Optical tissue interface method and apparatus for stimulating cells

Abstract

In one example, a system electrically stimulates target cells of a living animal using an elongated structure, a modulation circuit and a light pathway such as provided by an optical fiber arrangement. The elongated structure is for insertion into a narrow passageway in the animal such that an end of the elongated structure is sufficiently near the target cells to deliver stimulation thereto. The modulation circuit is for modulating the target cells while the elongated structure is in the narrow passageway, where the modulation circuit is adapted to deliver viral vectors through the elongated structure for expressing light responsive proteins in the target cells. The light pathway is used for stimulating the target cells by delivering light to the light-responsive proteins in the target cells.

1 .- 17 . (canceled) 
     
     
         18 . A method for electrically stimulating a target cell of a living animal in vivo, the method comprising:
 delivering a viral vector to a target cell, wherein the viral vector comprises a nucleotide sequence encoding a light-activatable polypeptide having at least 75% amino acid sequence identity to the ChR2 amino acid sequence set forth in SEQ ID NO:1, wherein the nucleotide sequence is operably linked to a target cell type-specific promoter, and wherein said delivering provides for expression of the light-activatable polypeptide selectively in the target cell;   inserting an optical fiber into a narrow passageway in the animal such that an end of the optical fiber is sufficiently near the target cell to deliver stimulation thereto, and   stimulating the target cell by using the optical fiber to deliver light to the light-activatable polypeptide expressed in the target cell.   
     
     
         19 . The method of  claim 18 , wherein the target cell is an excitable cell. 
     
     
         20 . The method of  claim 18 , wherein the target cell is a nerve cell, a heart cell, or a muscle cell. 
     
     
         21 . The method of  claim 18 , further comprising the step of measuring electrical properties of the target cell using a microelectrode. 
     
     
         22 . The method of  claim 18 , wherein the target cell is an electrically active cell of a sinoatrial node and wherein the stimulating the target cell causes pacing of a heart. 
     
     
         23 . The method of  claim 18 , wherein the promoter is a CaMKIIα promoter. 
     
     
         24 . The method of  claim 18 , wherein the nucleotide sequence is optimized for expression in mammalian cells. 
     
     
         25 . The method of  claim 18 , wherein the light-activatable polypeptide has at least 85% amino acid sequence identity to amino acid sequence set forth in SEQ ID NO:1. 
     
     
         26 . The method of  claim 18 , wherein the light-activatable polypeptide has at least 95% amino acid sequence identity to amino acid sequence set forth in SEQ ID NO:1. 
     
     
         27 . The method of  claim 18 , wherein the target cell is in the anterior cingulate, the prefrontal cortex, the posterior cingulate gyrus, or a Brodmann Area. 
     
     
         28 . The method of  claim 18 , wherein the animal is a mammal. 
     
     
         29 . The method of  claim 18 , wherein the viral vector is a lentiviral vector, an adeno-associated viral vector, a retroviral vector, or an adenoviral vector. 
     
     
         30 . The method of  claim 29 , wherein the viral vector is an adeno-associated viral vector or a lentiviral vector.