Chenchen Song's research while affiliated with Imperial College London and other places

Publications (34)

Article
Full-text available
DNA methylation profiling has become a promising approach towards identifying biomarkers of neuropsychiatric disorders including autism spectrum disorder (ASD). Epigenetic markers capture genetic risk factors and diverse exogenous and endogenous factors, including environmental risk factors and complex disease pathologies. We analysed the different...
Article
Full-text available
A new generation of optogenetic tools for analyzing neural activity has been contributing to the elucidation of classical open questions in neuroscience. Specifically, voltage imaging technologies using enhanced genetically encoded voltage indicators have been increasingly used to observe the dynamics of large circuits at the mesoscale. Here, we de...
Article
Full-text available
Foreword from the editors. We hosted four keynote speakers: Wolf Singer, Bill Bialek, Danielle Bassett, and Sonja Gruen. They enlightened us about computations in the cerebral cortex, the reduction of high-dimensional data, the emerging field of computational psychiatry, and the significance of spike patterns in motor cortex. From the submissions,...
Article
Full-text available
Cortical circuits generate patterned activities that reflect intrinsic brain dynamics that lay the foundation for any, including stimuli-evoked, cognition and behavior. However, the spatiotemporal organization properties and principles of this intrinsic activity have only been partially elucidated because of previous poor resolution of experimental...
Chapter
Optogenetic approaches combine the power to allocate optogenetic tools (proteins) to specific cell populations (defined genetically or functionally) and the use of light-based interfaces between biological wetware (cells and tissues) and hardware (controllers and recorders). The optogenetic toolbox contains two main compartments: tools to interfere...
Conference Paper
A system for quasi-simultaneous direct recording from multiple neurons is presented. A digital micromirror device (DMD) is used to selectively illuminate specific neurons, switching between them at high speed to isolate voltage signals. © 2021 The Author(s)
Article
We developed genetically encoded voltage indicators using a transmembrane voltage-sensing domain and bright near-infrared fluorescent proteins derived from bacterial phytochromes. These new voltage indicators are excited by 640 nm light and emission is measured at 670 nm, allowing imaging in the near-infrared tissue transparency window. The spectra...
Preprint
Full-text available
Autism spectrum disorder (ASD) is characterized by core deficits in social interaction. The classic serotonergic psychedelic psilocybin has been suggested as a therapeutic agent that may ameliorate in the core symptomology of ASD. We found that the acute response to psilocybin was attenuated in the prenatal valproic acid exposure mouse model of ASD...
Article
Full-text available
Significance: Light-field microscopy (LFM) enables high signal-to-noise ratio (SNR) and light efficient volume imaging at fast frame rates. Voltage imaging with genetically encoded voltage indicators (GEVIs) stands to particularly benefit from LFM's volumetric imaging capability due to high required sampling rates and limited probe brightness and f...
Preprint
Full-text available
Light field microscopy (LFM) enables high signal-to-noise ratio (SNR), light efficient volume imaging at fast frame rates, and has been successfully applied to single-cell resolution functional neuronal calcium imaging. Voltage imaging with genetically encoded voltage indicators (GEVIs) stands to particularly benefit from light field microscopy's v...
Conference Paper
An improved method for the optical readout of voltage indicators is presented, whereby fluorescence from the whole surface of a neuron is integrated onto a single detector, dramatically increasing the recording bandwidth over conventional techniques.
Article
A central goal in neuroscience is to determine how the brain’s neuronal circuits generate perception, cognition and emotions and how these lead to appropriate behavioural actions. A methodological platform based on genetically encoded voltage indicators (GEVIs) that enables the monitoring of large-scale circuit dynamics has brought us closer to thi...
Article
Fluorescent probes that indicate biologically important quantities are widely used for many different types of biological experiments across life sciences. During recent years, limitations of small molecule-based indicators have been overcome by the development of genetically encoded indicators. Here we focus on fluorescent calcium and voltage indi...
Article
Full-text available
Brain signaling occurs across a wide range of spatial and temporal scales, and analysis of brain signal variability and synchrony has attracted recent attention as markers of intelligence, cognitive states, and brain disorders. However, current technologies to measure brain signals in humans have limited resolutions either in space or in time and c...
Article
Full-text available
Voltage imaging of many neurons simultaneously at single-cell resolution is hampered by the difficulty of detecting small voltage signals from overlapping neuronal processes in neural tissue. Recent advances in genetically encoded voltage indicator (GEVI) imaging have shown single-cell resolution optical voltage recordings in intact tissue through...
Preprint
We developed genetically encoded voltage indicators (GEVIs) using bright near-infrared (NIR) fluorescent proteins from bacterial phytochromes. These new NIR GEVIs are optimized for combination of voltage imaging with simultaneous blue light optogenetic actuator activation. Iterative optimizations led to a GEVI here termed nirButterfly, which reliab...
Article
Full-text available
Sensory inputs carry critical information for the survival of an organism. In mice, tactile information conveyed by the whiskers is of high behavioural relevance, and is broadcasted across cortical areas beyond the primary somatosensory cortex. Mesoscopic voltage sensitive dye imaging (VSDI) of cortical population response to whisker stimulations h...
Article
Full-text available
Rapidly progressing development of optogenetic tools, particularly genetically encoded optical indicators, enables monitoring activities of neuronal circuits of identified cell populations in longitudinal in vivo studies. Recently developed advanced transgenic approaches achieve high levels of indicator expression. However, targeting non-sparse cel...
Article
Full-text available
The pioneering work of Amiram Grinvald established voltage-sensitive dye imaging (VSDI) in the mammalian cortex in the 1980s and inspired decades of cortical voltage imaging and the associated technological developments. The recent conception and development of genetically encoded voltage indicators (GEVIs) overcome many of the limitations of class...
Article
Full-text available
Slow cortical waves that propagate across the cerebral cortex forming large-scale spatiotemporal propagation patterns are a hallmark of non-REM sleep and anesthesia, but also occur during resting wakefulness. To investigate how the spatial temporal properties of slow waves change with the depth of anesthetic, we optically imaged population voltage...
Article
The flow of information through networks of cortical neurons is thought to provide the processing power that underpins cognition. Traditional structural methods to map connectivity are blind to the functional dynamics of cortical circuits. Emerging approaches use genetically encoded activity indicators such as GCaMP. However they are limited to rep...
Article
Full-text available
Some neural circuits operate with simple dynamics characterized by one or a few well-defined spatiotemporal scales (e.g. central pattern generators). In contrast, cortical neuronal networks often exhibit richer activity patterns in which all spatiotemporal scales are represented. Such “scale-free” cortical dynamics manifest as cascades of activity...
Article
Full-text available
Optogenetics - the use of light and genetics to manipulate and monitor the activities of defined cell populations - has already had a transformative impact on basic neuroscience research. Now, the conceptual and methodological advances associated with optogenetic approaches are providing fresh momentum to neuroscience drug discovery, particularly i...
Article
Electrical signals are fundamental to cellular sensing, communication and motility. In the nervous system, information is represented as receptor, synaptic and action potentials. Understanding how brain functions emerge from these electrical signals is one of the ultimate challenges in neuroscience and requires a methodology to monitor membrane vol...
Article
The invention of membrane voltage protein indicators widens the reach of optical voltage imaging in cell physiology, most notably neurophysiology, by enabling membrane voltage recordings from genetically defined cell types in chronic and life-long preparations. While the last years have seen a dramatic improvement in the technical performance of th...
Article
Full-text available
Deciphering how the brain generates cognitive function from patterns of electrical signals is one of the ultimate challenges in neuroscience. To this end, it would be highly desirable to monitor the activities of very large numbers of neurons while an animal engages in complex behaviors. Optical imaging of electrical activity using genetically enco...

Citations

... After the surgery all animals were given at least 3 days before beginning the habituation in the setup. See (Pedrosa and Battaglia, 2021) for a detailed description of the protocol. ...
... The properties that are typically reported are thus often heuristic and include, for example, transition slopes (Chan et al., 2015), b) recorded anesthetized GCaMP6f mice with wide-field fluorescence microscopy (Celotto et al., 2020), c) distributed network of cortical columns of LIF with Spike Frequency Adaptation neurons (Pastorelli et al., 2019), d) one-dimensional multi-layer thalamo-cortical model with one-and two-compartment neuron models using Hodgkin-Huxley kinetics (Bazhenov et al., 2002), e) 2D balanced conductance-based spiking neural network model (Keane and Gong, 2015), f) multi-electrode recording in ferret cortical slices (Capone et al., 2019b), g) human HD-EEG during first sleep episode of the night (Massimini et al., 2004), h) human ECoG recording during sleep (Muller et al., 2016), i) intracranial depth EEG in sleeping human subjects , j) intracranial depth EEG in humans during sleep (Botella-Soler et al., 2012). (Ruiz-Mejias et al., 2011), phase velocity (Massimini et al., 2004;Muller et al., 2016), wave type classification Denker et al., 2018b;Pazienti et al., 2022;Roberts et al., 2019;Townsend et al., 2015), source/sink location and propagation patterns (Huang et al., 2010;Liang et al., 2021), excitability (De Bonis et al., 2019;Mattia and Sanchez-Vives, 2012;Ruiz-Mejias et al., 2016), event frequency (Capone et al., 2022), and others. Thus, we here also focus on such common observables (i.e., planarity, inter-wave intervals, velocity, and direction). ...
... Although the abovementioned approaches can all be combined with Ca 2+ signaling networks, it is worth noting that other relevant signals can be assessed. Imaging of islet cell membrane potential has been accomplished using small molecule voltage-sensitive probes (289), and may perhaps be more robustly measured using newer genetically encoded voltage indicators (290). Moreover, optogenetic control of islet function is also feasible in transgenic models (291). ...
... Therefore, current experimental approaches to detect membrane protein activation are often based on detecting conformational changes or translocation of proteins [22]. For example, Monakhov et al. constructed a cell-based sensor that can detect membrane polarization using a synthetic voltage-sensitive domain derived from a voltage-sensitive phosphatase (VSP) isolated from the tunicate Ciona intestinalis ( Figure 1A) [29]. The sensor protein was designed by introducing a FRET donor and acceptor at each terminus of a synthetic voltage gate protein, in which conformational changes of the protein in the polarized membrane bring the N-and C-terminus of the protein into proximity to activate the FRET signal. ...
... To exclude acute psychedelic effects, the authors performed sociability and social memory behavioral tests after 24 h following administration of psilocybin. The results showed that psilocybin ameliorate the social behavioral abnormalities in the autism model mice [71]. In addition, treatment of 5-HT2CR antagonist SB242084 (Table 2) in the ASD risk gene Pten haploinsufficient mice rescued the social behavior deficits [72], whereas one research reported that SB242084 did not enhance strategy switching [67]. ...
... mammalian brain tissue, the sample is highly scattering, nontransparent and contains high background noise, which makes training artificial neural networks (ANN) challenging. On the other hand, model-based optimization approaches have shown to be more robust under these adverse experimental conditions [12], [13]. This work proposes a novel multimodal imaging approach leveraging the respective strengths of 2P microscopy and LFM. ...
... GECIs' main limit for real-time communication and neuroprosthetics is mainly represented by their intrinsic slow dynamics related to the intracellular calcium variations with consequent difficulty in reaching single action potential resolution [87][88][89]. GEVIs have been later introduced and represent the cutting edge of optical neural firing recording for neuroprosthetics, guaranteeing fast resolution (single action potentials) of neural firing, although with a lower signal-to-noise ratio compared to GECIs [90]. The challenges in relation to the application of GEVIs in real-time communication are mostly related to the interface and fast pre-processing of signals acquired, possibly with high-speed CMOS cameras [90]. ...
... The study of neuromodulation in the context of intact circuits is greatly facilitated by non-invasive imaging techniques. Ca 2+ imaging is a powerful and widely used approach (Patriarchi et al., 2018;Corkrum et al., 2020;Redolfi et al., 2021) and, thus far, preferred over fluorescent voltage indicators due to superior sensitivity, kinetics, and ease of expression (Vogt, 2015;Inagaki and Nagai, 2016;Mollinedo-Gajate et al., 2019;Inoue, 2021;Zhu et al., 2021). Ca 2+ imaging utilizes fluorescent calcium indicators, often encoded by transgenes with neuron specific promoters, enabling selective labeling in nervous system areas with high cellular heterogeneity. ...
... The multiscale dynamics of resting-state BOLD fluctuations are thus complex, which provides key information on neurophysiological regulations (Yang et al., 2015). Studies have emerged to characterize such complex dynamics by using multiscale entropy (MSE) and have demonstrated that resting-state BOLD complexity is closely associated with important functional performance (Liu et al., 2019;Zhou et al., 2020). Here, we also used MSE to characterize the complexity of BOLD fluctuation in each ROI. ...
... We used the patch-clamp electrode to manipulate the membrane potential of the recorded neurons and simultaneously recorded the fluorescence changes of Voltron-JF525-HTL using the SPAD sensor. In sparsely labelled preparations, [17] we observe fluorescence concentrated to the membrane of the soma of neurons expressing the soma-targeted Voltron-JF525-HTL ( Figures 1C and A). For post-processing, the region of interest (ROI) was selected manually and a binary mask was applied to the ROI, allowing isolation of the fluorescence-positive pixels within the ROI and from which we obtained the time-dependent traces from each neuron (Figure 2). ...