Dopamine favours the emergence of long-term depression versus long-term potentiation in slices of rat prefrontal cortex.

In the present study, we have investigated possible interactions between dopamine and long-term changes in synaptic efficacy induced in layer V pyramidal cells by tetanization of afferents from layer I-II. In the absence of dopamine, we confirmed that high frequency stimulation of excitatory afferents induced long-term potentiation, long-term depression or no change. Inversely, in the presence of dopamine, we have found that the same tetanus led to long-term depression in synaptic transmission in a majority of cells, but no more long-term potentiation. These results suggest that in rat prefrontal cortex, dopamine may determine the direction of activity dependent changes in synaptic efficacy and therefore, plays a functional role in the physiology of this structure.

Dopamine modulation of synaptic transmission in rat prefrontal cortex: an in vitro electrophysiological study.

The prefrontal cortex is innervated by a well-defined dopaminergic bundle originating from the brainstem and is a key structure in higher order mental processes. We have studied the effects of dopamine (DA) on layer V pyramidal cells of the prefrontal cortex using intracellular recording in rat brain slices maintained in vitro. Bath administration of DA (50-100 microM) had weak effects on membrane properties of these neurons. In contrast, DA markedly decreased all components of the synaptic responses evoked by electrical stimulation of layer I or VI, and in particular the monosynaptic excitatory postsynaptic potential (EPSP) which arises from activation of glutamatergic receptors. The afferents from layer VI seemed less affected by DA than those from layer I. The NMDA (N-methyl-D-aspartate) and AMPA (alpha-amino-3-hydroxy-5-methyl-isoxazolepropionic acid) components of monosynaptic EPSPs were equally reduced by DA. The isolated fast gabaergic potential (IPSP) resulting from GABAA receptors activation was similarly reduced by DA. The suppressive effect of DA on glutamatergic transmission was partially mimicked by the D1 receptor agonist SKF 38393 (50 microM) whereas the D2 receptor agonist quinpirole (50 microM) was ineffective. Conversely, this effect was antagonized by the D1 receptor blocker SCH 23390 (100 microM) but not by the D2 receptor antagonist sulpiride (100 microM). These findings indicate that DA decreases both glutamatergic and gabaergic synaptic transmission in neurons located in layer V of rat prefrontal cortex. These results also suggest that D1 dopamine receptor is involved in the decrement of glutamatergic transmission. These interactions between DA and glutamate are important in regard to the suspected implications of both neurotransmitters in psychiatric diseases.

Noradrenaline decreases transmission of NMDA- and non-NMDA-receptor mediated monosynaptic EPSPs in rat prefrontal neurons in vitro.

The effects of noradrenaline on pyramidal cells of layer V of the prefrontal cortex were examined in rat brain slices in vitro. Bath administration of noradrenaline (10 microM) reduced synaptic transmission of afferent inputs from layer 1. The decrease affected all the components of the evoked response and particularly the monosynaptic excitatory postsynaptic potential (EPSP) as evidenced by a reduction of its initial rising slope (mean slope: 71 +/- 11% of its control). Pharmacological dissociation of the NMDA- and non-NMDA-receptor components of the EPSP showed that noradrenaline reduced both (mean EPSP slopes were 71 +/- 8% and 73 +/- 10% of their control, respectively). Alpha 1-, but not alpha-2- or beta-adrenoceptor antagonists prevented the noradrenaline-induced decrease in synaptic efficacy. However, the effect of noradrenaline was not reproduced by alpha 1-adrenoceptor agonists. Lastly, noradrenaline acting through beta-adrenoceptors reduced the slow hyperpolarization that follows a train of action potentials.