Control serotoninérgico de la corteza prefrontal

Abstract

The prefrontal cortex (PFC) plays a crucial role in higher brain functions such as working memory or cognition and controls, via the excitatory axons of pyramidal neurons, the activity of many subcortical motor and limbic areas. It receives a dense innervation from the brainstem aminergic nuclei, including the serotonergic raphe nuclei. Prefrontal function and metabolism is altered in patients with severe psychiatric disorders, like major depression or schizophrenia. Although the exact role of serotonergic neurotransmission in PFC remains largely unknown, the PFC contains a very large density or serotonin 5-HT1A (inhibitory) and 5-HT2A (excitatory) receptors. In addition, hallucinogens like LSD or DOI are agonists and atypical antipsychotics are antagonists at 5-HT2A receptors. In this review we focus on the main excitatory and inhibitory mechanisms through which serotonin modulates pyramidal and GABAergic neuron activity in the PFC. We report on the presence of 5-HT1A and 5-HT2A receptor-mediated responses in pyramidal neurons of the PFC that exert opposite effects on their activity when recorded in vivo in the anesthetized rat. Despite the large co-expression of both receptors in pyramidal neurons of the PFC, physiological amounts of 5-HT mainly inhibit pyramidal neurons. This is probably due to the distinct location of 5-HT1A and 5-HT2A in pyramidal neurons. Thus, 5-HT1A receptors are mainly localized in the axon hillock, where they may have a prominent inhibitory role in the control of pyramidal activity given their coupling to GIRK channels. Moreover, 5-HT can inhibit pyramidal neurons indirectly through the activation of 5-HT2A and 5-HT3 receptors localized in GABAergic interneurons and a subsequent increase in synaptic GABA inputs.