Controlling Neuronal Activity

Abstract

With a new technology called optogenetics, it is possible to turn neuronal activity on and off in distinct neuronal populations, using cell-type specific, optically-sensitive, molecular, neuronal activity "switches." These "switches" are microbial, light-sensitive ion conductance-regulating proteins, exemplified by channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR). They are individually introduced into neuronal populations in the brain and become part of the cellular machinery. Ion flux-regulating activity of these “switches” can be controlled externally with light pulses. ChR2 is a cation channel that allows sodium ions to pass into a neuron after it has been activated by approximately 470 nm blue light (thereby increasing activity of the neuron and increasing action potentials). NpHR is a chloride pump that transfers chloride anions into the neuron after it has been activated by approximately 580 nm yellow light (thereby increasing accumulation of negative charge inside the cell and suppressing activity of the neuron). For application of this technology, light of the proper wavelength is delivered to the brain region of interest using a fiberoptic-based system or a light-emitting diode (LED). ChR2 and NpHR can be controlled independently to either increase action-potential firing of specific target neurons or to suppress neural activity, respectively, in intact tissue. In animal experiments, the LED or fiberoptic can be tethered to an external power source with lightweight flexible connectors, allowing stimulation during normal, freely moving behavior. The genes encoding these proteins are introduced into the brain with viral vectors and are expressed in distinct populations of neurons in vivo using specific DNA promoters fused to the gene, thereby guiding expression only in the cell type of choice.