5-HT 1A receptor mRNA and immunoreactivity in the rat medial septum/diagonal band of Broca—relationships to GABAergic and cholinergic neurons

Abstract

Activation of 5-HT 1A receptors results in a variety of physiological responses, depending on their localization on neurons with different phenotypes in the brain. This study investigated the localization of 5-HT 1A receptor mRNA and 5-HT 1A receptor immunoreactivity in cell bodies of the rat septal complex using in situ hybridization and immunohistochemistry. In adjacent sections of the medial septum/diagonal band of Broca (MSDB), the distribution of cell bodies expressing 5-HT 1A receptor mRNA was closely related to cells labeled with oligonucleotide probes to GAD (glutamic acid decarboxylase), VAChT (vesicular acetylcholine transporter) or parvalbumin mRNA. Using antiserum to GAD and antibodies to GABA, 5-HT 1A receptor immunoreactivity was demonstrated in a majority of GABAergic cells in the MSDB. 5-HT 1A receptor-immunoreactive GABAergic cells in the MSDB were also demonstrated to contain the calcium-binding protein parvalbumin, a marker for septohippocampal projecting GABAergic neurons. In the lateral septum, 5-HT 1A receptor immunoreactivity was colocalized with the calcium-binding protein calbindin D-28k, a marker for septal GABAergic somatospiny neurons. 5-HT 1A receptor immunoreactivity was also detected in a subpopulation of VAChT-containing cholinergic neurons of the MSDB. In MSDB neurons, colocalization of 5-HT 1A and 5-HT 2A receptor immunoreactivities was demonstrated. These observations suggest that serotonin via 5-HT 1A receptors may represent an important modulator of hippocampal transmission important for cognitive and emotional functions through actions on both GABAergic and cholinergic neurons of the rat septal complex. In addition, 5-HT may exert its effects in the MSDB via cells expressing both 5-HT 1A and 5-HT 2A receptors.