Neuronal firing modulation by a membrane-targeted photoswitch

Area of Science:

• Neuroscience
• Biophysics
• Optical Engineering

Background:

• High spatio-temporal resolution optical control of neuronal activity is crucial in neuroscience.
• Azobenzene-based photoswitches offer nanoscale tools for neuronal photostimulation.

Purpose of the Study:

• To engineer a novel light-sensitive azobenzene compound (Ziapin2) for precise neuronal modulation.
• To investigate Ziapin2's mechanism of action on neuronal membrane capacitance and activity.

Main Methods:

• Engineered Ziapin2, a light-sensitive azobenzene compound.
• Studied Ziapin2's partitioning into the plasma membrane and its effect on membrane capacitance.
• Applied millisecond light pulses to neurons loaded with Ziapin2.
• Recorded neuronal responses including hyperpolarization, depolarization, and action potential firing.
• Assessed the persistence of Ziapin2 effects in vivo.

Main Results:

• Ziapin2 stably partitions into the plasma membrane, causing thinning and increased membrane capacitance in the dark.
• Millisecond light pulses induced transient hyperpolarization followed by delayed depolarization, triggering action potentials.
• Observed persistent effects in vivo for up to 7 days.
• Demonstrated modulation of membrane capacitance on the millisecond timescale without affecting ion channels or temperature.

Conclusions:

• Ziapin2 is a potent tool for optical control of neuronal activity via membrane capacitance modulation.
• The compound offers persistent, light-inducible neuronal stimulation with high spatio-temporal precision.
• Ziapin2 holds promise for advanced applications in neuroscience research and potential therapeutic interventions.