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Prefrontal cortex (PFC) mediates an assortment of cognitive functions including working memory, behavioral flexibility, attention, and future planning. Unlike the hippocampus, where induction of synaptic plasticity in the network is well-documented in relation to long-term memory, cognitive functions mediated by the PFC have been thought to be independent of long-lasting neuronal adaptation of the network. Nonetheless, accumulating evidence suggests that prefrontal cortical neurons possess the cellular machinery of synaptic plasticity and exhibit lasting changes of neural activity associated with various cognitive processes. Moreover, deficits in the mechanisms of synaptic plasticity induction in the PFC might be involved in the pathophysiology of psychiatric and neurological disorders such as schizophrenia, drug addiction, mood disorders, and Alzheimer''s disease. [Copyright &y& Elsevier]

The prefrontal cortex plays a principal role in higher cognition and particularly in the fast online manipulation of appropriate information to guide forthcoming behavior. Dysfunction of this process represents a main feature in the pathophysiology of schizophrenia. Both dopamine D1 and N-methyl-D-aspartate (NMDA) receptors in the prefrontal cortex play a critical role in synaptic plasticity, memory mechanisms, and cognition. Recent data have shown that D1 and NMDA receptors interact bidirectionally and may greatly influence the output of the prefrontal cortex. Hypofunction of these receptor systems in the prefrontal cortex is found in schizophrenia. This review attempts to summarize some of the latest findings on the cellular mechanisms that underlie D1-NMDA receptor interactions. These findings have provided potential therapeutic strategies that aim to functionally up-regulate D1 and/or NMDA receptor safely via selective activation of D1 receptors or coagonist activation of NMDA receptors through blockade of the glycine transporter-1. [ABSTRACT FROM AUTHOR]

The mesocortical dopamine (DA) input to the prefrontal cortex (PFC) is crucial for processing short-term working memory (STWM) to guide forthcoming behavior. Short-term plasticity-like post-tetanic potentiation (PTP, < 3 min) and short-term potentiation (STP, < 10 min) may underlie STWM. Using whole-cell voltage-clamp recordings, mixed glutamatergic excitatory postsynaptic currents (EPSCs) evoked by layer III or layer V stimulation (0.5 or 0.067 Hz) were recorded from layer V pyramidal neurons. With 0.5 Hz basal stimulation of layer III, brief tetani (2 × 50 Hz) induced a homosynaptic PTP (decayed: ∼1 min). The D1-like antagonist SCH23390 (1 µ m) increased the PTP amplitude and decay time without inducing changes to the tetanic response. The tetani may evoke endogenous DA release, which activates a presynaptic D1-like receptor to inhibit glutamate release to modulate PTP. With a slower (0.067 Hz) basal stimulation, the same tetani induced STP (lasting ∼4 min, but only at 2× intensity only) that was insignificantly suppressed by SCH23390. With stimulation of layer-V→V inputs at 0.5 Hz, layer V tetani yielded inconsisitent responses. However, at 0.067 Hz, tetani at double the intensity resulted in an STP (lasting ∼6 min), but a long-term depression after SCH23390 application. Endogenous DA released by tetanic stimulation can interact with a D1-like receptor to induce STP in layer V→V synapses that receive slower (0.067 Hz) frequency inputs, but suppresses PTP at layer III→V synapses that receive higher (0.5 Hz) frequency inputs. This D1-like modulation of layer- and frequency-specific synaptic responses in the PFC may contribute to STWM processing. [ABSTRACT FROM AUTHOR]