Activate ¦Á <sub> 2a </ Sub> - Adrenergic Receptor Promotes Medial Prefrontal Cortical Neurons Mature Dendritic Spines

The prefrontal cortex (PFC) participates the regulation of learning and memory, and plays a vital role in brain function. Deficits in PFC functions are common in many neuropsychiatric disorders. Norepinephrine (NE) exerts a beneficial influence on PFC cognitive functions through actions at postsynaptic alpha-2A-adrenoceptors (α.2A-ARs).α2A-adrenoeceptors is much expressed in cortical neurons and play an important role in neuronal differentiation, growth and neurotrophy. Dendritic spines are tiny protrusions along dendrites that compartmentalize postsynaptic responses in mature brain, and are crucial in synaptic transmission and plasticity. It is known that change in spine morphology is associated with brain functions such as learning and memory.Here, we report that stimulation ofα2A-ARs promotes the maturation of dendritic spines in cultured neurons of the medial prefrontal cortex of rodents. Our results show that,α2A-ARs are expressed in cultured neurons. Stimulation by guanfacine, the selective agonist ofα2A-ARs promotes the growth of dendrites, induces significantly more mushroom spines, and enlarges the area of spine head. In parallel, the cytoskeleton of spines also changed with the morphology alteration, and the expression of post-synaptic protein PSD95 in guanfacine-treated neurons was enhanced, while that of pre-synaptic protein synapsin I was not changed. The guanfacine effects were blocked by co-administered yohimbine, a non-selectiveα-AR antagonist. These results implicate a prominent role ofα2A-ARs in regulating the maturation of dendritic spines in the mPFC.