Quantitative analysis of glutamatergic and GABAergic neurons expressing 5-HT₂A receptors in human and monkey prefrontal cortex

• Published in: Journal of neurochemistry Vol. 103; no. 2; pp. 475 - 486
• Main Authors: de Almeida, J, Mengod, G
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.10.2007; Blackwell Publishing Ltd; Blackwell
• Subjects: 5-hydroxytryptamine or serotonin 2A; Adult and adolescent clinical studies; antipsychotics; Biochemistry; Biological and medical sciences; Brain; Cellular biology; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; co-localization; DLPFC area 9; Fundamental and applied biological sciences. Psychology; Medical sciences; Mental disorders; Neurology; Neurotransmitters; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; pyramidal neurons; Schizophrenia; Vertebrates: nervous system and sense organs; Calcium; Central nervous system; Glutamatergic neuron; Monkey; Lyases; Serotonine receptor; schizophrenia; Encephalon; Psychosis; Gabaergic receptor; Binding protein; DLPFC area 9; Carboxy-lyases; Modulation; Primates; antipsychotics; Localization; Quantitative analysis; Gabaergic neuron; Human; 5-HT2A serotonin receptor; Decarboxylase; Serotonin; Enzyme; VGLUT1 glutamate transporter; 5-hydroxytryptamine or serotonin 2A; Prefrontal cortex; Parvalbumin; Carbon-carbon lyases; Vertebrata; Mammalia; Neurotransmitter; Mental disorder; pyramidal neurons; co-localization
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2007.04768.x

5-hydroxytryptamine (5-HT) or serotonin 2A receptors play an important role in modulation of prefrontal cortex (PFC) activity and have been implicated in the physiopathology of psychiatric disorders. There is no quantitative information on the percentage of glutamatergic and GABAergic cells that express 5-HT₂A receptors in human and monkey PFC. We have used double in situ hybridization to quantify the mRNA co-localization of 5-HT₂A receptor with the glutamatergic transporter vesicular glutamate transporter 1, and with the GABAergic marker glutamic acid decarboxylase 65/67 and in parvalbumin and calbindin GABAergic cell populations. Our results show that nearly every glutamatergic cell (86-100%) in layers II-V expressed 5-HT₂A receptor mRNA in both species. This percentage was lower in layer VI (13-31%). In contrast, not all the GABAergic interneurons (13-46%) expressed 5-HT₂A receptor mRNA. This receptor was expressed in 45-69% of parvalbumin and in 61-87% of calbindin positive cells. These results indicate that, while the majority of glutamatergic neurons can be sensitive to 5-HT action via 5-HT₂A receptors, this modulation occurs only in a limited population of GABAergic interneurons and provides new neuroanatomical information about the role played by serotonin through 5-HT₂A receptors in the PFC and on the sites of action for drugs such as antipsychotics and antidepressants used in treatment of psychiatric disorders.