Cellular mechanisms of brain state-€“dependent gain modulation in visual cortex

6 years ago



This paper investigates the mechanism of enhanced cortical firing rates during locomotion, a phenomenon reported elsewhere that has yet to be characterized well. The authors first performed whole-cell recordings in V1 L2/3 cells in mice running on a treadmill, and found that locomotion was associated with tonic depolarization as well as more robust evoked spiking responses. These effects could either be due to (1) reduced inhibition, (2) increased feedforward excitation, or (3) neuromodulation. They rule out the first possibility by recording intracellularly from PV+ and SOM+ cells and showing that their firing rates also increase during locomotion. The second possibility is ruled out by recording from L4 cells, which do not show a spontaneous rate increase during running. The addition of cholinergic antagonists causes the cortex to spontaneously alternate between UP and DOWN states, but does not abolish locomotion-induced depolarization. Noradrenergic antagonists, on the other hand, do block the effects of locomotion, indicating that NE is most likely the mediator of running-related changes in visual cortex. Even after a glutamatergic blockade (CNQX + AP5), locomotion-induced depolarization remains, although it is attenuated relative to the baseline state.