Informational lesions: optical perturbation of spike timing and neural synchrony via microbial opsin gene fusions

Front Mol Neurosci. 2009 Aug 27:2:12. doi: 10.3389/neuro.02.012.2009. eCollection 2009.


Synchronous neural activity occurs throughout the brain in association with normal and pathological brain functions. Despite theoretical work exploring how such neural coordination might facilitate neural computation and be corrupted in disease states, it has proven difficult to test experimentally the causal role of synchrony in such phenomena. Attempts to manipulate neural synchrony often alter other features of neural activity such as firing rate. Here we evaluate a single gene which encodes for the blue-light gated cation channel channelrhodopsin-2 and the yellow-light driven chloride pump halorhodopsin from Natronobacterium pharaonis, linked by a 'self-cleaving' 2A peptide. This fusion enables proportional expression of both opsins, sensitizing neurons to being bi-directionally controlled with blue and yellow light, facilitating proportional optical spike insertion and deletion upon delivery of trains of precisely-timed blue and yellow light pulses. Such approaches may enable more detailed explorations of the causal role of specific features of the neural code.

Keywords: channelrhodopsin-2; fusion protein; halorhodopsin; optogenetics; synchrony.