Nonsurgical Control of Seizure Threshold with Acoustically Targeted Chemogenetics

Area of Science:

• Neuroscience
• Biotechnology
• Medical Devices

Background:

• Neurological and psychiatric diseases often involve pathological neuronal activity.
• Current treatments lack nonsurgical, site-, and cell-type specificity.
• There is a need for precise, non-invasive neuromodulation techniques.

Purpose of the Study:

• To investigate Acoustically-Targeted Chemogenetics (ATAC) as a nonsurgical method to increase seizure threshold.
• To achieve site- and cell-type specific neuronal inhibition in the hippocampus.
• To evaluate the efficacy of ATAC compared to existing treatments.

Main Methods:

• Applied multipoint focused ultrasound to transiently open the blood-brain barrier in the mouse hippocampus.
• Utilized a viral vector (AAV.FUS.3) for ultrasound-based gene delivery of engineered G-protein-coupled receptors.
• Administered ATAC to transduce and inhibit pyramidal neuron activity in a mouse seizure model.

Main Results:

• Demonstrated successful gene delivery throughout the hippocampus using the ATAC approach.
• Observed significant inhibition of neuronal activity, evidenced by an increased seizure threshold.
• Showcased ATAC's precision compared to a non-spatially specific clinical drug.

Conclusions:

• ATAC is a viable nonsurgical neuromodulation strategy for increasing seizure threshold.
• The technique offers precise targeting of hippocampal pyramidal neurons.
• ATAC represents a significant advancement over current non-specific treatments for neurological disorders.