ABSTRACTThe optogenetically driven manipulation of circuit-specific activity enabled functional causality studies in animals, but its global effect on the brain is rarely reported. Here, we applied simultaneous fMRI with calcium recording to map brain-wide activity by optogenetic activation of fibers running in one orientation along the corpus callosum(CC) connecting the barrel cortex(BC). Robust positive BOLD signals were detected in the ipsilateral BC due to antidromic activity, which spread to ipsilateral motor cortex(MC) and posterior thalamus(PO). In the orthodromic target (contralateral barrel cortex), positive BOLD signals were reliably evoked by 2Hz light pulses, whereas 40Hz light pulses led to a reversed sign of BOLD - indicative of CC-mediated inhibition. This presumed optogenetic CC-mediated inhibition was further elucidated by pairing light with peripheral whisker stimulation at varied inter-stimulus intervals. Whisker induced positive BOLD, and calcium signals were reduced at inter-stimulus intervals of 50/100ms. The calcium-amplitude modulation (AM)-based correlation with whole-brain fMRI signal revealed that the inhibitory effects spread to contralateral BC as well as ipsilateral MC and PO. This work raises the need of fMRI to elucidate the brain-wide network activation in response to projection-specific optogenetic stimulation.

2020 ◽  
Vol 30 (11) ◽  
pp. 5885-5898
Author(s):  
Yi Chen ◽  
Filip Sobczak ◽  
Patricia Pais-Roldán ◽  
Cornelius Schwarz ◽  
Alan P Koretsky ◽  
...  

Abstract Optogenetically driven manipulation of circuit-specific activity enables causality studies, but its global brain-wide effect is rarely reported. Here, we applied simultaneous functional magnetic resonance imaging (fMRI) and calcium recording with optogenetic activation of the corpus callosum (CC) connecting barrel cortices (BC). Robust positive BOLD was detected in the ipsilateral BC due to antidromic activity, spreading to the ipsilateral motor cortex (MC), and posterior thalamus (PO). In the orthodromic target, positive BOLD was reliably evoked by 2 Hz light pulses, whereas 40 Hz light pulses led to reduced calcium, indicative of CC-mediated inhibition. This presumed optogenetic CC-mediated inhibition was further elucidated by pairing light pulses with whisker stimulation at varied interstimulus intervals. Whisker-induced positive BOLD and calcium signals were reduced at intervals of 50/100 ms. The calcium-amplitude-modulation-based correlation with whole-brain fMRI signal revealed that the inhibitory effects spread to contralateral BC, ipsilateral MC, and PO. This work raises the need for fMRI to elucidate the brain-wide network activation in response to optogenetic stimulation.


2012 ◽  
Vol 112 (7) ◽  
pp. 1215-1222 ◽  
Author(s):  
Takashi Suzuki ◽  
Yasuhiro Ooi ◽  
Junji Seki

The present study aims to validate the applicability of infrared (IR) thermal imaging for the study of brain function through experiments on the rat barrel cortex. Regional changes in neural activity within the brain produce alterations in local thermal equilibrium via increases in metabolic activity and blood flow. We studied the relationship between temperature change and neural activity in anesthetized rats using IR imaging to visualize stimulus-induced changes in the somatosensory cortex of the brain. Sensory stimulation of the vibrissae (whiskers) was given for 10 s using an oscillating whisker vibrator (5-mm deflection at 10, 5, and 1 Hz). The brain temperature in the observational region continued to increase significantly with whisker stimulation. The mean peak recorded temperature changes were 0.048 ± 0.028, 0.054 ± 0.036, and 0.097 ± 0.015°C at 10, 5, and 1 Hz, respectively. We also observed that the temperature increase occurred in a focal spot, radiating to encompass a larger region within the contralateral barrel cortex region during single-whisker stimulation. Whisker stimulation also produced ipsilateral cortex temperature increases, which were localized in the same region as the pial arterioles. Temperature increase in the barrel cortex was also observed in rats treated with a calcium channel blocker (nimodipine), which acts to suppress the hemodynamic response to neural activity. Thus the location and area of temperature increase were found to change in accordance with the region of neural activation. These results indicate that IR thermal imaging is viable as a functional quantitative neuroimaging technique.


2021 ◽  
Vol 15 ◽  
Author(s):  
Benedetta Mariani ◽  
Giorgio Nicoletti ◽  
Marta Bisio ◽  
Marta Maschietto ◽  
Roberto Oboe ◽  
...  

Since its first experimental signatures, the so called “critical brain hypothesis” has been extensively studied. Yet, its actual foundations remain elusive. According to a widely accepted teleological reasoning, the brain would be poised to a critical state to optimize the mapping of the noisy and ever changing real-world inputs, thus suggesting that primary sensory cortical areas should be critical. We investigated whether a single barrel column of the somatosensory cortex of the anesthetized rat displays a critical behavior. Neuronal avalanches were recorded across all cortical layers in terms of both multi-unit activities and population local field potentials, and their behavior during spontaneous activity compared to the one evoked by a controlled single whisker deflection. By applying a maximum likelihood statistical method based on timeseries undersampling to fit the avalanches distributions, we show that neuronal avalanches are power law distributed for both multi-unit activities and local field potentials during spontaneous activity, with exponents that are spread along a scaling line. Instead, after the tactile stimulus, activity switches to a transient across-layers synchronization mode that appears to dominate the cortical representation of the single sensory input.


2017 ◽  
Author(s):  
David A. McVea ◽  
Timothy H. Murphy ◽  
Majid H. Mohajerani

AbstractA prominent feature of the cortical systems controlling the whiskers in the adult rodent is tight coupling between sensory and motor systems. Stimulation of the whiskers evokes activation of discrete motor regions of cortex shortly after activation of the sensory cortex. To explore the factors that direct the development of sensorimotor functional connectivity, we recorded spontaneous and whisker-evoked cortical activity using voltage-sensitive imaging over a large (7X7 mm) craniotomy in postnatal rats (day 5-12) under anesthesia. We found that spontaneous bursts of activity in the barrel cortex were correlated predominantly with activity in motor (anterio-medial) cortex, at ages before whisker stimulation evoked activation in this area. Intracortical microstimulation and anatomical tracing experiments confirmed there were no functional or anatomical intracortical sensorimotor connections. We interpret these results as evidence that the spontaneous patterns of activity in the cortex synchronize functionally related regions of the brain prior to their maturation.Author ContributionsD.A.M, T.H.M., and M.H.M. designed the study. D.A.M, and M.H.M performed the experiments and analyzed the data and wrote the manuscript, which all authors commented on and edited. T.H.M. and M.H.M. supervised the study.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Changpeng Wang ◽  
Siwei Zhang ◽  
Yuefei Zou ◽  
Hongzhao Ma ◽  
Donglang Jiang ◽  
...  

Abstract Background Some neuropsychological diseases are associated with abnormal thiamine metabolism, including Korsakoff–Wernicke syndrome and Alzheimer’s disease. However, in vivo detection of the status of brain thiamine metabolism is still unavailable and needs to be developed. Methods A novel PET tracer of 18F-deoxy-thiamine was synthesized using an automated module via a two-step route. The main quality control parameters, such as specific activity and radiochemical purity, were evaluated by high-performance liquid chromatography (HPLC). Radiochemical concentration was determined by radioactivity calibrator. Metabolic kinetics and the level of 18F-deoxy-thiamine in brains of mice and marmosets were studied by micro-positron emission tomography/computed tomography (PET/CT). In vivo stability, renal excretion rate, and biodistribution of 18F-deoxy-thiamine in the mice were assayed using HPLC and γ-counter, respectively. Also, the correlation between the retention of cerebral 18F-deoxy-thiamine in 60 min after injection as represented by the area under the curve (AUC) and blood thiamine levels was investigated. Results The 18F-deoxy-thiamine was stable both in vitro and in vivo. The uptake and clearance of 18F-deoxy-thiamine were quick in the mice. It reached the max standard uptake value (SUVmax) of 4.61 ± 0.53 in the liver within 1 min, 18.67 ± 7.04 in the kidney within half a minute. The SUV dropped to 0.72 ± 0.05 and 0.77 ± 0.35 after 60 min of injection in the liver and kidney, respectively. After injection, kidney, liver, and pancreas exhibited high accumulation level of 18F-deoxy-thiamine, while brain, muscle, fat, and gonad showed low accumulation concentration, consistent with previous reports on thiamine distribution in mice. Within 90 min after injection, the level of 18F-deoxy-thiamine in the brain of C57BL/6 mice with thiamine deficiency (TD) was 1.9 times higher than that in control mice, and was 3.1 times higher in ICR mice with TD than that in control mice. The AUC of the tracer in the brain of marmosets within 60 min was 29.33 ± 5.15 and negatively correlated with blood thiamine diphosphate levels (r = − 0.985, p = 0.015). Conclusion The 18F-deoxy-thiamine meets the requirements for ideal PET tracer for in vivo detecting the status of cerebral thiamine metabolism.


1955 ◽  
Vol 33 (3) ◽  
pp. 395-403 ◽  
Author(s):  
Irving H. Heller ◽  
K. A. C. Elliott

Per unit weight, cerebral and cerebellar cortex respire much more actively than corpus callosum. The rate per cell nucleus is highest in cerebral cortex, lower in corpus callosum, and still lower in cerebellar cortex. The oxygen uptake rates of the brain tumors studied, with the exception of an oligodendroglioma, were about the same as that of white matter on the weight basis but lower than that of cerebral cortex or white matter on the cell basis. In agreement with previous work, an oligodendroglioma respired much more actively than the other tumors. The rates of glycolysis of the brain tumors per unit weight were low but, relative to their respiration rate, glycolysis was higher than in normal gray or white matter. Consideration of the figures obtained leads to the following tentative conclusions: Glial cells of corpus callosum respire more actively than the neurons of the cerebellar cortex. Neurons of the cerebral cortex respire on the average much more actively than neurons of the cerebellar cortex or glial cells. Considerably more than 70% of the oxygen uptake by cerebral cortex is due to neurons. The oxygen uptake rates of normal oligodendroglia and astrocytes are probably about the same as the rates found per nucleus in an oligodendroglioma and in astrocytomas; oligodendroglia respire much more actively than astrocytes.


2015 ◽  
Vol 26 (3) ◽  
pp. 495-505 ◽  
Author(s):  
Meredith O. Sweeney ◽  
Agnieszka Collins ◽  
Shae B. Padrick ◽  
Bruce L. Goode

Branched actin filament networks in cells are assembled through the combined activities of Arp2/3 complex and different WASP/WAVE proteins. Here we used TIRF and electron microscopy to directly compare for the first time the assembly kinetics and architectures of actin filament networks produced by Arp2/3 complex and dimerized VCA regions of WAVE1, WAVE2, or N-WASP. WAVE1 produced strikingly different networks from WAVE2 or N-WASP, which comprised unexpectedly short filaments. Further analysis showed that the WAVE1-specific activity stemmed from an inhibitory effect on filament elongation both in the presence and absence of Arp2/3 complex, which was observed even at low stoichiometries of WAVE1 to actin monomers, precluding an effect from monomer sequestration. Using a series of VCA chimeras, we mapped the elongation inhibitory effects of WAVE1 to its WH2 (“V”) domain. Further, mutating a single conserved lysine residue potently disrupted WAVE1's inhibitory effects. Taken together, our results show that WAVE1 has unique activities independent of Arp2/3 complex that can govern both the growth rates and architectures of actin filament networks. Such activities may underlie previously observed differences between the cellular functions of WAVE1 and WAVE2.


1966 ◽  
Vol 101 (3) ◽  
pp. 591-597 ◽  
Author(s):  
R M O'Neal ◽  
R E Koeppe ◽  
E I Williams

1. Free glutamic acid, aspartic acid, glutamic acid from glutamine and, in some instances, the glutamic acid from glutathione and the aspartic acid from N-acetyl-aspartic acid were isolated from the brains of sheep and assayed for radioactivity after intravenous injection of [2-(14)C]glucose, [1-(14)C]acetate, [1-(14)C]butyrate or [2-(14)C]propionate. These brain components were also isolated and analysed from rats that had been given [2-(14)C]propionate. The results indicate that, as in rat brain, glucose is by far the best precursor of the free amino acids of sheep brain. 2. Degradation of the glutamate of brain yielded labelling patterns consistent with the proposal that the major route of pyruvate metabolism in brain is via acetyl-CoA, and that the short-chain fatty acids enter the brain without prior metabolism by other tissue and are metabolized in brain via the tricarboxylic acid cycle. 3. When labelled glucose was used as a precursor, glutamate always had a higher specific activity than glutamine; when labelled fatty acids were used, the reverse was true. These findings add support and complexity to the concept of the metabolic; compartmentation' of the free amino acids of brain. 4. The results from experiments with labelled propionate strongly suggest that brain metabolizes propionate via succinate and that this metabolic route may be a limited but important source of dicarboxylic acids in the brain.


2021 ◽  
Author(s):  
Anthony Renard ◽  
Evan Harrell ◽  
Brice Bathallier

Abstract Rodents depend on olfaction and touch to meet many of their fundamental needs. The joint significance of these sensory systems is underscored by an intricate coupling between sniffing and whisking. However, the impact of simultaneous olfactory and tactile inputs on sensory representations in the cortex remains elusive. To study these interactions, we recorded large populations of barrel cortex neurons using 2-photon calcium imaging in head-fixed mice during olfactory and tactile stimulation. We find that odors alter barrel cortex activity in at least two ways, first by enhancing whisking, and second by central cross-talk that persists after whisking is abolished by facial nerve sectioning. Odors can either enhance or suppress barrel cortex neuronal responses, and while odor identity can be decoded from population activity, it does not interfere with the tactile representation. Thus, barrel cortex represents olfactory information which, in the absence of learned associations, is coded independently of tactile information.


2017 ◽  
Vol 8 (1) ◽  
pp. e00877 ◽  
Author(s):  
Fabio Richlan ◽  
Juliane Schubert ◽  
Rebecca Mayer ◽  
Florian Hutzler ◽  
Martin Kronbichler

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