Transgenic mice overexpressing the extracellular domain of NCAM are impaired in working memory and cortical plasticity

NEUROBIOLOGY OF DISEASE

卷:43

Article

Brennaman, Leann H.²  Kochlamazashvili, Gaga¹  Stoenica, Luminita³  Nonneman, Randall J.⁴  Moy, Sheryl S.^4,5  Schachner, Melitta^3,6,7  Dityatev, Alexander^1,3,8  Maness, Patricia F.^2,4 

[1] Italian Inst Technol, Dept Neurosci & Brain Technol, I-16163 Genoa, Italy

[2] Univ N Carolina, Sch Med, Dept Biochem & Biophys, UNC Schizophrenia Res Ctr, Chapel Hill, NC 27599 USA

[3] Univ Med Ctr Hamburg Eppendorf, Zentrum Mol Neurobiol Hamburg, D-20251 Hamburg, Germany

[4] Univ N Carolina, Sch Med, Carolina Inst Dev Disabil, Chapel Hill, NC 27599 USA

[5] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA

[6] Rutgers State Univ, Keck Ctr Collaborat Neurosci, Piscataway, NJ 08854 USA

[7] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ 08854 USA

[8] Univ Med Ctr Hamburg Eppendorf, Inst Neurophysiol & Pathophysiol, D-20246 Hamburg, Germany

关键词: Prefrontal cortex;    NCAM;    Working memory;    Synaptic plasticity;    Neuropsychiatric disorders;    LTP;    STP;   

DOI  :  10.1016/j.nbd.2011.04.008

来源: Elsevier

【 摘 要 】

The neural cell adhesion molecule, NCAM, is a pivotal regulator of neural development, with key roles in axonal and dendritic growth and synaptic plasticity. Alterations in NCAM expression or proteolytic cleavage have been linked to human neuropsychiatric disorders such as schizophrenia, bipolar disorder and Alzheimer's disease, and may contribute to cognitive dysfunction. We have generated mice overexpressing the NCAM extracellular (EC) proteolytic cleavage fragment which has been reported to be increased in schizophrenic versus normal brains. These mice show impaired GABAergic innervation and reduced number of apical dendritic spines on pyramidal neurons in the prefrontal cortex (PFC). Here, these NCAM-EC transgenic mice were subjected to behavioral tasks and electrophysiological measurements to determine the impact of structural abnormalities in the PFC on synaptic and cognitive functions. NCAM-EC mice exhibited impaired working memory in a delayed non-match-to-sample task, which requires PFC function, but showed no differences in anxiety, olfactory abilities, or sociability. Transgenic mice displayed impaired long- and short-term potentiation in the PFC but normal synaptic plasticity in the hippocampus, suggesting that the abnormal synaptic innervation in NCAM-EC mice impairs PFC plasticity and alters working memory. These findings may have implications for cognitive dysfunctions observed in neuropsychiatric disorders. (C) 2011 Elsevier Inc. All rights reserved.

【 授权许可】

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