Multimodal fast optical interrogation of neural circuitry

Area of Science:

• Neuroscience
• Optogenetics
• Molecular Biology

Background:

• Understanding neural circuits requires tools to precisely control specific neuron activity.
• Existing optogenetic tools primarily focus on excitation, limiting bidirectional control.

Purpose of the Study:

• To identify and develop a novel optogenetic tool for the precise inhibition of neural activity.
• To create a complementary tool to existing excitation technologies for all-optical interrogation of neural circuits.

Main Methods:

• Identification and characterization of an archaeal light-driven chloride pump (NpHR) from Natronomonas pharaonis.
• Testing NpHR's efficacy in inhibiting neural activity in mammalian brain tissue and Caenorhabditis elegans.
• Integration of NpHR with Channelrhodopsin-2 (ChR2) for bidirectional optical control.

Main Results:

• NpHR enables temporally precise optical inhibition of neural activity, including knockout of single action potentials and sustained spiking blockade.
• NpHR functions effectively in mammals without exogenous cofactors.
• NpHR and ChR2 can be combined for bidirectional optical modulation and readout of neural activity in mammalian brain tissue and control of locomotion in C. elegans.

Conclusions:

• NpHR represents a significant advancement in optogenetic tools for neural circuit interrogation.
• The combination of NpHR and ChR2 provides a complete system for multimodal, high-speed, genetically targeted, all-optical control of living neural circuits.