title: Functional Architecture of the Rat Parasubiculum.
abstract: The parasubiculum is a major input structure of layer 2 of medial entorhinal cortex, where most grid cells are found. Here we investigated parasubicular circuits of the rat by anatomical analysis combined with juxtacellular recording/labeling and tetrode recordings during spatial exploration. In tangential sections, the parasubiculum appears as a linear structure flanking the medial entorhinal cortex mediodorsally. With a length of ∼5.2 mm and a width of only ∼0.3 mm (approximately one dendritic tree diameter), the parasubiculum is both one of the longest and narrowest cortical structures. Parasubicular neurons span the height of cortical layers 2 and 3, and we observed no obvious association of deep layers to this structure. The "superficial parasubiculum" (layers 2 and 1) divides into ∼15 patches, whereas deeper parasubicular sections (layer 3) form a continuous band of neurons. Anterograde tracing experiments show that parasubicular neurons extend long "circumcurrent" axons establishing a "global" internal connectivity. The parasubiculum is a prime target of GABAergic and cholinergic medial septal inputs. Other input structures include the subiculum, presubiculum, and anterior thalamus. Functional analysis of identified and unidentified parasubicular neurons shows strong theta rhythmicity of spiking, a large fraction of head-direction selectivity (50%, 34 of 68), and spatial responses (grid, border and irregular spatial cells, 57%, 39 of 68). Parasubicular output preferentially targets patches of calbindin-positive pyramidal neurons in layer 2 of medial entorhinal cortex, which might be relevant for grid cell function. These findings suggest the parasubiculum might shape entorhinal theta rhythmicity and the (dorsoventral) integration of information across grid scales.
  
  
  CONCLUSIONS
  Grid cells in medial entorhinal cortex (MEC) are crucial components of an internal navigation system of the mammalian brain. The parasubiculum is a major input structure of layer 2 of MEC, where most grid cells are found. Here we provide a functional and anatomical characterization of the parasubiculum and show that parasubicular neurons display unique features (i.e., strong theta rhythmicity of firing, prominent head-direction selectivity, and output selectively targeted to layer 2 pyramidal cell patches of MEC). These features could contribute to shaping the temporal and spatial code of downstream grid cells in entorhinal cortex.
authors.affiliation: Bernstein Center for Computational Neuroscience, Humboldt Universität zu Berlin, 10115 Berlin, Germany.
authors.forename: Qiusong
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Werner Reichardt Centre for Integrative Neuroscience, 72076 Tübingen, Germany, andrea.burgalossi@cin.uni-tuebingen.de michael.brecht@bccn-berlin.de.
authors.forename: Andrea
authors.initials: A
authors.lastname: Burgalossi
authors.affiliation: Bernstein Center for Computational Neuroscience, Humboldt Universität zu Berlin, 10115 Berlin, Germany, Berlin School of Mind and Brain, Humboldt University of Berlin, 10115 Berlin, Germany, and.
authors.forename: Christian Laut
authors.initials: CL
authors.lastname: Ebbesen
authors.affiliation: Bernstein Center for Computational Neuroscience, Humboldt Universität zu Berlin, 10115 Berlin, Germany.
authors.forename: Juan Ignacio
authors.initials: JI
authors.lastname: Sanguinetti-Scheck
authors.affiliation: Bernstein Center for Computational Neuroscience, Humboldt Universität zu Berlin, 10115 Berlin, Germany.
authors.forename: Helene
authors.initials: H
authors.lastname: Schmidt
authors.affiliation: Bernstein Center for Computational Neuroscience, Humboldt Universität zu Berlin, 10115 Berlin, Germany, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany.
authors.forename: John J
authors.identifier: http://orcid.org/0000-0002-4394-199X
authors.initials: JJ
authors.lastname: Tukker
authors.affiliation: Bernstein Center for Computational Neuroscience, Humboldt Universität zu Berlin, 10115 Berlin, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Naumann
authors.affiliation: Bernstein Center for Computational Neuroscience, Humboldt Universität zu Berlin, 10115 Berlin, Germany.
authors.forename: Saikat
authors.initials: S
authors.lastname: Ray
authors.affiliation: Werner Reichardt Centre for Integrative Neuroscience, 72076 Tübingen, Germany.
authors.forename: Patricia
authors.initials: P
authors.lastname: Preston-Ferrer
authors.affiliation: Charité Universitätsmedizin Berlin, 10117 Berlin, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schmitz
authors.affiliation: Bernstein Center for Computational Neuroscience, Humboldt Universität zu Berlin, 10115 Berlin, Germany, andrea.burgalossi@cin.uni-tuebingen.de michael.brecht@bccn-berlin.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Brecht
mesh_terms: D000818:Animals; D064026:Calbindins / Q000378:metabolism; D049229:Dendritic Spines; D004566:Electrodes; D018728:Entorhinal Cortex / Q000033:anatomy & histology* / Q000166:cytology; D005260:Female; D006624:Hippocampus / Q000033:anatomy & histology* / Q000166:cytology; D008297:Male; D009434:Neural Pathways / Q000033:anatomy & histology / Q000166:cytology; D009474:Neurons / Q000502:physiology; D017966:Pyramidal Cells / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D013028:Space Perception / Q000502:physiology; D013788:Thalamus / Q000033:anatomy & histology / Q000166:cytology; D013826:Theta Rhythm
chemical_list: D064026:Calbindins
keywords: anatomy; border cell; head-direction cell; medial entorhinal cortex; parasubiculum; spatial navigation