Journal
CEREBRAL CORTEX
Volume 19, Issue 11, Pages 2708-2718Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhp047
Keywords
dopamine; ERK; LTD; LTP; prefrontal cortex
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Funding
- Centre National de la Recherche Scientifique (CNRS)
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- University of Paris VI
- French Minister of Research
- The Sophia University Open Research Center Grant
- International Brain Research Organization (IBRO)
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Altered levels of tonic/background dopamine in prefrontal cortex (PFC) may underlie modifications of executive cognitive function. We showed previously in rat PFC slices that exogenously supplied background dopamine facilitates induction of long-term potentiation (LTP), a possible cellular substrate for the long-term component of executive cognitive function. In the present study, we characterized cellular and molecular mechanisms underlying this modulatory dopamine effect. We show first that the LTP-facilitating effect of tonic/background dopamine follows an inverted-U shape concentration curve and that the effective level of background dopamine slowly activates postsynaptic extracellular signal-regulated kinases (ERKs) to facilitate LTP. Furthermore, we show the evidence that LTP-inducing high-frequency stimulation evokes endogenous release of dopamine in PFC slices. This fast dopamine serves as a trigger for LTP in the presence of the background dopamine. In its absence, the endogenous dopamine triggered, instead, long-term depression. These results indicate that appropriate levels of tonic/background dopamine serve to activate critical molecular factors in PFC neurons and thereby facilitate induction of synaptic potentiation.
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