J 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

Štítky

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.