The lateral mesopontine tegmentum regulates both tonic and phasic activity 1 of VTA dopamine neurons

20 Anatomical studies have demonstrated that the mesolimbic dopamine system receives a 21 substantial afferent input from a variety of regions ranging from the prefrontal cortex 22 through to the brainstem. However, how these afferents regulate dopamine neuron activity 23 is still largely unknown. The mesopontine tegmentum provides a significant input to ventral 24 tegmental area (VTA) dopamine neurons and it has been demonstrated that discrete 25 subdivisions within this region differentially alter dopamine neuron activity. Thus, the 26 laterodorsal tegmental nucleus provides a tonic input essential for maintaining burst firing of 27 dopamine neurons, while the pedunculopontine tegmental (PPTg) nucleus regulates a 28 transition from single-spike firing to burst firing. In contrast, the recently identified 29 rostromedial tegmental nucleus provides an inhibitory input to the VTA and decreases 30 spontaneous dopamine neuron activity. Here we demonstrate that an area adjacent to the 31 PPTg regulates both population activity as well as burst firing of VTA dopamine neurons. 32 Specifically, NMDA activation of the lateral mesopontine tegmentum produces an increase in 33 the number of spontaneously active dopamine neurons and an increase in the average 34 percent burst firing of dopamine neurons. This increase in neuronal activity was correlated 35 with extracellular dopamine efflux in the nucleus accumbens, as measured by in vivo 36 microdialysis. Taken together we provide further evidence that the mesopontine tegmentum 37 regulates discrete dopamine neuron activity states that are relevant for the understanding of 38 dopamine system function in both normal and disease states.