scholarly journals Multiplexed imaging of single-synapse activity and astroglial responses in the intact brain

2018 ◽  
Author(s):  
James P. Reynolds ◽  
Kaiyu Zheng ◽  
Dmitri A. Rusakov

All-optical registration of neuronal and astrocytic activities within the intact mammalian brain has improved significantly with recent advances in optical sensors and biophotonics. However, relating single-synapse release events and local astroglial responses to sensory stimuli in an intact animal has not hitherto been feasible. Here, we present a multiplexed multiphoton excitation imaging approach for assessing the relationship between presynaptic Ca2+ entry at thalamocortical axonal boutons and perisynaptic astrocytic Ca 2+ elevations, induced by whisker stimulation in the barrel cortex of C57BL/6 mice. We find that, unexpectedly, Ca 2+ elevations in the perisynaptic astrocytic regions consistently precede local presynaptic Ca 2+ signals during spontaneous brain activity associated with anaesthesia. The methods described here can be adapted to a variety of optical sensors and are compatible with experimental designs that might necessitate repeated sampling of single synapses over a longitudinal behavioural paradigm.

2019 ◽  
Author(s):  
Yair Deitcher ◽  
Yonatan Leibner ◽  
Sara Kutzkel ◽  
Neta Zylbermann ◽  
Michael London

AbstractThe axonal projections of the adrenergic system to the neocortex, originating from the locus coeruleus (LC), form a dense network. These axons release the neuromodulator norepinephrine (NE) which is involved in many cognitive functions such as attention, arousal, and working memory. Using two-photon Ca2+ imaging of NE axons in the cortex of awake mice, we investigated what drives their phasic activity. We discovered that NE axons in the primary somatosensory cortex responded robustly and reliably to somatosensory stimulation. Surprisingly, the same axons also responded to stimuli of other modalities (auditory and visual). Similar responses to all three modalities were observed in the primary visual cortex as well. These results indicate that phasic responses of NE axons to sensory stimuli provide a robust multimodal signal. However, despite the robustness, we also noticed consistent variations in the data. For example, responses to whisker stimulations were larger than to auditory and visual stimulations in both the barrel and the visual cortices. To test whether the variations in NE axonal responses can carry behaviorally meaningful information, we trained mice in an associative auditory fear conditioning paradigm. We found that following conditioning the response of NE axons increased only for CS+, namely the signal undergoes experience-dependent plasticity and is specific to meaningful sounds. To test if variations in NE axonal responses can differentially affect the cortical microcircuit, we used dual-color two-photon Ca2+ imaging and studied the relationship between the activity of NE axons and local dendrites. We found dendritic Ca2+ signals in barrel cortex in response to auditory stimuli, but these responses were variable and unreliable. Strikingly, the probability of such dendritic signals increased nonlinearly with the Ca2+ signals of NE axons. Our results demonstrate that the phasic activity of the noradrenergic neurons may serve as a robust multimodal and plastic signal in sensory cortices. Furthermore, the variations in the NE axonal activity carry behaviorally meaningful signals and can predict the probability of local dendritic Ca2+ events.


eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Zhiwei Ma ◽  
Nanyin Zhang

Spontaneous brain activity, typically investigated using resting-state fMRI (rsfMRI), provides a measure of inter-areal resting-state functional connectivity (RSFC). Although it has been established that RSFC is non-stationary, previous dynamic rsfMRI studies mainly focused on revealing the spatial characteristics of dynamic RSFC patterns, but the temporal relationship between these RSFC patterns remains elusive. Here we investigated the temporal organization of characteristic RSFC patterns in awake rats and humans. We found that transitions between RSFC patterns were not random but followed specific sequential orders. The organization of RSFC pattern transitions was further analyzed using graph theory, and pivotal RSFC patterns in transitions were identified. This study has demonstrated that spontaneous brain activity is not only nonrandom spatially, but also nonrandom temporally, and this feature is well conserved between rodents and humans. These results offer new insights into understanding the spatiotemporal dynamics of spontaneous activity in the mammalian brain.


2020 ◽  
Author(s):  
Yaoheng Yang ◽  
Christopher Pham Pacia ◽  
Dezhuang Ye ◽  
Lifei Zhu ◽  
Hongchae Baek ◽  
...  

AbstractSonogenetics, which uses ultrasound to noninvasively control cells genetically modified with ultrasound-sensitive ion channels, can be a powerful tool for investigating intact brain circuits. Here we show that TRPV1 is an ultrasound-sensitive ion channel that can modify the activity of TRPV1-expressing cells in vitro when exposing to focused ultrasound. We also show that focused ultrasound exposure at the mouse brain in vivo can selectively activate neurons that are genetically modified to express TRPV1. We demonstrate that precise manipulation of neural activity via TRPV1-based sonogenetics can be achieved by spatiotemporal control of ultrasound-induced heating. The focused ultrasound exposure is safe based on our inspection of neuronal integrity, apoptosis, and inflammation markers. This sonogenetic tool enables noninvasive, cell-type specific, spatiotemporally controlled modulation of mammalian brain activity.


2017 ◽  
Author(s):  
Zhiwei Ma ◽  
Nanyin Zhang

AbstractSpontaneous brain activity, typically investigated using resting-state fMRI (rsfMRI), provides a measure of inter-areal resting-state functional connectivity (RSFC). Previous rsfMRI studies mainly focused on spatial characteristics of RSFC, but the temporal relationship between RSFC patterns is still elusive. Particularly, it remains unknown whether separate RSFC patterns temporally fluctuate in a random manner, or transit in specific orders. Here we investigated temporal transitions between characteristic RSFC patterns in awake rats and humans. We found that transitions between RSFC patterns were reproducible and significantly above chance, suggesting that RSFC pattern transitions were nonrandom. The organization of RSFC pattern transitions in rats was analyzed using graph theory. Pivotal RSFC patterns in transitions were identified including hippocampal, thalamic and striatal networks. This study has revealed nonrandom temporal relationship between characteristic RSFC patterns in both rats and humans. It offers new insights into understanding the spatiotemporal dynamics of spontaneous activity in the mammalian brain.


2020 ◽  
Vol 11 ◽  
Author(s):  
Xiaoyun Liu ◽  
Zhenghua Hou ◽  
Yingying Yin ◽  
Chunming Xie ◽  
Haisan Zhang ◽  
...  

Objectives: This study aimed to examine the interactive effects of dopamine (DA) pathway gene and disease on spontaneous brain activity and further to explore the relationship between spontaneous brain activity and the early antidepressant therapeutic effect in patients with major depressive disorder (MDD).Methods: A total of 104 patients with MDD and 64 healthy controls (HCs) were recruited. The Hamilton Depression Scale-24 (HAMD-24) was used to measure the depression severity. Both groups were given resting-state functional magnetic resonance imaging (rs-fMRI) scan. The amplitude of low-frequency fluctuation (ALFF) was calculated to reflect the spontaneous brain activity based on the rs-fMRI data. After treatment for 2 weeks, depression severity was evaluated again, and HAMD-24 reductive rate was used to measure the therapeutic effect of antidepressants. Multilocus genetic profile scores (MGPS) were used to assess the multi-site cumulative effect of DA pathway gene. The interactive effects of MDD and DA pathway gene on the ALFF of regional brain areas were measured by the multivariate linear regression analysis. Finally, partial correlation analysis (age, sex, education, and illness durations as covariates) was performed to identify the relationship between regional ALFF and therapeutic effect.Results: MDD and DA-MGPS had interactive effects on the left fusiform gyrus (FG_L), right calcarine sulcus (CS_R), left superior temporal gyrus (STG_L), bilateral cerebellum posterior lobe (CPL), bilateral inferior frontal gyrus (IFG), and bilateral superior frontal gyrus (SFG). Partial correlation analysis revealed that the ALFF of STG_L had a significant negative correlation with 2-week HAMD-24 reductive rate (r = −0.211, P = 0.035).Conclusions: The spontaneous activity of STG_L may be a potential biomarker of antidepressant-related early therapeutic effect underlying the influence of DA pathway genes in MDD.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Weizhao Lu ◽  
Xueliang Yu ◽  
Lisheng Zhao ◽  
Yanli Zhang ◽  
Feng Zhao ◽  
...  

Purpose.Anisometropic amblyopia usually occurs during early childhood and results in monocular visual deficit. Recent neuroimaging studies have demonstrated structural and functional alterations in pediatric anisometropic amblyopia (PAA) patients. However, the relationship between structural and functional alterations remains largely unknown. The aim of this study was to investigate the relationship between structural and functional alterations in PAA patients. Materials and Methods. Eighteen PAA patients and 14 healthy children underwent a multimodal MRI scanning including T1WI and functional MRI (fMRI). Voxel-based morphometry was used to assess structural alterations between PAA patients and healthy children. Regional homogeneity (ReHo) was used to investigate changes in local spontaneous brain activity in the enrolled subjects. Correlations between structural, functional alterations, and clinical information were analyzed in the PAA group. Results. Compared with healthy children, PAA patients exhibited significantly reduced ReHo of spontaneous brain activity in the right superior temporal gyrus (STG) and right middle frontal gyrus (MFG) and increased gray matter volume in the right lobules 4 and 5 of the cerebellum. The gray matter volume of the right lobules 4 and 5 of the cerebellum was negatively correlated with the ReHo values of the right MFG. Conclusions. Our findings may suggest that PAA patients experience structural and functional abnormalities in brain regions related to oculomotor and visual-spatial information. In addition, the increased gray matter volume may compensate the decreased brain activity in the oculomotor regions, which reflects compensatory or neural plasticity in PAA patients.


2021 ◽  
Vol 15 ◽  
Author(s):  
Marc Rosenkranz ◽  
Björn Holtze ◽  
Manuela Jaeger ◽  
Stefan Debener

Several solutions have been proposed to study the relationship between ongoing brain activity and natural sensory stimuli, such as running speech. Computing the intersubject correlation (ISC) has been proposed as one possible approach. Previous evidence suggests that ISCs between the participants’ electroencephalogram (EEG) may be modulated by attention. The current study addressed this question in a competing-speaker paradigm, where participants (N = 41) had to attend to one of two concurrently presented speech streams. ISCs between participants’ EEG were higher for participants attending to the same story compared to participants attending to different stories. Furthermore, we found that ISCs between individual and group data predicted whether an individual attended to the left or right speech stream. Interestingly, the magnitude of the shared neural response with others attending to the same story was related to the individual neural representation of the attended and ignored speech envelope. Overall, our findings indicate that ISC differences reflect the magnitude of selective attentional engagement to speech.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eric Lacosse ◽  
Klaus Scheffler ◽  
Gabriele Lohmann ◽  
Georg Martius

AbstractCognitive fMRI research primarily relies on task-averaged responses over many subjects to describe general principles of brain function. Nonetheless, there exists a large variability between subjects that is also reflected in spontaneous brain activity as measured by resting state fMRI (rsfMRI). Leveraging this fact, several recent studies have therefore aimed at predicting task activation from rsfMRI using various machine learning methods within a growing literature on ‘connectome fingerprinting’. In reviewing these results, we found lack of an evaluation against robust baselines that reliably supports a novelty of predictions for this task. On closer examination to reported methods, we found most underperform against trivial baseline model performances based on massive group averaging when whole-cortex prediction is considered. Here we present a modification to published methods that remedies this problem to large extent. Our proposed modification is based on a single-vertex approach that replaces commonly used brain parcellations. We further provide a summary of this model evaluation by characterizing empirical properties of where prediction for this task appears possible, explaining why some predictions largely fail for certain targets. Finally, with these empirical observations we investigate whether individual prediction scores explain individual behavioral differences in a task.


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