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

Abstract

Anatomic studies have demonstrated that the mesolimbic dopamine system receives a substantial afferent input from a variety of regions ranging from the prefrontal cortex through to the brain stem. However, how these afferents regulate dopamine neuron activity is still largely unknown. The mesopontine tegmentum provides a significant input to ventral tegmental area (VTA) dopamine neurons, and it has been demonstrated that discrete subdivisions within this region differentially alter dopamine neuron activity. Thus the laterodorsal tegmental nucleus provides a tonic input essential for maintaining burst firing of dopamine neurons, whereas the pedunculopontine tegmental (PPTg) nucleus regulates a transition from single-spike firing to burst firing. In contrast, the recently identified rostromedial tegmental nucleus provides an inhibitory input to the VTA and decreases spontaneous dopamine neuron activity. Here, we demonstrate that an area adjacent to the PPTg regulates both population activity as well as burst firing of VTA dopamine neurons. Specifically, N-methyl-d-aspartic acid (NMDA) activation of the lateral mesopontine tegmentum produces an increase in the number of spontaneously active dopamine neurons and an increase in the average percentage of burst firing of dopamine neurons. This increase in neuronal activity was correlated with extracellular dopamine efflux in the nucleus accumbens, as measured by in vivo microdialysis. Taken together, we provide further evidence that the mesopontine tegmentum regulates discrete dopamine neuron activity states that are relevant for the understanding of dopamine system function in both normal and disease states.