Dopaminergic modulation of synaptic plasticity in rat prefrontal neurons.

The prefrontal cortex (PFC) is thought to store the traces for a type of long-term memory - the abstract memory that determines the temporal structure of behavior often termed a "rule" or "strategy". Long-term synaptic plasticity might serve as an underlying cellular mechanism for this type of memory. We therefore studied the induction of synaptic plasticity in rat PFC neurons, maintained in vitro, with special emphasis on the functionally important neuromodulator dopamine. First, the induction of long-term potentiation (LTP) was facilitated in the presence of tonic/background dopamine in the bath, and the dose-dependency of this background dopamine followed an "inverted-U" function, where too high or too low dopamine levels could not facilitate LTP. Second, the induction of long-term depression (LTD) by low-frequency stimuli appeared to be independent of background dopamine, but required endogenous, phasically-released dopamine during the stimuli. Blockade of dopamine receptors during the stimuli and exaggeration of the effect of this endogenously-released dopamine by inhibition of dopamine transporter activity both blocked LTD. Thus, LTD induction also followed an inverted-U function in its dopamine-dependency. We conclude that PFC synaptic plasticity is powerfully modulated by dopamine through inverted-U-shaped dose-dependency.