Neuronal firing modulation by a membrane-targeted photoswitch

DiFrancesco, Mattia L.; Lodola, Francesco; Colombo, Elisabetta; Maragliano, Luca; Bramini, Mattia; Paternò, Giuseppe M.; Baldelli, Pietro; Serra, Mauro Dalla; Lunelli, Lorenzo; Marchioretto, Marta; Grasselli, Giorgio; Cimò, Simone; Colella, Letizia; Fazzi, Daniele; Ortica, F.; Vurro, Vito; Eleftheriou, Cyril G.; Shmal, Dmytro; Maya‐Vetencourt, José Fernando; Bertarelli, Chiara; Lanzani, Guglielmo; Benfenati, Fabio

doi:10.1038/s41565-019-0632-6

Cited by 76 publications

(132 citation statements)

References 48 publications

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“…By modifying the surfactant, the photocontrolled release of Sulforhodamine B is possible, but in this case the vesicles need to be pre‐formed with the surfactant [13] . Recently, the groups of Lanzani and Benfenati integrated azobenzene containing molecules into a membrane, which causes thinning in their trans configuration leading to an increased membrane capacitance [14] …”

Section: Figurementioning

confidence: 99%

Photoswitchable Conjugated Oligoelectrolytes for a Light‐Induced Change of Membrane Morphology

et al. 2020

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The synthesis of a new conjugated oligoelectrolyte (COE), namely DSAzB, is described, which contains a conjugated core bearing a diazene moiety in the center of its electronically delocalized structure. Similar to structurally related phenylenevinylene-based COEs, DSAzB readily intercalates into model and natural lipid bilayer membranes. Photoinduced isomerization transforms the linear trans COE into a bent or C-shape form. It is thereby possible to introduce DSAzB into the bilayer of a cell and disrupt its integrity by irradiation with light. This leads to controlled permeabilization of membranes, as demonstrated by the release of calcein from DMPG/DMPC vesicles and by propidium iodide influx experiments on S. epidermidis. Both experiments support that the permeabilization is selective for the light stimulus, highly efficient, and repeatable. Target-selective and photoinduced actions demonstrated by DSAzB may have broad applications in biocatalysis and related biotechnologies.

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Section: Figurementioning

confidence: 99%

Photoswitchable Conjugated Oligoelectrolytes for a Light‐Induced Change of Membrane Morphology

et al. 2020

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“…On one side, there is an increasingly clear understanding of the body-brain system as a multidimensional network 5 where the neuronal electrical transmission sustains the communication among different nodes, in turn interacting with the functionality of the system at multiple levels (immune, behavioural and hormonal) 6,7 . On the other side, there is an acknowledgement that it is possible to communicate more effectively and by means of increasingly miniaturized and skilled devices with the body-brain network also by sending appropriate signals directly to some speci c nodes of the control network, strengthening bridges where communication has gone depleted due to a pathological condition 8,9 . A relevant branch of electroceuticals is the non-invasive brain stimulation (NIBS), where the two main techniques are repetitive transcranial magnetic stimulation (rTMS) 10 and transcranial direct current stimulation (tDCS) 11 .…”

Section: Introductionmentioning

confidence: 99%

tDCS Randomized Controlled Trials in No-structural Diseases: A Quantitative Review

Gianni

Bertoli

Simonelli

et al. 2021

Preprint

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The increasing number and quality of randomized controlled trials (RCTs) employing transcranial direct current stimulation (tDCS) denote the rising awareness of neuroscientific community about its electroceutical potential and opening to include these treatments in the framework of medical therapies under the indications of the international authorities.The purpose of this quantitative review is to estimate the recommendation strength applying the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria and PICO (population, intervention, comparison, outcome) model values for effective tDCS treatments on no-structural diseases, and to provide an estimate of Sham effect for future RCTs. Applying GRADE evaluation pathway, we searched in literature the tDCS-based RCTs in psychophysical diseases displaying a major involvement of brain electrical activity unbalances. Three independent authors agreed on Class 1 RCTs (18 studies) and meta-analyses were carried out using a random-effects model for pathologies sub-selected based on PICO and systemic involvement criteria. The meta-analysis integrated with extensive evidence of negligible side effects and low-cost, easy-to-use procedures, indicated that tDCS treatments for depression and fatigue in MS ranked between moderately and highly recommendable. For these interventions we reported the PICO variables, with left vs. right dorsolateral prefrontal target for 30 min/10 days against depression and bilateral somatosensory vs occipital target for 15min/5 days against MS fatigue.An across-diseases meta-analysis devoted to the Sham effect provided references for power analysis in future tDCS RCTs on these clinical conditions.High-quality indications support tDCS as a promising tool to build electroceutical treatments against diseases involving neurodynamics alterations.

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“…Termed photopharmacology, 8 this approach has been applied to manipulate ion channels, G protein-coupled receptors (GPCRs), enzymes, components of the cytoskeleton, and even cellular membranes. 6,[9][10][11][12][13][14] These photoswitchable small molecules can target endogenous receptors, or alternatively, genetically inserted exogenous proteins to create a wide variety of signaling events. Unfortunately, the utility of photopharmacology for studying mammalian behavior has been hindered by the lack of available hardware for delivering the chemical probes and optical stimuli to non-superficial brain regions.…”

Section: Introductionmentioning

confidence: 99%

In vivo photopharmacology enabled by multifunctional fibers

Frank

Antonini

Chiang

et al. 2020

Preprint

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To reversibly manipulate neural circuits with increased spatial and temporal control, photoswitchable ligands can add an optical switch to a target receptor or signaling cascade. This approach, termed photopharmacology, has been enabling to molecular neuroscience, however, its application to behavioral experiments has been impeded by a lack of integrated hardware capable of delivering both light and compounds to deep brain regions in moving subjects. Here, we devise a hybrid photochemical genetic approach to target neurons using a photoswitchable agonist of capsaicin receptor (TRPV1), red-AzCA-4. Using the thermal drawing process we created multifunctional fibers that can deliver viruses, photoswitchable ligands, and light to deep brain regions in awake, freely moving mice. We implanted our fibers into the ventral tegmental area (VTA), a midbrain hub of the mesolimbic pathway, and used them to deliver a transgene coding for TRPV1. This sensitized excitatory VTA neurons to red-AzCA-4, and allowed us to optically control conditioned place preference using a mammalian ion-channel, thus extending applications of photopharmacology to behavioral experiments. Applied to endogenous receptors, our approach may accelerate studies of molecular mechanisms underlying animal behavior. AUTHOR CONTRIBUTIONS JAF and PA conceived and coordinated the study. DBK synthesized the photoswitchable compounds. JAF and GR carried out imaging experiments in cultured neurons. JAF, MJA, and IG fabricated and characterized the multifunctional fibers. YF aided in fiber design. PC and FK produced lentiviral vectors. JAF, MJA, PC, AC, and IG performed immunohistochemical experiments. JAF and MJA performed the behavioral experiments. PC, AC, MJA, and JAF wrote scripts for data analysis. JAF, MJA, and PA wrote the manuscript with input from all co-authors.

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Neuronal firing modulation by a membrane-targeted photoswitch

Cited by 76 publications

References 48 publications

Photoswitchable Conjugated Oligoelectrolytes for a Light‐Induced Change of Membrane Morphology

Photoswitchable Conjugated Oligoelectrolytes for a Light‐Induced Change of Membrane Morphology

tDCS Randomized Controlled Trials in No-structural Diseases: A Quantitative Review

In vivo photopharmacology enabled by multifunctional fibers

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Neuronal firing modulation by a membrane-targeted photoswitch

Cited by 76 publications

References 48 publications

Photoswitchable Conjugated Oligoelectrolytes for a Light‐Induced Change of Membrane Morphology

Photoswitchable Conjugated Oligoelectrolytes for a Light‐Induced Change of Membrane Morphology

tDCS&nbsp;Randomized Controlled Trials in No-structural Diseases:&nbsp;A Quantitative Review

In vivo photopharmacology enabled by multifunctional fibers

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tDCS Randomized Controlled Trials in No-structural Diseases: A Quantitative Review