Medial prefrontal cortical output neurons to the ventral tegmental area (VTA) and their responses to burst-patterned stimulation of the VTA: neuroanatomical and in vivo electrophysiological analyses.

Abstract

During a delayed period in a delayed-response task, prefrontal cortical neurons show a change in neuronal firing rate that is dependent on a functional mesocortical dopamine input. This change in firing rate has been attributed to be part of the cellular processes underlying working memory. However, it is unclear what neural mechanisms activate mesocortical dopamine neurons to provide an optimal level of dopamine to modulate the firing of the medial prefrontal cortical (mPFC) neurons. This study examined the possibility of whether mPFC neurons that project to the ventral tegmental area (VTA) might activate the ascending mesocortical dopamine neurons. To determine the locations of the mPFC-->VTA neurons, cholera toxin subunit B was microinjected into the VTA. Retrogradely labeled mPFC neurons mainly reside in the deep lamina V and VI. In vivo single unit recording in urethane-anesthetized rats were also used to determine the responses of some of these neurons to burst-patterned stimulation of the VTA. Single-pulse stimulation (1 Hz) of the VTA antidromically activated burst firing mPFC-->VTA neurons. In response to burst-patterned stimulation of the VTA, which mimicked burst firing of VTA dopamine neurons (4-10 pulses at 10-15 Hz cycled at 0.5-3 Hz), the temporal structure of spontaneous burst firing patterns of these neurons but not their mean firing rate were changed. However, the mean firing rate of the non-VTA projecting neurons (i.e., no antidromic response to VTA stimulations) was either increased or decreased by similar burst-patterned stimulation of the VTA. These data suggest that burst-patterned stimulation of the ascending VTA-->mPFC or putative mesocortical dopamine neurons might have released dopamine and/or other neuromodulators to modulate the temporal code, rather than the rate code, of mPFC-->VTA neurons. Medial PFC neurons that project elsewhere (e.g., nucleus accumbens or mediodorsal thalamus) may mediate the sustained firing rate changes during, e.g., short-term working memory.