Brain Research 989 (2003) 42–51 www.elsevier.com / locate / brainres Research report Serotonin 5-HT1A receptors might control the output of cortical glutamatergic neurons in rat cingulate cortex † ´ Anna Czyrak , Klaudia Czepiel, Marzena Mackowiak, Agnieszka Chocyk, * Krzysztof We ˛dzony Laboratory of Pharmacology and Brain Biostructure, Institute of Pharmacology, Polish Academy of Sciences, 12 Sme ¸tna Street, 31-343 Krakow, Poland Accepted 24 June 2003 Abstract The present study was designed to investigate the distribution of serotonin 5-HT1A receptor protein (5-HT1A-immunoreactivity) and its localization within cortical pyramidal neurons of the rat cingulate cortex. This experimental direction was inspired by recent data showing the role of 5-HT1A receptors in the pathology of schizophrenia, and in the mechanism of action of novel antipsychotic drugs as well as by the importance of the cingulate cortex in regulation of cognitive functions. It was found that 5-HT1A-immunoreactivity was densely distributed in neuronal eyelash-like elements, and their size, shape and spatial orientation may suggest concentration of 5-HT1A-immunopositive material in the proximal fragments of axons of cortical neurons. Moreover, it was observed that these 5-HT1A-immunopositive fragments were present predominately on proximal fragments of axons of pyramidal neurons, which was evidenced by double labeling experiments using glutamate and non-phosphorylated neurofilament H as markers of the cortical pyramidal cells. The 5-HT1A receptor immunoreactivity was localized distally to the inhibitory GABAergic terminals of chandelier and basket cells surrounding the pyramidal cell bodies and occasionally surrounding short initial segment of axonal hillock of pyramidal neurons. These anatomical data indicate that 5-HT1A receptors might control the excitability and propagation of information transmitted by the pyramidal cells. Moreover, our results indicate that drugs operating via 5-HT1A receptors in the cingulate cortex might control from this level the release of glutamate in the subcortical structures. Finally, the 5-HT1A receptors present in the cingulate cortex, as demonstrated in the present study, may constitute an important target for drugs used to repair dysfunction of glutamate neurotransmission, which is observed for example in schizophrenia.  2003 Elsevier B.V. All rights reserved. Theme: Neurotransmitters, modulators, transporters, and receptors Topic: Serotonin receptors Keywords: 5-HT1A Receptor; Neurofilament H; Parvalbumin; Glutamate; Double labeling; Immunohistochemistry 1. Introduction zation due to the opening of potassium channels [57,64]. The highest density of 5-HT1A receptors has been ob- The serotonin 5-HT1A receptors belong to a subtype of served in the cerebral cortex, hippocampus and raphe metabotropic receptors, negatively coupled to adenylate nuclei [14,17,18,56,66,69]. Their functional role has been cyclase [30]. Their activation elicits neuronal hyperpolari- extensively investigated because of their involvement in psychopathological states such as depression and anxiety [7,19]. Recently, it has been postulated that 5-HT1A *Corresponding author. Tel.: 148-12-662-3253; fax: 148-12-637- receptors might also be involved in the pathophysiology of 4500. schizophrenia [6] and, subsequently, that they may repre- E-mail address: nfwedzon@cyf-kr.edu.pl (K. We ˛dzony). sent a novel target for antipsychotic compounds [6,47]. † This is the last paper written by Dr Anna Czyrak who died shortly before The assumption that these receptors are involved in the submission of the manuscript. Her unexpected death is a painful and pathomechanism of schizophrenia is based on the observa- irreparable loss for us. Her passing bereaved us of an open-hearted and open-minded person, a distinguished scientist and an unforgettable friend. tions that the density of 5-HT1A receptors is elevated in 0006-8993 / 03 / $ – see front matter  2003 Elsevier B.V. All rights reserved. doi:10.1016 / S0006-8993(03)03352-3