title: GABAergic projections from the medial septum selectively inhibit interneurons in the medial entorhinal cortex.
abstract: The medial septum (MS) is required for theta rhythmic oscillations and grid cell firing in the medial entorhinal cortex (MEC). While GABAergic, glutamatergic, and cholinergic neurons project from the MS to the MEC, their synaptic targets are unknown. To investigate whether MS neurons innervate specific layers and cell types in the MEC, we expressed channelrhodopsin-2 in mouse MS neurons and used patch-clamp recording in brain slices to determine the response to light activation of identified cells in the MEC. Following activation of MS axons, we observed fast monosynaptic GABAergic IPSPs in the majority (>60%) of fast-spiking (FS) and low-threshold-spiking (LTS) interneurons in all layers of the MEC, but in only 1.5% of nonstellate principal cells (NSPCs) and in no stellate cells. We also observed fast glutamatergic responses to MS activation in a minority (<5%) of NSPCs, FS, and LTS interneurons. During stimulation of MS inputs at theta frequency (10 Hz), the amplitude of GABAergic IPSPs was maintained, and spike output from LTS and FS interneurons was entrained at low (25-60 Hz) and high (60-180 Hz) gamma frequencies, respectively. By demonstrating cell type-specific targeting of the GABAergic projection from the MS to the MEC, our results support the idea that the MS controls theta frequency activity in the MEC through coordination of inhibitory circuits.
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, United Kingdom.
authors.forename: Alfredo
authors.identifier: http://orcid.org/0000-0003-3494-4029
authors.initials: A
authors.lastname: Gonzalez-Sulser
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, United Kingdom.
authors.forename: Daniel
authors.identifier: http://orcid.org/0000-0001-8775-024X
authors.initials: D
authors.lastname: Parthier
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, United Kingdom.
authors.forename: Antonio
authors.initials: A
authors.lastname: Candela
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, United Kingdom.
authors.forename: Christina
authors.initials: C
authors.lastname: McClure
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, United Kingdom.
authors.forename: Hugh
authors.initials: H
authors.lastname: Pastoll
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, United Kingdom.
authors.forename: Derek
authors.initials: D
authors.lastname: Garden
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, United Kingdom.
authors.forename: Gülşen
authors.identifier: http://orcid.org/0000-0002-3227-0641
authors.initials: G
authors.lastname: Sürmeli
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, United Kingdom mattnolan@ed.ac.uk.
authors.forename: Matthew F
authors.identifier: http://orcid.org/0000-0003-1062-6501
authors.initials: MF
authors.lastname: Nolan
mesh_terms: D000818:Animals; D018728:Entorhinal Cortex / Q000166:cytology / Q000502:physiology*; D059330:GABAergic Neurons / Q000502:physiology*; D007395:Interneurons / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000502:physiology*; D012686:Septal Nuclei / Q000166:cytology / Q000502:physiology*
keywords: gamma; interneuron; lamina organization; medial entorhinal cortex; medial septum; theta