title: The hippocamposeptal pathway generates rhythmic firing of GABAergic neurons in the medial septum and diagonal bands: an investigation using a complete septohippocampal preparation in vitro.
abstract: The medial septum diagonal band area (MS/DB) projects to the hippocampus through the fornix/fimbria pathway and is implicated in generating hippocampal theta oscillations. The hippocampus also projects back to the MS/DB, but very little is known functionally about this input. Here, we investigated the physiological role of hippocamposeptal feedback to the MS/DB in a complete in vitro septohippocampal preparation containing the intact interconnecting fornix/fimbria pathway. We demonstrated that carbachol-induced rhythmic theta-like hippocampal oscillations recorded extracellularly were synchronized with powerful rhythmic IPSPs in whole-cell recorded MS/DB neurons. Interestingly, we found that these IPSPs evoked rebound spiking in GABAergic MS/DB neurons. In contrast, putative cholinergic and glutamatergic MS/DB neurons responded only weakly with rebound spiking and, as a result, were mostly silent during theta-like oscillations. We next determined the mechanism underlying the rebound spiking that followed the IPSPs in MS/DB GABAergic neurons using phasic electrical stimulation of the fornix/fimbria pathway. We demonstrate that the increased rebound spiking was attributable to the activation of I(h) current, because it was significantly reduced by low concentrations of the I(h) antagonist ZD7288 [4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyridinium chloride]. Together, these results suggest that rhythmical activity in hippocampus is transferred to the MS/DB and can preferentially phase the spiking of GABAergic MS/DB neurons because of their significant expression of I(h) currents. Our data demonstrate that hippocamposeptal inhibition facilitates theta rhythmic discharges in MS/DB GABAergic neurons while favoring the inhibition of most ACh and glutamate neurons.
authors.affiliation: Douglas Hospital Research Center, Department of Psychiatry, McGill University, Montreal, Quebec, Canada H4H 1R3. f.manseau@ebri.it
authors.forename: Frédéric
authors.initials: F
authors.lastname: Manseau
authors.forename: Romain
authors.initials: R
authors.lastname: Goutagny
authors.forename: Marc
authors.initials: M
authors.lastname: Danik
authors.forename: Sylvain
authors.initials: S
authors.lastname: Williams
mesh_terms: D000200:Action Potentials; D000818:Animals; D000831:Animals, Newborn; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D020667:Diagonal Band of Broca / Q000166:cytology / Q000502:physiology*; D004558:Electric Stimulation; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials; D009433:Neural Inhibition / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D009991:Oscillometry; D010507:Periodicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D012686:Septal Nuclei / Q000166:cytology / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018679:Cholinergic Agonists; D005680:gamma-Aminobutyric Acid; D002217:Carbachol