2022
Chemical Targeting of Rhodol Voltage-Sensitive Dyes to Dopaminergic Neurons
FIALA, Tomáš; Eugene V MOSHAROV; Jihang WANG; Adriana M MENDIETA; Se Joon CHOI et al.Základní údaje
Originální název
Chemical Targeting of Rhodol Voltage-Sensitive Dyes to Dopaminergic Neurons
Autoři
FIALA, Tomáš ORCID; Eugene V MOSHAROV; Jihang WANG; Adriana M MENDIETA; Se Joon CHOI; Eva FIALOVA; Christopher HWU; David SULZER a Dalibor SAMES
Vydání
ACS Chemical Neuroscience, WASHINGTON, American Chemical Society, 2022, 1948-7193
Další údaje
Typ výsledku
Článek v odborném periodiku
Utajení
není předmětem státního či obchodního tajemství
Impakt faktor
Impact factor: 5.000
Označené pro přenos do RIV
Ne
Klíčová slova anglicky
voltage-sensitive dyes; chemical targeting; cell type-specific; maging; molecular; maging probes
Změněno: 17. 2. 2025 10:33, Mgr. Pavla Foltynová, Ph.D.
Anotace
V originále
Optical imaging of changes in the membrane potential of living cells can be achieved by means of fluorescent voltage-sensitive dyes (VSDs). A particularly challenging task is to efficiently deliver these highly lipophilic probes to specific neuronal subpopulations in brain tissue. We have tackled this task by designing a solubilizing, hydrophilic polymer platform that carries a high-affinity ligand for a membrane protein marker of interest and a fluorescent VSD. Here, we disclose an improved design of polymer-supported probes for chemical, nongenetic targeting of voltage sensors to axons natively expressing the dopamine transporter in ex vivo mouse brain tissue. We first show that for negatively charged rhodol VSDs functioning on the photoinduced electron transfer principle, poly(ethylene glycol) as a carrier enables targeting with higher selectivity than the polysaccharide dextran in HEK cell culture. In the same experimental setting, we also demonstrate that incorporation of an azetidine ring into the rhodol chromophore substantially increases the brightness and voltage sensitivity of the respective VSD. We show that the superior properties of the optimized sensor are transferable to recording of electrically evoked activity from dopaminergic axons in mouse striatal slices after averaging of multiple trials. Finally, we suggest the next milestones for the field to achieve single-scan recordings with nongenetically targeted VSDs in native brain tissue.