Effect Of α_2A-adrenoceptor Simulation On Excitability Of Pyramidal Neurons In Prefrontal Cortex

The prefrontal cortex (PFC) plays a critical role in behaviors requiring a high level of mental integration. Norepinephrine (NE) is a neurotransmitter which is widely distributed throughout the central nervous system. Previous behavioral and physiological studies have demonstrated that NE system exerts an important influence on PFC cognitive functions. Stimulation of α2-, especially α2A-adrenoceptors, in the PFC improves working memory performance. This improvement is accompanied by a selective increase in the activity of prefrontal cortical neurons during delay periods of working memory task. However, the cellular mechanisms responsible for this enhanced response are largely unknown.In the present study, we examined the effect of α2A-adrenoceptor agonist, guanfacine, on action potential in the layer2/3pyramidal cells of PFC of rats using patch clamp whole-cell recording technique. Our results showed that guanfacine increased the spiking number and decreased the latency to spiking; the enhancement induced by guanfacine was occluded by the presence of α2-adrenoceptor antagonist yohimbine; and the enhancement effect still existed when both excitatory and inhibitory synaptic transmission or transmitter release was blocked. These data indicate that guanfacine can enhance intrinsic excitability of the layer2/3pyramidal cells of PFC via stimulating postsynaptic α2A-adrenoceptors.