Gao, Xiaoyan ORCID: 0000-0001-8119-529X, Grendel, Jasper, Muhia, Mary, Castro-Gomez, Sergio ORCID: 0000-0002-1581-474X, Suesens, Ute, Isbrandt, Dirk, Kneussel, Matthias, Kuhl, Dietmar ORCID: 0000-0002-4772-6701 and Ohana, Ora (2019). Disturbed Prefrontal Cortex Activity in the Absence of Schizophrenia-Like Behavioral Dysfunction in Arc/Arg3.1 Deficient Mice. J. Neurosci., 39 (41). S. 8149 - 8164. WASHINGTON: SOC NEUROSCIENCE. ISSN 1529-2401

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Abstract

Arc/Arg3.1, an activity regulated immediate early gene, is essential for learning and memory, synaptic plasticity, and maturation of neural networks. It has also been implicated in several neurodevelopmental disorders, including schizophrenia. Here, we used male and female constitutive and conditional Arc/Arg3.1 knock-out (KO) mice to investigate the causal relationship between Arc/Arg3.1 deletion and schizophrenia-linked neurophysiological and behavioral phenotypes. Using in vivo local field potential recordings, we observed dampened oscillatory activity in the prefrontal cortex (PFC) of the KO and early conditional KO (early-cKO) mice, in which Arc/Arg3.1 was deleted perinatally. Whole-cell patch-clamp recordings from neurons in PFC slices revealed altered synaptic properties and reduced network gain in the KO mice as possible mechanisms underlying the oscillation deficits. In contrast, we measured normal oscillatory activity in the PFC of late conditional KO (late-cKO) mice, in which Arc/Arg3.1 was deleted during late postnatal development. Our data show that constitutive Arc/Arg3.1 KO mice exhibit no deficit in social engagement, working memory, sensorimotor gating, native locomotor activity, and dopaminergic innervation. Moreover, adolescent social isolation, an environmental stressor, failed to induce deficits in sociability or sensorimotor gating in adult KO mice. Thus, genetic removal of Arc/Arg3.1 per se does not cause schizophrenia-like behavior. Prenatal or perinatal deletion of Arc/Arg3.1 alters cortical network activity, however, without overtly disrupting the balance of excitation and inhibition in the brain and not promoting schizophrenia. Misregulation of Arc/Arg3.1 rather than deletion could potentially tip this balance and thereby promote emergence of schizophrenia and other neuropsychiatric disorders.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Gao, XiaoyanUNSPECIFIEDorcid.org/0000-0001-8119-529XUNSPECIFIED
Grendel, JasperUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muhia, MaryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Castro-Gomez, SergioUNSPECIFIEDorcid.org/0000-0002-1581-474XUNSPECIFIED
Suesens, UteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Isbrandt, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kneussel, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuhl, DietmarUNSPECIFIEDorcid.org/0000-0002-4772-6701UNSPECIFIED
Ohana, OraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-131200
DOI: 10.1523/JNEUROSCI.0623-19.2019
Journal or Publication Title: J. Neurosci.
Volume: 39
Number: 41
Page Range: S. 8149 - 8164
Date: 2019
Publisher: SOC NEUROSCIENCE
Place of Publication: WASHINGTON
ISSN: 1529-2401
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
LONG-TERM POTENTIATION; IMMEDIATE-EARLY GENE; PREPULSE INHIBITION; MOUSE MODEL; SYNAPTIC PLASTICITY; EPILEPTIC SEIZURES; SPINE MORPHOLOGY; ARC; PROTEIN; EXPRESSIONMultiple languages
NeurosciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13120

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