title: Optogenetic Activation of Septal Glutamatergic Neurons Drive Hippocampal Theta Rhythms.
abstract: The medial septum and diagonal band of Broca (MS-DBB) has an essential role for theta rhythm generation in the hippocampus and is critical for learning and memory. The MS-DBB contains cholinergic, GABAergic, and recently described glutamatergic neurons, but their specific contribution to theta generation is poorly understood. Here, we examined the role of MS-DBB glutamatergic neurons in theta rhythm using optogenetic activation and electrophysiological recordings performed in in vitro preparations and in freely behaving mice. The experiments in slices suggest that MS-DBB glutamatergic neurons provide prominent excitatory inputs to a majority of local GABAergic and a minority of septal cholinergic neurons. In contrast, activation of MS-DBB glutamatergic fiber terminals in hippocampal slices elicited weak postsynaptic responses in hippocampal neurons. In the in vitro septo-hippocampal preparation, activation of MS-DBB glutamatergic neurons did increase the rhythmicity of hippocampal theta oscillations, whereas stimulation of septo-hippocampal glutamatergic fibers in the fornix did not have an effect. In freely behaving mice, activation of these neurons in the MS-DBB strongly synchronized hippocampal theta rhythms over a wide range of frequencies, whereas activation of their projections to the hippocampus through fornix stimulations had no effect on theta rhythms, suggesting that MS-DBB glutamatergic neurons played a role in theta generation through local modulation of septal neurons. Together, these results provide the first evidence that MS-DBB glutamatergic neurons modulate local septal circuits, which in turn contribute to theta rhythms in the hippocampus.
authors.affiliation: Douglas Mental Health University Institute, McGill University, Department of Psychiatry, Montréal, Québec H4H 1R3, Canada.
authors.forename: Jennifer
authors.identifier: http://orcid.org/0000-0001-9397-432X
authors.initials: J
authors.lastname: Robinson
authors.affiliation: Douglas Mental Health University Institute, McGill University, Department of Psychiatry, Montréal, Québec H4H 1R3, Canada.
authors.forename: Frédéric
authors.identifier: http://orcid.org/0000-0003-3725-9561
authors.initials: F
authors.lastname: Manseau
authors.affiliation: Douglas Mental Health University Institute, McGill University, Department of Psychiatry, Montréal, Québec H4H 1R3, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Ducharme
authors.affiliation: Douglas Mental Health University Institute, McGill University, Department of Psychiatry, Montréal, Québec H4H 1R3, Canada.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Amilhon
authors.affiliation: Douglas Mental Health University Institute, McGill University, Department of Psychiatry, Montréal, Québec H4H 1R3, Canada.
authors.forename: Erika
authors.initials: E
authors.lastname: Vigneault
authors.affiliation: Douglas Mental Health University Institute, McGill University, Department of Psychiatry, Montréal, Québec H4H 1R3, Canada.
authors.forename: Salah
authors.initials: S
authors.lastname: El Mestikawy
authors.affiliation: Douglas Mental Health University Institute, McGill University, Department of Psychiatry, Montréal, Québec H4H 1R3, Canada sylvain.williams@gmail.com.
authors.forename: Sylvain
authors.identifier: http://orcid.org/0000-0002-2511-0631
authors.initials: S
authors.lastname: Williams
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D000075402:Channelrhodopsins; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D020667:Diagonal Band of Broca / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005971:Glutamates / Q000378:metabolism*; D006624:Hippocampus / Q000502:physiology*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials / Q000235:genetics; D051379:Mice; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D062308:Optogenetics; D011810:Quinoxalines / Q000494:pharmacology; D012686:Septal Nuclei / Q000166:cytology*; D016704:Synapsins / Q000235:genetics / Q000378:metabolism; D013826:Theta Rhythm / Q000502:physiology*; D050599:Vesicular Glutamate Transport Protein 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D000075402:Channelrhodopsins; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D008164:Luminescent Proteins; D011810:Quinoxalines; D016704:Synapsins; D050599:Vesicular Glutamate Transport Protein 2; C054562:yellow fluorescent protein, Bacteria; C056723:FG 9041; D002795:Choline O-Acetyltransferase
keywords: glutamatergic; hippocampus; septum; theta