Optogenetic Action Potential Interception via Light-Activated Protein Systems
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Solution Overview
Problem
Current optogenetic tools face limitations in effectively inhibiting and intercepting action potentials in target cells due to weak photocurrents and reduced specificity, particularly in optogenetic electrical inhibition and excitation, which affects the precision and specificity of neural modulation.
Innovation Solution
The development of systems and methods utilizing light-activated proteins, such as eArch3.0 and ASIC2a, which are delivered to target cells via nucleic acids and expression systems, allowing for optogenetic modulation of action potentials, including inhibition and interception, using light-activated proteins that facilitate ion passage across cell membranes and response proteins that enhance ion flow.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Power
If existing ion pump proteins are used for optogenetic inhibition, then temporal precision is achieved, but photocurrent strength is weak and input resistance changes are insufficient
Solution Approach 1:
The patent combines a light-activated protein (e.g., eArch3.0 proton pump) with a response protein (ASIC2a acid-sensitive ion channel) to create a two-component system. The light-activated protein generates acidification that activates the response protein, which then opens ion channels to produce strong inward currents. This merging of components resolves the contradiction by transforming weak photocurrents into strong, reliable inhibition currents while maintaining temporal precision.
2Measurement precision
If light-activated proteins are used for optogenetic excitation, then temporal precision is achieved, but specificity is reduced due to retrograde propagating action potentials
Solution Approach 1:
The patent extracts and targets action potentials at specific locations (such as axon initial segments or synapses) using spatially selective light stimulation. By applying light only to specific regions where action potentials are generated or transmitted, the system can intercept and inhibit these potentials before they propagate retrogradely to the cell body, thereby maintaining specificity while preventing harmful retrograde propagation.
3Manufacturing precision
If existing optogenetic tools are used, then cell-type resolution is maintained, but functional precision is insufficient for intercepting action potentials
Solution Approach 1:
The patent segments the optogenetic system into distinct functional components: light-activated proteins for local acidification, response proteins for ion channel activation, and delivery mechanisms for targeted expression. This segmentation allows each component to be optimized independently for its specific function while working together to achieve precise action potential interception, thereby improving functional precision without excessive overall complexity.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
These systems enable precise modulation of action potentials, improving the specificity and effectiveness of optogenetic interventions in neural applications, such as treating neurological and psychiatric conditions by effectively inhibiting and intercepting action potentials.
Implementation Method 1
light-activated proteins, such as eArch3.0 and ASIC2a, which are delivered to target cells via nucleic acids and expression systems, allowing for optogenetic modulation of action potentials
Data Source
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AI summary
Aspects of the disclosure include devices, systems and methods for optogenetic modulation of action potentials in target cells. The subject devices include light-generating devices, control devices, and delivery devices for delivering vectors to target cells. The subject systems include light-activated proteins, response proteins, nucleic acids comprising nucleotide sequences encoding these proteins, as well as expression systems that facilitate expression of these proteins in target cells. Also provided are methods of using the subject devices and systems to optogenetically inhibit and intercept action potentials in target cells, e.g., to treat a neurological or psychiatric condition in a human or non-human animal subject.