title: Frequency-dependent, cell type-divergent signaling in the hippocamposeptal projection.
abstract: Hippocampal oscillations are critical for information processing, and are strongly influenced by inputs from the medial septum. Hippocamposeptal neurons provide direct inhibitory feedback from the hippocampus onto septal cells, and are therefore likely to also play an important role in the circuit; these neurons fire at either low or high frequency, reflecting hippocampal network activity during theta oscillations or ripple events, respectively. Here, we optogenetically target the long-range GABAergic projection from the hippocampus to the medial septum in rats, and thereby simulate hippocampal input onto downstream septal cells in an acute slice preparation. In response to optogenetic activation of hippocamposeptal fibers at theta and ripple frequencies, we elicit postsynaptic GABAergic responses in a subset (24%) of septal cells, most predominantly in fast-spiking cells. In addition, in another subset of septal cells (19%) corresponding primarily to cholinergic cells, we observe a slow hyperpolarization of the resting membrane potential and a decrease in input resistance, particularly in response to prolonged high-frequency (ripple range) stimulation. This slow response is partially sensitive to GIRK channel and D2 dopamine receptor block. Our results suggest that two independent populations of septal cells distinctly encode hippocampal feedback, enabling the septum to monitor ongoing patterns of activity in the hippocampus.
authors.affiliation: Neuroscience Program, Department of Bioengineering.
authors.forename: Joanna
authors.initials: J
authors.lastname: Mattis
authors.affiliation: Department of Neurology and Neurological Science.
authors.forename: Julia
authors.initials: J
authors.lastname: Brill
authors.affiliation: Department of Economics, Mathematics and Statistics, Birkbeck, University of London, Bloomsbury, London WC1E 7HX.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Evans
authors.affiliation: Department of Bioengineering.
authors.forename: Talia N
authors.initials: TN
authors.lastname: Lerner
authors.affiliation: Department of Bioengineering.
authors.forename: Thomas J
authors.identifier: http://orcid.org/0000-0003-0836-6333
authors.initials: TJ
authors.lastname: Davidson
authors.affiliation: Department of Bioengineering.
authors.forename: Minsuk
authors.initials: M
authors.lastname: Hyun
authors.affiliation: Department of Bioengineering.
authors.forename: Charu
authors.identifier: http://orcid.org/0000-0002-3474-6332
authors.initials: C
authors.lastname: Ramakrishnan
authors.affiliation: Department of Bioengineering, Howard Hughes Medical Institute, Department of Psychiatry and Behavioral Sciences, Cracking the Neural Code Program, Stanford University, Stanford, California 94305, and john.huguenard@stanford.edu deissero@stanford.edu.
authors.forename: Karl
authors.initials: K
authors.lastname: Deisseroth
authors.affiliation: Department of Neurology and Neurological Science, john.huguenard@stanford.edu deissero@stanford.edu.
authors.forename: John R
authors.initials: JR
authors.lastname: Huguenard
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000502:physiology*; D007150:Immunohistochemistry; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D009434:Neural Pathways / Q000502:physiology*; D062308:Optogenetics; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D020318:Rats, Long-Evans; D012686:Septal Nuclei / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
keywords: hippocamposeptal; medial septum; optogenetics