Where Anxiety Resides in the Brain

Optogenetics is a technology that allows targeted, fast control of precisely defined events in biological systems. By delivering optical control at the speed (millisecond-scale) and with the precision (cell type–specific) required for biological processing, optogenetic approaches have opened new landscapes for the study of biology, both in health and disease.

Opsins are light sensitive membrane-bound receptors that convert a photon of light into an electrochemical signal.  Karl Deisseroth at Stanford University wanted to learn if light sensitive molecules such as opsins could be incorporated into pockets of brain cells to selectively activate or inhibit them.  Channelrhodopsin-2 (ChR2) is a gated light-sensitive cation channel (an opsin), isolated from algae, that uses a molecule of all-trans retinal to absorb photons.  A key advantage of microbial opsins (including ChR2, VChR1, NpHR, and Arch) is that they are fully functional in the mammalian brain without the addition of exogenous co-factors and respond to visible-spectrum light. 

Karl Deisseroth Speaking at SFN 2009 from Deisseroth Lab on Vimeo.

The next step was to integrate ChR2 into specific cell types in order to probe their response to light excitation.  Deisseroth and colleagues Ed Boyden and Feng Zhang used genetically modified viruses to deliver the ChR2 genes to very specific clusters of brain cells.  When Deisseroth et al. expressed ChR2 in hippocampal neurons in the mouse brain, they found the cells with ChR2 responded to the light stimulation, opening the channel and initiating the flow of ions, which resulted in an action potential in those neurons.  The far-fetched research concept worked, allowing Deisseroth and colleagues to turn on and off selective groups of brain cells enabling the precise study of brain function for the first time.

Scientists have long been hobbled by the lack of a good technology to explore how clusters of neurons coordinate their activity, the Deisseroth research could change that paradigm.  Prior research suggests the amygdala plays a role in anxiety.  Using optogenetic manipulation of various amygdala pathways, Deisseroth and colleagues examined how mouse behavior was affected. Since mice display anxiety-related behaviors in open spaces, they measured changes in anxiety by analyzing how much time mice spent exploring the center of an open field, or exploring the length of a platform without walls.  Confirming the presence of cells that modulate anxiety levels of mice in the amygdala is the first step in finding new drugs that are more efficient at targeting cells to dampen the symptoms of anxiety. 

How cool is this technology?!?