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

• Published in: Neuroscience Vol. 94; no. 4; pp. 1019 - 1027
• Main Authors: Gurden, H, Tassin, J.-P, Jay, T.M
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.11.1999; Elsevier
• Subjects: Animals; Biological and medical sciences; Central nervous system; Cerebral Cortex - physiology; Dopamine - physiology; dopamine depletion; Electric Stimulation; Electrophysiology; Fundamental and applied biological sciences. Psychology; hippocampus; Hippocampus - physiology; Long-Term Potentiation - physiology; Male; prefrontal cortex; Prefrontal Cortex - physiology; prelimbic; Rats; Rats, Sprague-Dawley; synaptic plasticity; ventral tegmental area; Ventral Tegmental Area - physiology; Vertebrates: nervous system and sense organs; DA, dopamine; hippocampus; VTA, ventral tegmental area; prefrontal cortex; EDTA, ethylenediaminetetra-acetate; LTD, long-term depression; LTP, long-term potentiation; HPLC, high-performance liquid chromatography; 6-OHDA, 6-hydroxydopamine; ventral tegmental area; dopamine depletion; synaptic plasticity; PFC, prefrontal cortex; NMDA, N-methyl- d-aspartate; prelimbic; PKA, protein kinase A; Potentiation; Dopamine; Rat; Rodentia; Central nervous system; Prefrontal cortex; Long term; Vertebrata; Mammalia; Depletion; Synaptic transmission; Synaptic plasticity; Ventral tegmental area; Hippocampus; Brain (vertebrata)
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(99)00395-4

The prefrontal cortex receives dopaminergic inputs from the ventral tegmental 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 cognitive functions we examined the effects of ventral tegmental area stimulation on the induction of long-term potentiation in the hippocampal–prefrontal cortex pathway of anesthetized rats. Stimulation of the ventral tegmental area at a frequency known to evoke dopamine overflow in the prefrontal cortex 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 depletion induced by an electrolytic ventral tegmental area lesion. A significant correlation ( r=0.8; P<0.001; n=14) was obtained between cortical dopamine levels and cortical long-term potentiation amplitude, a depletion of more than 50% of cortical levels corresponding to a dramatic decrease in hippocampal–prefrontal cortex long-term potentiation. However, a recovery to normal long-term potentiation was observed 1 h 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 mesocortical dopaminergic system for long-term potentiation to occur in the hippocampal–prefrontal cortex pathway and suggests a frequency-dependent effect of dopamine on hippocampal–prefrontal cortex transmission.