Optogenetic magnetic resonance imaging
View Patent ↗Disclosed herein are systems and methods involving the use of magnetic resonance imaging and optogenetic neural stimulation. Aspects of the disclosure include modifying a target neural cell population in a first region of a brain to express light-responsive molecules. Using a light pulse, the light-responsive molecules in the target neural cell population are stimulated. Multiple regions of the brain are scanned via magnetic resonance imaging. The scans allow for observation of a neural reaction in response to the stimulation in at least one of the multiple regions of the brain.
1. A method comprising:
modifying a target neural cell population in a first region of a brain to express a light-responsive opsin polypeptide;
stimulating, using a light pulse, a second region of the brain not modified to express the light-responsive opsin polypeptide;
scanning multiple regions of the brain via functional magnetic resonance imaging (fMRI) to observe a neural reaction in response to the stimulation in the second region of the brain; and
determining whether neural projections in the second region of the brain are connected to at least some of the modified target cell population in the first region of the brain.
2. The method of claim 1 , further comprising determining whether neural projections in the first region of the brain are connected to neural cells in the second region of the brain.
3. The method of claim 1 , wherein the stimulating is performed at a first light pulse rate and a second light pulse rate.
4. The method of claim 3 , wherein results of the stimulating at the first light pulse rate and the second light pulse rate are combined, and the method comprises providing a functional map of the brain including at least the results of the stimulating at the first light pulse rate and the second light pulse rate.
5. The method of claim 1 , wherein the first region of the brain is in the motor cortex.
6. The method of claim 1 , wherein the second region of the brain is in the thalamus.
7. The method of claim 1 , wherein the observed neural reactions are used to determine a treatment plan for a disease affecting at least one of the first or second regions of the brain.
8. The method of claim 1 , further comprising:
introducing a drug into the brain, and repeating the steps of stimulating the second region of the brain, and scanning multiple regions of the brain; and
determining the effectiveness of the drug based on a comparison of the observed neural reactions in the scan before the introduction of the drug and the observed neural reactions in the scan after the introduction of the drug.
9. The method of claim 1 , wherein said fMRI depicts a blood oxygenation level-dependent (BOLD) signal response, and wherein the method further comprises inferring a relationship between the BOLD response and the neural cell stimulation.
10. The method of claim 1 , wherein the light-responsive opsin polypeptide is a channelrhodopsin.
11. The method of claim 10 , wherein the light-responsive opsin polypeptide is a ChR2 or a VChR1 channelrhodopsin.
12. The method of claim 1 , wherein the light-responsive opsin polypeptide is an NpHR ion pump.
13. The method of claim 1 , wherein the light-responsive opsin polypeptide is encoded by a nucleotide sequence that is operably linked to a neuron-specific promoter.
14. The method of claim 13 , wherein the neuron-specific promoter is a CaMKIIα promoter.