title: Functional consequences of hippocampal neuronal ectopia in the apolipoprotein E receptor-2 knockout mouse.
abstract: Little is known about the impact ectopically located neurons have on the functional connectivity of local circuits. The ApoER2 knockout mouse has subtle cytoarchitectural disruptions, altered prepulse inhibition, and memory abnormalities. We evaluated this mouse mutant as a model to study the role ectopic neurons play in the manifestation of symptoms associated with brain diseases. We found that ectopic CA1 pyramidal and inhibitory neurons in the ApoER2 knockout hippocampus are organized into two distinct stratum pyramidale layers. In vitro analyses found that ApoER2 is not required for neurons to reach maturity in regard to dendritic arborization and synaptic structure density, and electrophysiological testing determined that neurons in both strata pyramidale are integrated into the hippocampal network. However, the presence of these two layers alters the spatiotemporal pattern of hippocampal activity, which may explain why ApoER2 knockout mice have selective cognitive dysfunctions that are revealed only under challenging conditions.
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Biomedical Science Tower, Pittsburgh, PA 15213, USA. fishkn@umpc.edu
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Fish
authors.forename: Thomas
authors.initials: T
authors.lastname: Krucker
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000002:abnormalities* / Q000473:pathology / Q000503:physiopathology*; D026502:LDL-Receptor Related Proteins; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009474:Neurons / Q000473:pathology* / Q000502:physiology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000473:pathology* / Q000502:physiology; D011973:Receptors, LDL / Q000378:metabolism; D018110:Receptors, Lipoprotein / Q000235:genetics* / Q000378:metabolism
chemical_list: D026502:LDL-Receptor Related Proteins; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; C036053:VLDL receptor; C098773:low density lipoprotein receptor-related protein 8
references.citation: Nature. 1997 Oct 16;389(6652):733-7
references.pmid: 9338785
references.citation: Science. 2002 Oct 25;298(5594):789-91
references.pmid: 12399581
references.citation: Exp Neurol. 2002 Jul;176(1):12-24
references.pmid: 12093079
references.citation: Brain Res. 1994 Oct 31;662(1-2):60-8
references.pmid: 7859091
references.citation: Neuron. 2000 Apr;26(1):197-205
references.pmid: 10798404
references.citation: Neuron. 2000 Feb;25(2):449-57
references.pmid: 10719898
references.citation: J Comp Neurol. 1973 Sep 15;151(2):113-20
references.pmid: 4744470
references.citation: Brain Res. 2007 Oct 3;1172:1-9
references.pmid: 17825270
references.citation: Annu Rev Neurosci. 2002;25:409-32
references.pmid: 12052915
references.citation: Nature. 1995 Apr 20;374(6524):719-23
references.pmid: 7715726
references.citation: J Neurosci. 2002 Jul 1;22(13):5525-35
references.pmid: 12097504
references.citation: Neuroscience. 1998 Apr;83(3):691-700
references.pmid: 9483553
references.citation: Trends Neurosci. 2001 Aug;24(8):479-86
references.pmid: 11476888
references.citation: J Comp Neurol. 1979 Jun 1;185(3):393-422
references.pmid: 438366
references.citation: Cereb Cortex. 1999 Sep;9(6):551-61
references.pmid: 10498273
references.citation: J Autism Dev Disord. 2001 Dec;31(6):529-35
references.pmid: 11814262
references.citation: Neuropharmacology. 2007 Mar;52(4):1114-23
references.pmid: 17261317
references.citation: J Biol Chem. 2002 Oct 18;277(42):39944-52
references.pmid: 12167620
references.citation: Hippocampus. 1991 Jan;1(1):67-78
references.pmid: 1669343
references.citation: Cell. 1999 Jun 11;97(6):689-701
references.pmid: 10380922
references.citation: Neurosci Lett. 1989 Sep 25;104(1-2):58-64
references.pmid: 2554222
references.citation: J Neurosci. 2004 Apr 14;24(15):3770-6
references.pmid: 15084657
references.citation: Cell. 2007 Jan 12;128(1):29-43
references.pmid: 17218253
references.citation: Nature. 1974 Nov 8;252(5479):153-5
references.pmid: 4421774
references.citation: Neuron. 1999 Oct;24(2):481-9
references.pmid: 10571241
references.citation: AMA Arch Neurol Psychiatry. 1959 Mar;81(3):363-9
references.pmid: 13626287
references.citation: Neuron. 2004 Jan 8;41(1):71-84
references.pmid: 14715136
references.citation: Nat Rev Neurosci. 2000 Dec;1(3):181-90
references.pmid: 11257906
references.citation: Nature. 1997 Oct 16;389(6652):730-3
references.pmid: 9338784
references.citation: Development. 1998 Sep;125(18):3719-29
references.pmid: 9716537
references.citation: Cytometry A. 2004 Apr;58(2):167-76
references.pmid: 15057970
references.citation: Am J Psychiatry. 2002 Dec;159(12):2000-6
references.pmid: 12450948
references.citation: Neuron. 1995 May;14(5):899-912
references.pmid: 7748558
references.citation: Behav Neurosci. 2007 Oct;121(5):1101-5
references.pmid: 17907841
references.citation: Hippocampus. 2001;11(5):520-8
references.pmid: 11732705