Exploring the neuronal basis of brain states

© 2014 EPFL

© 2014 EPFL

Colleagues researchers at the EPFL Brain Mind Institute have determined that acetylcholine in the cortex plays an important role in controlling brain states.

“Brain state” is a term that describes the dynamic electrical pattern of activity in our brain during different behavioral activities, like thinking, sleeping, learning etc. Although critical for understanding behavior and even mental disorders, the cellular basis of brain states has been difficult to investigate. Professor Carl Petersen, senior scientist Sylvain Crochain, at the Laboratory of Sensory Processing (BMI) have now discovered a neurochemical pathway that contributes to controlling brain states in mice. Their work is published in Cell Reports.

Carl Petersen and Sylvain Crochet have found that brain states in mice are regulated by signals from cholinergic neurons that act on the somatosensory center in the mouse neocortex, called the “barrel cortex”. The scientists examined whisking in mice as a test activity, which their previous work has already shown to be associated with an important change in the cortical state, driven in part by increased thalamic activity. Their new work points to a role of acetylcholine as a second key signal in determining brain states.

To uncover this cholinergic signal, the researchers used mice whose cholinergic neurons had been genetically modified to express the light-gated cation channel encoded by channelrhodopsin-2. This approach, called optogenetics, allows genetically-defined populations of neurons to be turned on by stimulating them with light. In addition to optogenetics, the researchers also used whole-cell recordings, pharmacological stimulation, and axonal-calcium imaging to determine the contribution of cholinergic signals to the whisking brain state.

As the mice moved their whiskers back and forth rapidly (frequency of about 8–12 Hz), the movement was recorded with a high-speed camera. The images were fed into a computer, which measured the angle of whisker movement and matched it to signals from neurons in the barrel cortex. The data showed a prominent cholinergic signal in the barrel cortex during whisking, which causes a suppression of slow cortical activity. This new study sheds light upon the specific role of acetylcholine in maintaining high vigilance states.

Eggermann E, Kremer Y, Crochet S, Petersen CCH. Cholinergic Signals in Mouse Barrel Cortex during Active Whisker Sensing. Cell Reports (2014), http://dx.doi.org/10.1016/j.celrep.2014.11.005