Excitatory actions of serotonin on GABAergic neurons of the medial septum and diagonal band of Broca.
The physiological and pharmacological actions of serotonin (5-HT) on neurons in the medial septum and diagonal band of Broca (MSDB) were examined using extracellular and intracellular recording techniques in an in vitro rat brain-slice preparation. In addition to previously described inhibitory effects, novel excitatory actions of 5-HT on GABA-type cells were observed. In intracellular recordings with KCl-containing electrodes, bath-applied 5-HT induced a bicuculline and tetrodotoxin-sensitive increase in the number of reverse IPSPs in both cholinergic- and noncholinergic-type neurons (presumably GABAergic). In brain slices where all structures neighboring the MSDB, including the lateral septum, had been excised, a similar increase in 5-HT-induced IPSPs occurred, indicating that 5-HT-induced IPSPs in both cholinergic- and noncholinergic-type neurons originate from GABAergic neurons within the MSDB itself. Accordingly, GABA-type neurons in the MSDB were found to be directly excited by 5-HT. MDL 100,907, a selective 5-HT2A antagonist, blocked 5-HT-induced excitations in a majority of neurons (58%). ICS 205-930, a 5-HT3/5-HT4 antagonist, or mianserin, a nonselective 5-HT antagonist, blocked most MDL-resistant responses, indicating a role for multiple 5-HT receptor subtypes. This study also provides the first electrophysiological evidence for synaptic interactions between 5-HT-activated GABAergic neurons and cholinergic neurons and amongst GABAergic neurons in the MSDB. The implications of the findings vis-à-vis intraseptal circuitry and septohippocampal circuitry are discussed.
Alreja
M
M
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06508, USA.
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005110:Extracellular Space / Q000502:physiology; D005464:Fluorobenzenes / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014795:Visual Pathways / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D005464:Fluorobenzenes; D018756:GABA Antagonists; D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D011189:Potassium Chloride; C079049:volinanserin; D001640:Bicuculline