Mice detect and discriminate temporal patterns of mesoscale optogenetic cortical stimulation

Researchers have discovered that mice can detect and differentiate the subtle timing patterns of cortical optogenetic stimulation. This finding challenges the notion that animals only react to external stimuli and could potentially perceive the neural stimulation itself, a phenomenon called optoception. To test this hypothesis, a team of scientists utilized a mesoscale cortical photostimulation technique involving a small, blue LED implanted over the auditory cortex of four mice genetically engineered to produce Channelrhodopsin-2 (ChR2) in excitatory neurons. These mice learned a task in which 20 Hz cortical photostimulation served as the target.

In the trials, the ChR2-positive mice were able to distinguish the cortical photostimulation from both an external LED of matching wavelength and pulse rate, as well as from an acoustic noise that matched in amplitude-modulation rate. Additionally, the mice could differentiate between 20- and 10-Hz cortical photostimulation. Interestingly, when the optical power of the implanted LED was reduced, the mice's ability to discriminate between rates initially decreased, but then improved across training sessions, indicating perceptual learning.

To further validate the phenomenon, the researchers tested two additional mice with 11 randomly interleaved rates ranging from 10-20 Hz. The lick probability of these mice followed a saturating rate-dependent function, suggesting that the mice's response was contingent on the stimulation rate. In contrast, two ChR2-negative littermates failed to acquire the photostimulation-locked behavioral responding, further supporting the idea that optoception is dependent on the presence of ChR2-positive neurons.

In conclusion, the researchers' study demonstrates that mesoscale cortical optogenetic stimulation generates a graded and learnable artificial percept whose behavioral readout depends on the stimulation rate and optical power. This single-LED preparation offers a cost-effective and wavelength-extensible platform for psychometric analysis of optoception, opening new avenues for studying the subtle effects of neural stimulation on animal behavior.