title: Synergy of direct and indirect cholinergic septo-hippocampal pathways coordinates firing in hippocampal networks.
abstract: The medial septum/diagonal band of Broca complex (MSDB) is a key structure that modulates hippocampal rhythmogenesis. Cholinergic neurons of the MSDB play a central role in generating and pacing theta-band oscillations in the hippocampal formation during exploration, novelty detection, and memory encoding. How precisely cholinergic neurons affect hippocampal network dynamics in vivo, however, has remained elusive. In this study, we show that stimulation of cholinergic MSDB neurons in urethane-anesthetized mice acts on hippocampal networks via two distinct pathways. A direct septo-hippocampal cholinergic projection causes increased firing of hippocampal inhibitory interneurons with concomitantly decreased firing of principal cells. In addition, cholinergic neurons recruit noncholinergic neurons within the MSDB. This indirect pathway is required for hippocampal theta synchronization. Activation of both pathways causes a reduction in pyramidal neuron firing and a more precise coupling to the theta oscillatory phase. These two anatomically and functionally distinct pathways are likely relevant for cholinergic control of encoding versus retrieval modes in the hippocampus.
authors.affiliation: Laboratory for Experimental Epileptology and Cognition Research, Department of Epileptology.
authors.forename: Holger
authors.identifier: http://orcid.org/0000-0002-0340-0128
authors.initials: H
authors.lastname: Dannenberg
authors.affiliation: Laboratory for Experimental Epileptology and Cognition Research, Department of Epileptology.
authors.forename: Milan
authors.initials: M
authors.lastname: Pabst
authors.affiliation: Laboratory for Experimental Epileptology and Cognition Research, Department of Epileptology.
authors.forename: Oliver
authors.initials: O
authors.lastname: Braganza
authors.affiliation: Section of Translational Epileptology, Institute for Neuropathology, and.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schoch
authors.affiliation: Cognitive and Clinical Electrophysiology, Department of Epileptology, University of Bonn Medical Center, 53105 Bonn, Germany, and.
authors.forename: Johannes
authors.identifier: http://orcid.org/0000-0003-3323-2986
authors.initials: J
authors.lastname: Niediek
authors.affiliation: Cognitive and Clinical Electrophysiology, Department of Epileptology, University of Bonn Medical Center, 53105 Bonn, Germany, and.
authors.forename: Melike
authors.initials: M
authors.lastname: Bayraktar
authors.affiliation: Cognitive and Clinical Electrophysiology, Department of Epileptology, University of Bonn Medical Center, 53105 Bonn, Germany, and.
authors.forename: Florian
authors.initials: F
authors.lastname: Mormann
authors.affiliation: Laboratory for Experimental Epileptology and Cognition Research, Department of Epileptology, Deutsches Zentrum für Neurodegenerative Erkrankungen, 53105 Bonn, Germany heinz.beck@ukb.uni-bonn.de.
authors.forename: Heinz
authors.initials: H
authors.lastname: Beck
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000200:Action Potentials / Q000235:genetics*; D000818:Animals; D000075402:Channelrhodopsins; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D059329:Cholinergic Neurons / Q000187:drug effects / Q000502:physiology; D000229:Dependovirus / Q000235:genetics; D006339:Heart Rate / Q000187:drug effects / Q000235:genetics; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism; D010775:Photic Stimulation; D061088:Photoacoustic Techniques; D012686:Septal Nuclei / Q000502:physiology; D013826:Theta Rhythm / Q000235:genetics / Q000502:physiology; D013997:Time Factors; D014161:Transduction, Genetic
chemical_list: D000075402:Channelrhodopsins; D010320:Parvalbumins; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine
keywords: acetylcholine; encoding; hippocampus; in vivo electrophysiology; medial septum; theta oscillation