The ventral tegmental area modulates intracortical microstimulation (ICMS)-evoked M1 activity in a time-dependent manner

Intracortical microstimulation (ICMS)-evoked neural activity combined with ventral tegmental area (VTA) stimulation was studied in rat primary motor cortex (M1). We used voltage-sensitive dye (VSD) imaging to analyze the spatiotemporal dynamics of M1 activity following VTA-M1 paired stimulation. VTA stimulation was preceded by M1 ICMS at inter-stimulus intervals (ISIs) of 15-350 ms. VSD imaging showed an excitatory-inhibitory sequence of neural activity after composing VTA stimulus- and ICMS-induced M1 neural activity. To evaluate the net ICMS M1 response, the optical response to unpaired VTA stimulation was subtracted from the VTA-M1 paired response. This revealed that the net ICMS-evoked M1 neural activity was inhibited when the ISI was 30-50 ms, but highly facilitated when the ISI was 100-350 ms. These results suggest that VTA modulates M1 excitability in the order of tens to hundreds of milliseconds and might directly affect the motor command generation process in the M1.