title: Maternal immune activation differentially impacts mature and adult-born hippocampal neurons in male mice.
abstract: Schizophrenia is associated with deficits in the hippocampus, a brain area important for learning and memory. The dentate gyrus (DG) of the hippocampus develops both before and after birth. To study the relative contribution of mature and adult-born DG granule cells to disease etiology, we compared both cell populations in a mouse model of psychiatric illness resulting from maternal immune activation. Polyriboinosinic-polyribocytidilic acid (PolyIC, 5mg/kg) or saline was given on gestation day 15 to pregnant female C57Bl/6 mice. Male offspring (n=105), was administered systemic bromodeoxyuridine (BrdU, 50mg/kg) (n=52) or intracerebral retroviral injection into the DG (n=53), to label dividing cells at one month of age. Two months later behavioral tests were performed to evaluate disease phenotype. Immunohistochemistry and whole-cell patch clamping were used to assess morphological and physiological characteristics of DG cells. Three-month-old PolyIC exposed male offspring exhibited deficient pre-pulse inhibition, spatial maze performance and motor coordination, as well as increased depression-like behavior. Histological analysis showed reduced DG volume and parvalbumin positive interneuron number. Both mature and new hippocampal neurons showed modifications in intrinsic properties such as increased input resistance and lower current threshold, and decreased action potential number. Reduced GABAergic inhibitory transmission was observed only in mature DG neurons. Differential impairments in mature DG cells and adult-born new neurons may have implications for behavioral deficits associated with maternal immune activation.
authors.affiliation: Neuroplasticity and Behavior Unit, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Neuroplasticity and Behavior Unit, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Electronic address: vanpraagh@mail.nih.gov.
authors.forename: Henriette
authors.initials: H
authors.lastname: van Praag
mesh_terms: D000818:Animals; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000276:immunology; D007369:Interferon Inducers / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000276:immunology*; D009433:Neural Inhibition / Q000187:drug effects / Q000276:immunology; D055495:Neurogenesis / Q000187:drug effects / Q000276:immunology; D009474:Neurons / Q000187:drug effects / Q000276:immunology*; D018408:Patch-Clamp Techniques; D011070:Poly I-C / Q000494:pharmacology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology* / Q000503:physiopathology; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology* / Q000503:physiopathology; D065808:Prepulse Inhibition / Q000187:drug effects / Q000276:immunology*; D012559:Schizophrenia / Q000276:immunology / Q000503:physiopathology; D055139:Sensory Gating / Q000187:drug effects / Q000276:immunology
chemical_list: D007369:Interferon Inducers; D011070:Poly I-C
keywords: Adult neurogenesis; Cognition; Electrophysiology; Hippocampus; Prenatal infection