A Chemically Tailorable Multifunctional Protein Platform for Glutamatergic Neuron Targeting in Mouse Brain.

Area of Science:

• Neuroscience
• Molecular Biology
• Biotechnology

Background:

• Targeting glutamatergic neurons is crucial for neuroscience research and treating neurological disorders.
• Existing methods for targeting these neurons have limitations, including poor blood-brain barrier penetration and reliance on transgenic approaches.

Purpose of the Study:

• To introduce a novel, non-transgenic platform for rapid and selective targeting of glutamatergic neurons in vivo.
• To demonstrate the platform's capability for in vivo imaging and neuromodulation of these neurons.

Main Methods:

• Utilized cyanobacterial ferredoxin-dependent glutamate synthase (Fd-GOGATcb) for its affinity to glutamatergic neuron membranes.
• Demonstrated blood-brain barrier penetration and rapid, fixation-free labeling.
• Conjugated Fd-GOGATcb with functional motifs (fluorophores, photosensitizers) for targeted applications.

Main Results:

• Fd-GOGATcb exhibits high affinity for glutamatergic neuron membranes, enabling quick labeling (1-2 hours).
• The platform demonstrates self-deliverable blood-brain barrier crossing via systemic administration in mice.
• Targeted in vivo imaging and light-responsive neuron inhibition were achieved through Fd-GOGATcb conjugates.

Conclusions:

• The Fd-GOGATcb platform offers a non-transgenic, efficient solution for targeting glutamatergic neurons in vivo.
• This approach overcomes significant barriers in neuron targeting and manipulation, with potential for fundamental research and clinical translation.
• The platform's adaptability through chemical functionalization opens versatile applications in glutamate-centered neuroscience.