Prefrontal cortical up states are synchronized with ventral tegmental area activity

The innervation of the prefrontal cortex (PFC) by the ventral tegmental area (VTA) has an important role in incentive-motivation and cognitive functions. Although this projection has been extensively studied, the precise actions of its transmitters, dopamine (DA) and GABA, on PFC pyramidal neurons remain to be determined. We have recently shown that VTA stimulation elicits a sustained depolarization in PFC pyramidal neurons resembling the periodic depolarizations (up states) these neurons exhibit. This response was shortened by a D-1 antagonist, suggesting that DA may sustain depolarized up states in PFC neurons. Here, we tested whether spontaneous PFC up states in vivo require spontaneous VTA activity. Intracellular recordings from PFC neurons conducted simultaneously with VTA local field potentials (LFPs) revealed PFC membrane potential fluctuations occurring synchronously with VTA field potential transitions. Extracellular PFC recordings performed simultaneously with VTA LFPs also indicated a high coherence between these two regions, with VTA oscillations trailing PFC oscillations by a few milliseconds. Furthermore, blockade of VTA activity with lidocaine transiently eliminated PFC LFPs, but not PFC cell up states; instead, up states became irregular during intra-VTA lidocaine administration. These results suggest that baseline levels of VTA activity are necessary for synchronizing PFC pyramidal neurons in the up-down oscillations observed in the anesthetized preparation, allowing the emergence of slow EEG components. (C) 2004 Wiley-Liss, Inc.