scholarly journals Non-invasive, opsin-free mid-infrared modulation activates cortical neurons and accelerates associative learning

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jianxiong Zhang ◽  
Yong He ◽  
Shanshan Liang ◽  
Xiang Liao ◽  
Tong Li ◽  
...  

AbstractNeurostimulant drugs or magnetic/electrical stimulation techniques can overcome attention deficits, but these drugs or techniques are weakly beneficial in boosting the learning capabilities of healthy subjects. Here, we report a stimulation technique, mid-infrared modulation (MIM), that delivers mid-infrared light energy through the opened skull or even non-invasively through a thinned intact skull and can activate brain neurons in vivo without introducing any exogeneous gene. Using c-Fos immunohistochemistry, in vivo single-cell electrophysiology and two-photon Ca2+ imaging in mice, we demonstrate that MIM significantly induces firing activities of neurons in the targeted cortical area. Moreover, mice that receive MIM targeting to the auditory cortex during an auditory associative learning task exhibit a faster learning speed (~50% faster) than control mice. Together, this non-invasive, opsin-free MIM technique is demonstrated with potential for modulating neuronal activity.

2020 ◽  
Author(s):  
Xiaowei Chen ◽  
Jianxiong Zhang ◽  
Yong He ◽  
Shanshan Liang ◽  
Xiang Liao ◽  
...  

Abstract Boosting learning capability represents a long-sought dream of mankind. Neurostimulant drugs or magnetic/electrical stimulation techniques can overcome attention deficits, but these drugs or techniques are weakly beneficial in boosting the learning capabilities of healthy subjects. Here, we report a stimulation technique, mid-infrared modulation (MIM), that delivers mid-infrared light energy through opened skull or even non-invasively through thinned intact skull and can activate brain neurons in vivo without introducing any exogeneous gene. Using c-Fos immunohistochemistry, in vivo single-cell electrophysiology and two-photon Ca2+ imaging in mice, we demonstrate that MIM significantly induces firing activities of neurons in the targeted cortical area. Moreover, mice that receive MIM targeting to the auditory cortex during an auditory associative learning task exhibit a strikingly faster learning speed (~ 50% faster) than control mice. Together, this non-invasive, opsin-free MIM technique is demonstrated with a great translational potential for activating brain neurons and boosting brain learning capability.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Markus Seeger ◽  
Christoph Dehner ◽  
Dominik Jüstel ◽  
Vasilis Ntziachristos

AbstractThe non-invasive investigation of multiple biological processes remains a methodological challenge as it requires capturing different contrast mechanisms, usually not available with any single modality. Intravital microscopy has played a key role in dynamically studying biological morphology and function, but it is generally limited to resolving a small number of contrasts, typically generated by the use of transgenic labels, disturbing the biological system. We introduce concurrent 5-modal microscopy (Co5M), illustrating a new concept for label-free in vivo observations by simultaneously capturing optoacoustic, two-photon excitation fluorescence, second and third harmonic generation, and brightfield contrast. We apply Co5M to non-invasively visualize multiple wound healing biomarkers and quantitatively monitor a number of processes and features, including longitudinal changes in wound shape, microvascular and collagen density, vessel size and fractality, and the plasticity of sebaceous glands. Analysis of these parameters offers unique insights into the interplay of wound closure, vasodilation, angiogenesis, skin contracture, and epithelial reformation in space and time, inaccessible by other methods. Co5M challenges the conventional concept of biological observation by yielding multiple simultaneous parameters of pathophysiological processes in a label-free mode.


2020 ◽  
Vol 6 (44) ◽  
pp. eabb6165
Author(s):  
Lukas Pfeifer ◽  
Nong V. Hoang ◽  
Maximilian Scherübl ◽  
Maxim S. Pshenichnikov ◽  
Ben L. Feringa

Light-controlled artificial molecular machines hold tremendous potential to revolutionize molecular sciences as autonomous motion allows the design of smart materials and systems whose properties can respond, adapt, and be modified on command. One long-standing challenge toward future applicability has been the need to develop methods using low-energy, low-intensity, near-infrared light to power these nanomachines. Here, we describe a rotary molecular motor sensitized by a two-photon absorber, which efficiently operates under near-infrared light at intensities and wavelengths compatible with in vivo studies. Time-resolved spectroscopy was used to gain insight into the mechanism of energy transfer to the motor following initial two-photon excitation. Our results offer prospects toward in vitro and in vivo applications of artificial molecular motors.


Author(s):  
Vania Y. Cao ◽  
Yizhou Ye ◽  
Surjeet S. Mastwal ◽  
David M. Lovinger ◽  
Rui M. Costa ◽  
...  

2020 ◽  
Author(s):  
Sonja Blumenstock ◽  
Fanfan Sun ◽  
Petar Marinković ◽  
Carmelo Sgobio ◽  
Sabine Liebscher ◽  
...  

SummaryAlpha-synucleinopathies are characterized by self-aggregation of the protein alpha-synuclein (a-syn), causing alterations on the molecular and cellular level. To unravel the impact of transneuronal spreading and templated misfolding of a-syn on the microcircuitry of remotely connected brain areas, we investigated cortical neuron function in awake mice 9 months after a single intrastriatal injection of a-syn preformed fibrils (PFFs), using in vivo two-photon calcium imaging. We found altered function of layer 2/3 cortical neurons in somatosensory cortex (S1) of PFF-inoculated mice, as witnessed by an enhanced response to whisking and increased synchrony, accompanied by a decrease in baseline Ca2+ levels. Stereological analyses revealed a reduction in GAD67-positive inhibitory cells in S1 in PFF-injected brains. These findings point to a disturbed excitation/inhibition balance as an important pathomechanism in alpha-synucleinopathies and demonstrate a clear association between the spread of toxic proteins and the initiation of altered neuronal function in remotely connected areas.


2014 ◽  
Vol 5 (7) ◽  
pp. 2397 ◽  
Author(s):  
Sabbir Liakat ◽  
Kevin A. Bors ◽  
Laura Xu ◽  
Callie M. Woods ◽  
Jessica Doyle ◽  
...  

2008 ◽  
Author(s):  
Iris Riemann ◽  
Alexander Ehlers ◽  
Ronan Le Harzic ◽  
Enrico Dimitrow ◽  
Martin Kaatz ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marius Kröger ◽  
Jörg Scheffel ◽  
Viktor V. Nikolaev ◽  
Evgeny A. Shirshin ◽  
Frank Siebenhaar ◽  
...  

Abstract Mast cells (MCs) are multifunctional cells of the immune system and are found in skin and all major tissues of the body. They contribute to the pathology of several diseases including urticaria, psoriasis, atopic dermatitis and mastocytosis where they are increased at lesional sites. Histomorphometric analysis of skin biopsies serves as a routine method for the assessment of MC numbers and their activation status, which comes with major limitations. As of now, non-invasive techniques to study MCs in vivo are not available. Here, we describe a label-free imaging technique to visualize MCs and their activation status in the human papillary dermis in vivo. This technique uses two-photon excited fluorescence lifetime imaging (TPE-FLIM) signatures, which are different for MCs and other dermal components. TPE-FLIM allows for the visualization and quantification of dermal MCs in healthy subjects and patients with skin diseases. Moreover, TPE-FLIM can differentiate between two MC populations in the papillary dermis in vivo—resting and activated MCs with a sensitivity of 0.81 and 0.87 and a specificity of 0.85 and 0.84, respectively. Results obtained on healthy volunteers and allergy and mastocytosis patients indicate the existence of other MC subpopulations within known resting and activated MC populations. The developed method may become an important tool for non-invasive in vivo diagnostics and therapy control in dermatology and immunology, which will help to better understand pathomechanisms involving MC accumulation, activation and degranulation and to characterize the effects of therapies that target MCs.


eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Balázs B Ujfalussy ◽  
Judit K Makara ◽  
Tiago Branco ◽  
Máté Lengyel

Cortical neurons integrate thousands of synaptic inputs in their dendrites in highly nonlinear ways. It is unknown how these dendritic nonlinearities in individual cells contribute to computations at the level of neural circuits. Here, we show that dendritic nonlinearities are critical for the efficient integration of synaptic inputs in circuits performing analog computations with spiking neurons. We developed a theory that formalizes how a neuron's dendritic nonlinearity that is optimal for integrating synaptic inputs depends on the statistics of its presynaptic activity patterns. Based on their in vivo preynaptic population statistics (firing rates, membrane potential fluctuations, and correlations due to ensemble dynamics), our theory accurately predicted the responses of two different types of cortical pyramidal cells to patterned stimulation by two-photon glutamate uncaging. These results reveal a new computational principle underlying dendritic integration in cortical neurons by suggesting a functional link between cellular and systems--level properties of cortical circuits.


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