Engineered light-activated anion channel proteins and methods of use thereof

Abstract

Aspects of the disclosure include compositions, 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 light-responsive polypeptides, or nucleic acids encoding same, to target cells. The subject compositions and systems include light-activated polypeptides, nucleic acids comprising nucleotide sequences encoding these polypeptides, as well as expression systems that facilitate expression of these polypeptides in target cells. Also provided are methods of using the subject devices and systems to optogenetically manipulate action potentials in target cells, e.g., to treat a neurological or psychiatric condition in a human or animal subject.

What is claimed is: 
     
         1 . A light-activated polypeptide comprising an amino acid sequence that is at least 58% identical to SEQ ID NOS: 1, 23, 34 or 56, wherein the polypeptide functions as a light-activated anion channel. 
     
     
         2 . A nucleic acid comprising a nucleotide sequence encoding the polypeptide of  claim 1 , or a recombinant expression vector comprising a nucleic acid comprising a nucleotide sequence encoding the polypeptide of  claim 1 . 
     
     
         3 . The polypeptide according to  claim 1 , wherein the polypeptide functions as a light-activated chloride anion channel. 
     
     
         4 . The polypeptide according to  claim 1 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:1 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from T98S, E129S, E140S, E162S, V156K, H173R, T285N, V281K and/or N297Q, relative to the amino acid sequence of C1C2 (SEQ ID NO:78). 
     
     
         5 . The polypeptide according to  claim 4 , wherein the first 50 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         6 . The polypeptide according to  claim 4 , wherein the cysteine residue at position 167 is changed to a threonine, alanine or serine residue. 
     
     
         7 . The polypeptide according to  claim 4 , wherein the aspartic acid residue at position 195 is changed to an alanine residue or an asparagine residue. 
     
     
         8 . The polypeptide according to  claim 4 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 1-22. 
     
     
         9 . The polypeptide according to  claim 1 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:34 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from T98S, E129S, E140S, E162S, V156K, H173R, A285N, P281K and/or N297Q, relative to the amino acid sequence of C1V1 (SEQ ID NO:80). 
     
     
         10 . The polypeptide according to  claim 9 , wherein the first 50 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         11 . The polypeptide according to  claim 9 , wherein the cysteine residue at position 167 is changed to a threonine, alanine or serine residue. 
     
     
         12 . The polypeptide according to  claim 9 , wherein the aspartic acid residue at position 195 is changed to an alanine residue or an asparagine residue. 
     
     
         13 . The polypeptide according to  claim 9 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 34-55. 
     
     
         14 . The polypeptide according to  claim 1 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:56 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from T99S, E130S, E141S, E163S, V157K, H174R, A286N, P282K and/or N298Q, relative to the amino acid sequence of ReaChR (SEQ ID NO:81). 
     
     
         15 . The polypeptide according to  claim 14 , wherein the first 51 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         16 . The polypeptide according to  claim 14 , wherein the cysteine residue at position 168 is changed to a threonine, alanine or serine residue. 
     
     
         17 . The polypeptide according to  claim 14 , wherein the aspartic acid residue at position 196 is changed to an alanine residue or an asparagine residue. 
     
     
         18 . The polypeptide according to  claim 14 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 56-77. 
     
     
         19 . The polypeptide according to  claim 1 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:23 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from A59S, E90S, E101S, E123S, Q117K, H134R, V242K, T246N and/or N258Q, relative to the amino acid sequence of ChR2 (SEQ ID NO:79). 
     
     
         20 . The polypeptide according to  claim 19 , wherein the cysteine residue at position 128 is changed to a threonine, alanine or serine residue. 
     
     
         21 . The polypeptide according to  claim 19 , wherein the aspartic acid residue at position 156 is changed to an alanine residue or an asparagine residue. 
     
     
         22 . The polypeptide according to  claim 19 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 23-33. 
     
     
         23 . A pharmaceutical composition comprising the nucleic acid of  claim 2  and a pharmaceutically acceptable carrier. 
     
     
         24 . A cell comprising the nucleic acid of  claim 2  or the recombinant expression vector of  claim 2 . 
     
     
         25 . A system for modulating the membrane potential of a cell, the system comprising:
 a nucleic acid encoding a polypeptide that comprises an amino acid sequence that is at least 58% identical to SEQ ID NOs: 1, 23, 34 or 56, wherein the polypeptide functions as a light-activated anion channel; and   a device configured to illuminate a target location with light.   
     
     
         26 . The system according to  claim 25 , wherein the polypeptide functions as a light-activated chloride ion channel. 
     
     
         27 . The system according to  claim 25 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:1 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from T98S, E129S, E140S, E162S, V156K, H173R, T285N, V281K and/or N297Q, relative to the amino acid sequence of C1C2 (SEQ ID NO:78). 
     
     
         28 . The system according to  claim 27 , wherein the first 50 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         29 . The system according to  claim 27 , wherein the cysteine residue at position 167 is changed to a threonine, alanine or serine residue. 
     
     
         30 . The system according to  claim 27 , wherein the aspartic acid residue at position 195 is changed to an alanine residue or an asparagine residue. 
     
     
         31 . The system according to  claim 27 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 1-22. 
     
     
         32 . The system according to  claim 25 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:34 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from T98S, E129S, E140S, E162S, V156K, H173R, A285N, P281K and/or N297Q, relative to the amino acid sequence of C1V1 (SEQ ID NO:80). 
     
     
         33 . The system according to  claim 32 , wherein the first 50 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         34 . The system according to  claim 32 , wherein the cysteine residue at position 167 is changed to a threonine, alanine or serine residue. 
     
     
         35 . The system according to  claim 32 , wherein the aspartic acid residue at position 195 is changed to an alanine residue or an asparagine residue. 
     
     
         36 . The system according to  claim 32 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 34-55. 
     
     
         37 . The system according to  claim 25 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:56 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from T99S, E130S, E141S, E163S, V157K, H174R, A286N, P282K and/or N298Q, relative to the amino acid sequence of ReaChR (SEQ ID NO:81). 
     
     
         38 . The system according to  claim 37 , wherein the first 51 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         39 . The system according to  claim 37 , wherein the cysteine residue at position 168 is changed to a threonine, alanine or serine residue. 
     
     
         40 . The system according to  claim 37 , wherein the aspartic acid residue at position 196 is changed to an alanine residue or an asparagine residue. 
     
     
         41 . The system according to  claim 37 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 56-77. 
     
     
         42 . The system according to  claim 25 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:23 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from A59S, E90S, E101S, E123S, Q117K, H134R, V242K, T246N and/or N258Q, relative to the amino acid sequence of ChR2 (SEQ ID NO:79). 
     
     
         43 . The system according to  claim 42 , wherein the cysteine residue at position 128 is changed to a threonine, alanine or serine residue. 
     
     
         44 . The system according to  claim 42 , wherein the aspartic acid residue at position 156 is changed to an alanine residue or an asparagine residue. 
     
     
         45 . The system according to  claim 42 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 23-33. 
     
     
         46 . The system according to  claim 25 , wherein the device is configured to illuminate the target location with light having a wavelength ranging from about 350 to about 750 nm. 
     
     
         47 . The system according to  claim 46 , wherein the device is configured to illuminate the target location with light having a wavelength ranging from about 450 up to about 500 nm. 
     
     
         48 . The system according to  claim 25 , wherein the device is configured to constantly illuminate the target location with light. 
     
     
         49 . The system according to  claim 25 , wherein the device is configured to illuminate the target location with pulses of light. 
     
     
         50 . The system according to  claim 25 , wherein the device is configured to modulate the wavelength and/or the intensity of the light. 
     
     
         51 . The system according to  claim 49 , wherein the device is configured to modulate the frequency and/or the duration of the pulses of light. 
     
     
         52 . The system according to  claim 25 , wherein the device is configured to illuminate the target location in response to a user input. 
     
     
         53 . The system according to  52 , wherein the user input comprises: the wavelength of light, the intensity of light, the duration of a light pulse, the frequency of a light pulse, and/or the target location. 
     
     
         54 . The system according to  claim 25 , wherein the device is adapted to be implanted in a subject. 
     
     
         55 . The system according to  claim 25 , wherein the target location is: a cell, a portion of a cell, a plurality of cells, a bundle of nerve fibers, a neuromuscular junction, a central nervous system (CNS) tissue, a peripheral nervous system (PNS) tissue, or an anatomical region. 
     
     
         56 . A method for modulating the membrane potential of a cell in response to light, the method comprising:
 exposing a cell to light of an activating wavelength, wherein the cell is genetically modified with a nucleic acid encoding a polypeptide that comprises an amino acid sequence that is at least 58% identical to SEQ ID NOs: 1, 23, 34 or 56, wherein the polypeptide functions as a light-activated anion channel.   
     
     
         57 . The method according to  claim 56 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:1 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from T98S, E129S, E140S, E162S, V156K, H173R, T285N, V281K and/or N297Q, relative to the amino acid sequence of C1C2 (SEQ ID NO:78). 
     
     
         58 . The method according to  claim 57 , wherein the first 50 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         59 . The method according to  claim 57 , wherein the cysteine residue at position 167 is changed to a threonine, alanine or serine residue. 
     
     
         60 . The method according to  claim 57 , wherein the aspartic acid residue at position 195 is changed to an alanine residue or an asparagine residue. 
     
     
         61 . The method according to  claim 57 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 1-22. 
     
     
         62 . The method according to  claim 56 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:34 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from T98S, E129S, E140S, E162S, V156K, H173R, A285N, P281K and/or N297Q, relative to the amino acid sequence of C1V1 (SEQ ID NO:80). 
     
     
         63 . The method according to  claim 62 , wherein the first 50 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         64 . The method according to  claim 62 , wherein the cysteine residue at position 167 is changed to a threonine, alanine or serine residue. 
     
     
         65 . The method according to  claim 62 , wherein the aspartic acid residue at position 195 is changed to an alanine residue or an asparagine residue. 
     
     
         66 . The method according to  claim 62 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 34-55. 
     
     
         67 . The method according to  claim 56 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:56 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from T99S, E130S, E141S, E163S, V157K, H174R, A286N, P282K and/or N298Q, relative to the amino acid sequence of ReaChR (SEQ ID NO:81). 
     
     
         68 . The method according to  claim 67 , wherein the first 51 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         69 . The method according to  claim 67 , wherein the cysteine residue at position 168 is changed to a threonine, alanine or serine residue. 
     
     
         70 . The method according to  claim 67 , wherein the aspartic acid residue at position 196 is changed to an alanine residue or an asparagine residue. 
     
     
         71 . The method according to  claim 67 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 56-77. 
     
     
         72 . The method according to  claim 56 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:23 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from A59S, E90S, E101S, E123S, Q117K, H134R, V242K, T246N and/or N258Q, relative to the amino acid sequence of ChR2 (SEQ ID NO:79). 
     
     
         73 . The method according to  claim 72 , wherein the cysteine residue at position 128 is changed to a threonine, alanine or serine residue. 
     
     
         74 . The method according to  claim 72 , wherein the aspartic acid residue at position 156 is changed to an alanine residue or an asparagine residue. 
     
     
         75 . The method according to  claim 72 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 23-33. 
     
     
         76 . A method of treating a condition in a subject, the method comprising:
 genetically modifying a target cell of the subject with a nucleic acid encoding a polypeptide that comprises an amino acid sequence that is at least 58% identical to SEQ ID NOs: 1, 23, 34 or 56, wherein the polypeptide functions as a light-activated anion channel; and   exposing the target cell to light of an activating wavelength to treat the subject for the condition.   
     
     
         77 . The method according to  claim 76 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:1 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from T98S, E129S, E140S, E162S, V156K, H173R, T285N, V281K and/or N297Q, relative to the amino acid sequence of C1C2 (SEQ ID NO:78). 
     
     
         78 . The method according to  claim 77 , wherein the first 50 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         79 . The method according to  claim 77 , wherein the cysteine residue at position 167 is changed to a threonine, alanine or serine residue. 
     
     
         80 . The method according to  claim 77 , wherein the aspartic acid residue at position 195 is changed to an alanine residue or an asparagine residue. 
     
     
         81 . The method according to  claim 77 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 1-22. 
     
     
         82 . The method according to  claim 76 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:34 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from T98S, E129S, E140S, E162S, V156K, H173R, A285N, P281K and/or N297Q, relative to the amino acid sequence of C1V1 (SEQ ID NO:80). 
     
     
         83 . The method according to  claim 82 , wherein the first 50 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         84 . The method according to  claim 82 , wherein the cysteine residue at position 167 is changed to a threonine, alanine or serine residue. 
     
     
         85 . The method according to  claim 82 , wherein the aspartic acid residue at position 195 is changed to an alanine residue or an asparagine residue. 
     
     
         86 . The method according to  claim 82 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 34-55. 
     
     
         87 . The method according to  claim 76 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:56 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from T99S, E130S, E141S, E163S, V157K, H174R, A286N, P282K and/or N298Q, relative to the amino acid sequence of ReaChR (SEQ ID NO:81). 
     
     
         88 . The method according to  claim 87 , wherein the first 51 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         89 . The method according to  claim 87 , wherein the cysteine residue at position 168 is changed to a threonine, alanine or serine residue. 
     
     
         90 . The method according to  claim 87 , wherein the aspartic acid residue at position 196 is changed to an alanine residue or an asparagine residue. 
     
     
         91 . The method according to  claim 87 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 56-77. 
     
     
         92 . The method according to  claim 76 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:23 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from A59S, E90S, E101S, E123S, Q117K, H134R, V242K, T246N and/or N258Q, relative to the amino acid sequence of ChR2 (SEQ ID NO:79). 
     
     
         93 . The method according to  claim 92 , wherein the cysteine residue at position 128 is changed to a threonine, alanine or serine residue. 
     
     
         94 . The method according to  claim 92 , wherein the aspartic acid residue at position 156 is changed to an alanine residue or an asparagine residue. 
     
     
         95 . The method according to  claim 92 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 23-33. 
     
     
         96 . The method according to  claim 76 , wherein the target cell is a nerve cell. 
     
     
         97 . A method of inhibiting the formation of an action potential in a nerve cell or a portion thereof, the method comprising:
 genetically modifying the nerve cell with a nucleic acid encoding a polypeptide that comprises an amino acid sequence that is at least 58% identical to SEQ ID NOs: 1, 23, 34 or 56, wherein the polypeptide functions as a light-activated anion channel; and   exposing at least a portion of the nerve cell to light of an activating wavelength to inhibit the formation of an action potential in the nerve cell or in a portion thereof.   
     
     
         98 . The method according to  claim 97 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:1 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from T98S, E129S, E140S, E162S, V156K, H173R, T285N, V281K and/or N297Q, relative to the amino acid sequence of C1C2 (SEQ ID NO:78). 
     
     
         99 . The method according to  claim 98 , wherein the first 50 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         100 . The method according to  claim 98 , wherein the cysteine residue at position 167 is changed to a threonine, alanine or serine residue. 
     
     
         101 . The method according to  claim 98 , wherein the aspartic acid residue at position 195 is changed to an alanine residue or an asparagine residue. 
     
     
         102 . The method according to  claim 98 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 1-22. 
     
     
         103 . The method according to  claim 97 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:34 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from T98S, E129S, E140S, E162S, V156K, H173R, A285N, P281K and/or N297Q, relative to the amino acid sequence of C1V1 (SEQ ID NO:80). 
     
     
         104 . The method according to  claim 103 , wherein the first 50 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         105 . The method according to  claim 103 , wherein the cysteine residue at position 167 is changed to a threonine, alanine or serine residue. 
     
     
         106 . The method according to  claim 103 , wherein the aspartic acid residue at position 195 is changed to an alanine residue or an asparagine residue. 
     
     
         107 . The method according to  claim 103 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 34-55. 
     
     
         108 . The method according to  claim 97 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:56 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from T99S, E130S, E141S, E163S, V157K, H174R, A286N, P282K and/or N298Q, relative to the amino acid sequence of ReaChR (SEQ ID NO:81). 
     
     
         109 . The method according to  claim 108 , wherein the first 51 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         110 . The method according to  claim 108 , wherein the cysteine residue at position 168 is changed to a threonine, alanine or serine residue. 
     
     
         111 . The method according to  claim 108 , wherein the aspartic acid residue at position 196 is changed to an alanine residue or an asparagine residue. 
     
     
         112 . The method according to  claim 108 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 56-77. 
     
     
         113 . The method according to  claim 97 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:23 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from A59S, E90S, E101S, E123S, Q117K, H134R, V242K, T246N and/or N258Q, relative to the amino acid sequence of ChR2 (SEQ ID NO:79). 
     
     
         114 . The method according to  claim 113 , wherein the cysteine residue at position 128 is changed to a threonine, alanine or serine residue. 
     
     
         115 . The method according to  claim 113 , wherein the aspartic acid residue at position 156 is changed to an alanine residue or an asparagine residue. 
     
     
         116 . The method according to  claim 113 , wherein the polypeptide has an amino acid sequence as provided in any of SEQ ID NOs: 23-33. 
     
     
         117 . A kit comprising:
 a nucleic acid encoding a polypeptide that is at least 58% identical to SEQ ID NOs: 1, 23, 34 or 56, wherein the polypeptide functions as a light-activated anion channel.   
     
     
         118 . The kit according to  claim 117 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:1 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from T98S, E129S, E140S, E162S, V156K, H173R, T285N, V281K and/or N297Q, relative to the amino acid sequence of C1C2 (SEQ ID NO:78). 
     
     
         119 . The kit according to  claim 118 , wherein the first 50 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         120 . The kit according to  claim 118 , wherein the cysteine residue at position 167 is changed to a threonine, alanine or serine residue. 
     
     
         121 . The kit according to  claim 118 , wherein the aspartic acid residue at position 195 is changed to an alanine residue or an asparagine residue. 
     
     
         122 . The kit according to  claim 118 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 1-22. 
     
     
         123 . The kit according to  claim 117 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:34 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from T98S, E129S, E140S, E162S, V156K, H173R, A285N, P281K and/or N297Q, relative to the amino acid sequence of C1V1 (SEQ ID NO:80). 
     
     
         124 . The kit according to  claim 123 , wherein the first 50 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         125 . The kit according to  claim 123 , wherein the cysteine residue at position 167 is changed to a threonine, alanine or serine residue. 
     
     
         126 . The kit according to  claim 123 , wherein the aspartic acid residue at position 195 is changed to an alanine residue or an asparagine residue. 
     
     
         127 . The kit according to  claim 123 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 34-55. 
     
     
         128 . The kit according to  claim 117 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:56 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from T99S, E130S, E141S, E163S, V157K, H174R, A286N, P282K and/or N298Q, relative to the amino acid sequence of ReaChR (SEQ ID NO:81). 
     
     
         129 . The kit according to  claim 128 , wherein the first 51 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         130 . The kit according to  claim 128 , wherein the cysteine residue at position 168 is changed to a threonine, alanine or serine residue. 
     
     
         131 . The kit according to  claim 128 , wherein the aspartic acid residue at position 196 is changed to an alanine residue or an asparagine residue. 
     
     
         132 . The kit according to  claim 128 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 56-77. 
     
     
         133 . The kit according to  claim 117 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:23 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from A59S, E90S, E101S, E123S, Q117K, H134R, V242K, T246N and/or N258Q, relative to the amino acid sequence of ChR2 (SEQ ID NO:79). 
     
     
         134 . The kit according to  claim 133 , wherein the cysteine residue at position 128 is changed to a threonine, alanine or serine residue. 
     
     
         135 . The kit according to  claim 133 , wherein the aspartic acid residue at position 156 is changed to an alanine residue or an asparagine residue. 
     
     
         136 . The kit according to  claim 133 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 23-33. 
     
     
         137 . The kit according to  claim 117 , further comprising a device configured to illuminate a target location with a light. 
     
     
         138 . The kit according to  claim 137 , wherein the device is configured to illuminate the target location with light having a wavelength ranging from about 350 to about 750 nm. 
     
     
         139 . The kit according to  claim 138 , wherein the device is configured to illuminate the target location with light having a wavelength ranging from about 450 up to about 500 nm. 
     
     
         140 . The kit according to  claim 137 , wherein the device is configured to constantly illuminate the target location with a light. 
     
     
         141 . The kit according to  claim 137 , wherein the device is configured to illuminate the target location with pulses of light. 
     
     
         142 . The kit according to  claim 137 , wherein the device is configured to modulate the wavelength and/or the intensity of the light. 
     
     
         143 . The kit according to  claim 141 , wherein the device is configured to modulate the frequency and/or duration of the pulses of light. 
     
     
         144 . The kit according to  claim 137 , wherein the device is configured to illuminate the target location in response to a user input. 
     
     
         145 . The kit according to  claim 144 , wherein the user input comprises: the wavelength of light, the intensity of light, the duration of a light pulse, the frequency of a light pulse, and/or the target location to be illuminated by the light. 
     
     
         146 . The kit according to  claim 137 , wherein the device is adapted to be implanted in a subject. 
     
     
         147 . The kit according to  claim 137 , wherein the target location is: a cell, a portion of a cell, a plurality of cells, a bundle of nerve fibers, a neuromuscular junction, a central nervous system (CNS) tissue, a peripheral nervous system (PNS) tissue, or an anatomical region. 
     
     
         148 . A light-activated polypeptide comprising an amino acid sequence that is at least 60% identical to SEQ ID NOS: 94, 116, 127 or 149, wherein the polypeptide functions as a light-activated anion channel. 
     
     
         149 . A nucleic acid comprising a nucleotide sequence encoding the polypeptide of  claim 148 , or a recombinant expression vector comprising a nucleic acid comprising a nucleotide sequence encoding the polypeptide of  claim 148 . 
     
     
         150 . The polypeptide according to  claim 148 , wherein the polypeptide functions as a light-activated chloride anion channel. 
     
     
         151 . The polypeptide according to  claim 148 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:94 and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions selected from T98S, E122N, E129Q, E140S, V156R, E162S, V281R, T285N, N297Q and/or E312S, relative to the amino acid sequence of C1C2 (SEQ ID NO:78). 
     
     
         152 . The polypeptide according to  claim 151 , wherein the first 50 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         153 . The polypeptide according to  claim 151 , wherein the cysteine residue at position 167 is changed to a threonine, alanine or serine residue. 
     
     
         154 . The polypeptide according to  claim 151 , wherein the aspartic acid residue at position 195 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         155 . The polypeptide according to  claim 152 , wherein the aspartic acid residue at position 156 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         156 . The polypeptide according to  claim 151 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 94-115. 
     
     
         157 . The polypeptide according to  claim 148 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:127 and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions selected from T98S, E122N, E129Q, E140S, V156R, E162S, P281R, A285N, N297Q and/or E312S, relative to the amino acid sequence of C1V1 (SEQ ID NO:80). 
     
     
         158 . The polypeptide according to  claim 157 , wherein the first 50 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         159 . The polypeptide according to  claim 157 , wherein the cysteine residue at position 167 is changed to a threonine, alanine or serine residue. 
     
     
         160 . The polypeptide according to  claim 157 , wherein the aspartic acid residue at position 195 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         161 . The polypeptide according to  claim 158 , wherein the aspartic acid residue at position 156 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         162 . The polypeptide according to  claim 157 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 127-148. 
     
     
         163 . The polypeptide according to  claim 148 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:149 and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions selected from T99S, E123N, E130Q, E141S, V157R, E163S, P282R, A286N, N298Q and/or E313S, relative to the amino acid sequence of ReaChR (SEQ ID NO:81). 
     
     
         164 . The polypeptide according to  claim 163 , wherein the first 51 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         165 . The polypeptide according to  claim 163 , wherein the cysteine residue at position 168 is changed to a threonine, alanine or serine residue. 
     
     
         166 . The polypeptide according to  claim 163 , wherein the aspartic acid residue at position 196 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         167 . The polypeptide according to  claim 164 , wherein the aspartic acid residue at position 156 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         168 . The polypeptide according to  claim 163 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 149-170. 
     
     
         169 . The polypeptide according to  claim 148 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:116 and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions selected from A59S, E83N, E90Q, E101S, Q117R, E123S, V242R, T246N, N258Q and/or E273S, relative to the amino acid sequence of ChR2 (SEQ ID NO:79). 
     
     
         170 . The polypeptide according to  claim 169 , wherein the cysteine residue at position 128 is changed to a threonine, alanine or serine residue. 
     
     
         171 . The polypeptide according to  claim 169 , wherein the aspartic acid residue at position 156 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         172 . The polypeptide according to  claim 169 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 116-126. 
     
     
         173 . A pharmaceutical composition comprising the nucleic acid of  claim 149  and a pharmaceutically acceptable carrier. 
     
     
         174 . A cell comprising the nucleic acid of  claim 149  or the recombinant expression vector of  claim 149 . 
     
     
         175 . A system for modulating the membrane potential of a cell, the system comprising:
 a nucleic acid encoding a polypeptide that comprises an amino acid sequence that is at least 60% identical to SEQ ID NOs: 94, 116, 127 or 149, wherein the polypeptide functions as a light-activated anion channel; and   a device configured to illuminate a target location with light.   
     
     
         176 . The system according to  claim 175 , wherein the polypeptide functions as a light-activated chloride ion channel. 
     
     
         177 . The system according to  claim 175 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:94 and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions selected from T98S, E122N, E129Q, E140S, V156R, E162S, V281R, T285N, N297Q and/or E312S, relative to the amino acid sequence of C1C2 (SEQ ID NO:78). 
     
     
         178 . The system according to  claim 177 , wherein the first 50 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         179 . The system according to  claim 177 , wherein the cysteine residue at position 167 is changed to a threonine, alanine or serine residue. 
     
     
         180 . The system according to  claim 177 , wherein the aspartic acid residue at position 195 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         181 . The system according to  claim 178 , wherein the aspartic acid residue at position 156 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         182 . The system according to  claim 177 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 94-115. 
     
     
         183 . The system according to  claim 175 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:127 and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions selected from T98S, E122N, E129Q, E140S, V156R, E162S, P281R, A285N, N297Q and/or E312S, relative to the amino acid sequence of C1V1 (SEQ ID NO:80). 
     
     
         184 . The system according to  claim 183 , wherein the first 50 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         185 . The system according to  claim 183 , wherein the cysteine residue at position 167 is changed to a threonine, alanine or serine residue. 
     
     
         186 . The system according to  claim 183 , wherein the aspartic acid residue at position 195 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         187 . The system according to  claim 184 , wherein the aspartic acid residue at position 156 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         188 . The system according to  claim 183 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 127-148. 
     
     
         189 . The system according to  claim 175 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:149 and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions selected from T99S, E123N, E130Q, E141S, V157R, E163S, P282R, A286N, N298Q and/or E313S, relative to the amino acid sequence of ReaChR (SEQ ID NO:81). 
     
     
         190 . The system according to  claim 189 , wherein the first 51 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         191 . The system according to  claim 189 , wherein the cysteine residue at position 168 is changed to a threonine, alanine or serine residue. 
     
     
         192 . The system according to  claim 189 , wherein the aspartic acid residue at position 196 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         193 . The system according to  claim 190 , wherein the aspartic acid residue at position 156 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         194 . The system according to  claim 189 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 149-170. 
     
     
         195 . The system according to  claim 175 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:116 and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions selected from A59S, E83N, E90Q, E101S, Q117R, E123S, V242R, T246N, N258Q and/or E273S, relative to the amino acid sequence of ChR2 (SEQ ID NO:79). 
     
     
         196 . The system according to  claim 195 , wherein the cysteine residue at position 128 is changed to a threonine, alanine or serine residue. 
     
     
         197 . The system according to  claim 195 , wherein the aspartic acid residue at position 156 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         198 . The system according to  claim 195 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 116-126. 
     
     
         199 . The system according to  claim 175 , wherein the device is configured to illuminate the target location with light having a wavelength ranging from about 350 to about 750 nm. 
     
     
         200 . The system according to  claim 199 , wherein the device is configured to illuminate the target location with light having a wavelength ranging from about 450 up to about 500 nm. 
     
     
         201 . The system according to  claim 175 , wherein the device is configured to constantly illuminate the target location with light. 
     
     
         202 . The system according to  claim 175 , wherein the device is configured to illuminate the target location with pulses of light. 
     
     
         203 . The system according to  claim 175 , wherein the device is configured to modulate the wavelength and/or the intensity of the light. 
     
     
         204 . The system according to  claim 202 , wherein the device is configured to modulate the frequency and/or the duration of the pulses of light. 
     
     
         205 . The system according to  claim 175 , wherein the device is configured to illuminate the target location in response to a user input. 
     
     
         206 . The system according to  claim 205 , wherein the user input comprises: the wavelength of light, the intensity of light, the duration of a light pulse, the frequency of a light pulse, and/or the target location. 
     
     
         207 . The system according to  claim 175 , wherein the device is adapted to be implanted in a subject. 
     
     
         208 . The system according to  claim 175 , wherein the target location is: a cell, a portion of a cell, a plurality of cells, a bundle of nerve fibers, a neuromuscular junction, a central nervous system (CNS) tissue, a peripheral nervous system (PNS) tissue, or an anatomical region. 
     
     
         209 . A method for modulating the membrane potential of a cell in response to light, the method comprising:
 exposing a cell to light of an activating wavelength, wherein the cell is genetically modified with a nucleic acid encoding a polypeptide that comprises an amino acid sequence that is at least 58% identical to SEQ ID NOs: 94, 116, 127 or 149, wherein the polypeptide functions as a light-activated anion channel.   
     
     
         210 . The method according to  claim 209 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:94 and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions selected from T98S, E122N, E129Q, E140S, V156R, E162S, V281R, T285N, N297Q and/or E312S, relative to the amino acid sequence of C1C2 (SEQ ID NO:78). 
     
     
         211 . The method according to  claim 210 , wherein the first 50 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         212 . The method according to  claim 210 , wherein the cysteine residue at position 167 is changed to a threonine, alanine or serine residue. 
     
     
         213 . The method according to  claim 210 , wherein the aspartic acid residue at position 195 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         214 . The method according to  claim 211 , wherein the aspartic acid residue at position 156 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         215 . The method according to  claim 210 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 94-115. 
     
     
         216 . The method according to  claim 209 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:127 and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions selected from T98S, E122N, E129Q, E140S, V156R, E162S, P281R, A285N, N297Q and/or E312S, relative to the amino acid sequence of C1V1 (SEQ ID NO:80). 
     
     
         217 . The method according to  claim 216 , wherein the first 50 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         218 . The method according to  claim 216 , wherein the cysteine residue at position 167 is changed to a threonine, alanine or serine residue. 
     
     
         219 . The method according to  claim 216 , wherein the aspartic acid residue at position 195 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         220 . The method according to  claim 217 , wherein the aspartic acid residue at position 156 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         221 . The method according to  claim 216 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 127-148. 
     
     
         222 . The method according to  claim 210 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:149 and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions selected from T99S, E123N, E130Q, E141S, V157R, E163S, P282R, A286N, N298Q and/or E313S, relative to the amino acid sequence of ReaChR (SEQ ID NO:81). 
     
     
         223 . The method according to  claim 222 , wherein the first 51 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         224 . The method according to  claim 222 , wherein the cysteine residue at position 168 is changed to a threonine, alanine or serine residue. 
     
     
         225 . The method according to  claim 222 , wherein the aspartic acid residue at position 196 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         226 . The method according to  claim 223 , wherein the aspartic acid residue at position 156 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         227 . The method according to  claim 222 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 149-170. 
     
     
         228 . The method according to  claim 209 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:116 and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions selected from A59S, E83N, E90Q, E101S, Q117R, E123S, V242R, T246N, N258Q and/or E273S, relative to the amino acid sequence of ChR2 (SEQ ID NO:79). 
     
     
         229 . The method according to  claim 228 , wherein the cysteine residue at position 128 is changed to a threonine, alanine or serine residue. 
     
     
         230 . The method according to  claim 228 , wherein the aspartic acid residue at position 156 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         231 . The method according to  claim 228 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 116-126. 
     
     
         232 . A method of treating a condition in a subject, the method comprising:
 genetically modifying a target cell of the subject with a nucleic acid encoding a polypeptide that comprises an amino acid sequence that is at least 60% identical to SEQ ID NOs: 94, 116, 127 or 149, wherein the polypeptide functions as a light-activated anion channel; and   exposing the target cell to light of an activating wavelength to treat the subject for the condition.   
     
     
         233 . The method according to  claim 232 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:94 and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions selected from T98S, E122N, E129Q, E140S, V156R, E162S, V281R, T285N, N297Q and/or E312S, relative to the amino acid sequence of C1C2 (SEQ ID NO:78). 
     
     
         234 . The method according to  claim 233 , wherein the first 50 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         235 . The method according to  claim 233 , wherein the cysteine residue at position 167 is changed to a threonine, alanine or serine residue. 
     
     
         236 . The method according to  claim 233 , wherein the aspartic acid residue at position 195 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         237 . The method according to  claim 234 , wherein the aspartic acid residue at position 156 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         238 . The method according to  claim 233 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 94-115. 
     
     
         239 . The method according to  claim 232 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:127 and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions selected from T98S, E122N, E129Q, E140S, V156R, E162S, P281R, A285N, N297Q and/or E312S, relative to the amino acid sequence of C1V1 (SEQ ID NO:80). 
     
     
         240 . The method according to  claim 239 , wherein the first 50 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         241 . The method according to  claim 239 , wherein the cysteine residue at position 167 is changed to a threonine, alanine or serine residue. 
     
     
         242 . The method according to  claim 239 , wherein the aspartic acid residue at position 195 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         243 . The method according to  claim 240 , wherein the aspartic acid residue at position 156 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         244 . The method according to  claim 239 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 127-148. 
     
     
         245 . The method according to  claim 232 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:149 and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions selected from T99S, E123N, E130Q, E141S, V157R, E163S, P282R, A286N, N298Q and/or E313S, relative to the amino acid sequence of ReaChR (SEQ ID NO:81). 
     
     
         246 . The method according to  claim 245 , wherein the first 51 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         247 . The method according to  claim 245 , wherein the cysteine residue at position 168 is changed to a threonine, alanine or serine residue. 
     
     
         248 . The method according to  claim 245 , wherein the aspartic acid residue at position 196 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         249 . The method according to  claim 246 , wherein the aspartic acid residue at position 156 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         250 . The method according to  claim 245 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 149-170. 
     
     
         251 . The method according to  claim 232 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:116 and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions selected from A59S, E83N, E90Q, E101S, Q117R, E123S, V242R, T246N, N258Q and/or E273S, relative to the amino acid sequence of ChR2 (SEQ ID NO:79). 
     
     
         252 . The method according to  claim 251 , wherein the cysteine residue at position 128 is changed to a threonine, alanine or serine residue. 
     
     
         253 . The method according to  claim 251 , wherein the aspartic acid residue at position 156 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         254 . The method according to  claim 251 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 116-126. 
     
     
         255 . The method according to  claim 232 , wherein the target cell is a nerve cell. 
     
     
         256 . A method of inhibiting the formation of an action potential in a nerve cell or a portion thereof, the method comprising:
 genetically modifying the nerve cell with a nucleic acid encoding a polypeptide that comprises an amino acid sequence that is at least 60% identical to SEQ ID NOs: 94, 116, 127 or 149, wherein the polypeptide functions as a light-activated anion channel; and   exposing at least a portion of the nerve cell to light of an activating wavelength to inhibit the formation of an action potential in the nerve cell or in a portion thereof.   
     
     
         257 . The method according to  claim 256 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:94 and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions selected from T98S, E122N, E129Q, E140S, V156R, E162S, V281R, T285N, N297Q and/or E312S, relative to the amino acid sequence of C1C2 (SEQ ID NO:78). 
     
     
         258 . The method according to  claim 257 , wherein the first 50 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         259 . The method according to  claim 257 , wherein the cysteine residue at position 167 is changed to a threonine, alanine or serine residue. 
     
     
         260 . The method according to  claim 257 , wherein the aspartic acid residue at position 195 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         261 . The method according to  claim 258 , wherein the aspartic acid residue at position 156 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         262 . The method according to  claim 257 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 94-115. 
     
     
         263 . The method according to  claim 256 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:127 and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions selected from T98S, E122N, E129Q, E140S, V156R, E162S, P281R, A285N, N297Q and/or E312S, relative to the amino acid sequence of C1V1 (SEQ ID NO:80). 
     
     
         264 . The method according to  claim 263 , wherein the first 50 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         265 . The method according to  claim 263 , wherein the cysteine residue at position 167 is changed to a threonine, alanine or serine residue. 
     
     
         266 . The method according to  claim 263 , wherein the aspartic acid residue at position 195 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         267 . The method according to  claim 264 , wherein the aspartic acid residue at position 156 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         268 . The method according to  claim 263 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 127-148. 
     
     
         269 . The method according to  claim 256 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:149 and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions selected from T99S, E123N, E130Q, E141S, V157R, E163S, P282R, A286N, N298Q and/or E313S, relative to the amino acid sequence of ReaChR (SEQ ID NO:81). 
     
     
         270 . The method according to  claim 269 , wherein the first 51 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         271 . The method according to  claim 269 , wherein the cysteine residue at position 168 is changed to a threonine, alanine or serine residue. 
     
     
         272 . The method according to  claim 269 , wherein the aspartic acid residue at position 196 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         273 . The method according to  claim 270 , wherein the aspartic acid residue at position 156 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         274 . The method according to  claim 269 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 149-170. 
     
     
         275 . The method according to  claim 256 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:116 and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions selected from A59S, E83N, E90Q, E101S, Q117R, E123S, V242R, T246N, N258Q and/or E273S, relative to the amino acid sequence of ChR2 (SEQ ID NO:79). 
     
     
         276 . The method according to  claim 275 , wherein the cysteine residue at position 128 is changed to a threonine, alanine or serine residue. 
     
     
         277 . The method according to  claim 275 , wherein the aspartic acid residue at position 156 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         278 . The method according to  claim 275 , wherein the polypeptide has an amino acid sequence as provided in any of SEQ ID NOs: 116-126. 
     
     
         279 . A kit comprising:
 a nucleic acid encoding a polypeptide that is at least 60% identical to SEQ ID NOs: 94, 116, 127 or 149, wherein the polypeptide functions as a light-activated anion channel.   
     
     
         280 . The kit according to  claim 279 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:94 and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions selected from T98S, E122N, E129Q, E140S, V156R, E162S, V281R, T285N, N297Q and/or E312S, relative to the amino acid sequence of C1C2 (SEQ ID NO:78). 
     
     
         281 . The kit according to  claim 280 , wherein the first 50 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         282 . The kit according to  claim 280 , wherein the cysteine residue at position 167 is changed to a threonine, alanine or serine residue. 
     
     
         283 . The kit according to  claim 280 , wherein the aspartic acid residue at position 195 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         284 . The kit according to  claim 281 , wherein the aspartic acid residue at position 156 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         285 . The kit according to  claim 280 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 94-115. 
     
     
         286 . The kit according to  claim 279 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:127 and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions selected from T98S, E122N, E129Q, E140S, V156R, E162S, P281R, A285N, N297Q and/or E312S, relative to the amino acid sequence of C1V1 (SEQ ID NO:80). 
     
     
         287 . The kit according to  claim 286 , wherein the first 50 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         288 . The kit according to  claim 286 , wherein the cysteine residue at position 167 is changed to a threonine, alanine or serine residue. 
     
     
         289 . The kit according to  claim 286 , wherein the aspartic acid residue at position 195 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         290 . The kit according to  claim 287 , wherein the aspartic acid residue at position 156 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         291 . The kit according to  claim 286 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 127-148. 
     
     
         292 . The kit according to  claim 279 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:149 and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions selected from T99S, E123N, E130Q, E141S, V157R, E163S, P282R, A286N, N298Q and/or E313S, relative to the amino acid sequence of ReaChR (SEQ ID NO:81). 
     
     
         293 . The kit according to  claim 292 , wherein the first 51 N-terminal amino acid residues are replaced by the following amino acids residues: MDYGGALSAVG (SEQ ID NO:82). 
     
     
         294 . The kit according to  claim 292 , wherein the cysteine residue at position 168 is changed to a threonine, alanine or serine residue. 
     
     
         295 . The kit according to  claim 292 , wherein the aspartic acid residue at position 196 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         296 . The kit according to  claim 293 , wherein the aspartic acid residue at position 156 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         297 . The kit according to  claim 292 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 149-170. 
     
     
         298 . The kit according to  claim 279 , wherein the polypeptide has an amino acid sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or is 100% identical to the amino acid sequence provided in SEQ ID NO:116 and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions selected from A59S, E83N, E90Q, E101S, Q117R, E123S, V242R, T246N, N258Q and/or E273S, relative to the amino acid sequence of ChR2 (SEQ ID NO:79). 
     
     
         299 . The kit according to  claim 298 , wherein the cysteine residue at position 128 is changed to a threonine, alanine or serine residue. 
     
     
         300 . The kit according to  claim 298 , wherein the aspartic acid residue at position 156 is changed to an alanine residue, an asparagine residue, or a cysteine residue. 
     
     
         301 . The kit according to  claim 298 , wherein the polypeptide has an amino acid sequence as provided in any one of SEQ ID NOs: 116-126. 
     
     
         302 . The kit according to  claim 279 , further comprising a device configured to illuminate a target location with a light. 
     
     
         303 . The kit according to  claim 302 , wherein the device is configured to illuminate the target location with light having a wavelength ranging from about 350 to about 750 nm. 
     
     
         304 . The kit according to  claim 303 , wherein the device is configured to illuminate the target location with light having a wavelength ranging from about 450 up to about 500 nm. 
     
     
         305 . The kit according to  claim 302 , wherein the device is configured to constantly illuminate the target location with a light. 
     
     
         306 . The kit according to  claim 302 , wherein the device is configured to illuminate the target location with pulses of light. 
     
     
         307 . The kit according to  claim 302 , wherein the device is configured to modulate the wavelength and/or the intensity of the light. 
     
     
         308 . The kit according to  claim 302 , wherein the device is configured to modulate the frequency and/or duration of the pulses of light. 
     
     
         309 . The kit according to  claim 302 , wherein the device is configured to illuminate the target location in response to a user input. 
     
     
         310 . The kit according to  claim 309 , wherein the user input comprises: the wavelength of light, the intensity of light, the duration of a light pulse, the frequency of a light pulse, and/or the target location to be illuminated by the light. 
     
     
         311 . The kit according to  claim 302 , wherein the device is adapted to be implanted in a subject. 
     
     
         312 . The kit according to  claim 302 , wherein the target location is: a cell, a portion of a cell, a plurality of cells, a bundle of nerve fibers, a neuromuscular junction, a central nervous system (CNS) tissue, a peripheral nervous system (PNS) tissue, or an anatomical region.