Integrity of the mesocortical dopaminergic system is necessary for complete expression of in vivo hippocampal-prefrontal cortex long-term potentiation

The prefrontal cortex receives dopaminergic inputs from the ventral tegment al area and excitatory inputs from the hippocampus. Both afferent pathways target in close proximity dendritic spines of pyramidal cells in layer V-VI of the prefrontal cortex. In view of the prominent role of dopamine in cog nitive functions we examined the effects of ventral tegmental area stimulat ion on the induction of long-term potentiation in the hippocampal-prefronta l cortex pathway of anesthetized rats. Stimulation of the ventral tegmental area at a frequency known to evoke dopamine overflow in the prefrontal cor tex produces a long-lasting enhancement of the magnitude of the hippocampal -prefrontal cortex long-term potentiation. The role of dopamine was further examined by investigating the effects of prefrontocortical dopamine deplet ion induced by an electrolytic ventral tegmental area lesion. A significant correlation (r = 0.8; P < 0.001; n = 14) was obtained between cortical dop amine levels and cortical long-term potentiation amplitude, a depletion of more than 50% of cortical levels corresponding to a dramatic decrease in hi ppocampal-prefrontal cortex long-term potentiation. However, a recovery to normal long-term potentiation was observed Ih after tetanic stimulation. In contrast to the effects on long-term potentiation, ventral tegmental area stimulation, when applied at low or high frequency, decreases the amplitude of the hippocampal-prefrontal cortex postsynaptic synaptic response. The present study demonstrates the importance of the integrity of the mesoc ortical dopaminergic system for long-term potentiation to occur in the hipp ocampal-prefrontal cortex pathway and suggests a frequency-dependent effect of dopamine on hippocampal-prefrontal cortex transmission. (C) 1999 IBRO. Published by Elsevier Science Ltd.