QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, May 4, 2005, 25(18):4659-4671; doi:10.1523/JNEUROSCI.0565-05.2005

This Article Full Text Full Text (PDF) Supplemental data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (33) Citing Articles via Google Scholar Google Scholar Articles by Pillai-Nair, N. Articles by Maness, P. F. Search for Related Content PubMed PubMed Citation Articles by Pillai-Nair, N. Articles by Maness, P. F.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Neural Cell Adhesion Molecule-Secreting Transgenic Mice Display Abnormalities in GABAergic Interneurons and Alterations in Behavior

Neeta Pillai-Nair,¹ Anitha K. Panicker,¹ Ramona M. Rodriguiz,² Kelly L. Gilmore,¹ Galina P. Demyanenko,¹ Josh Z. Huang,³ William C. Wetsel,² and Patricia F. Maness¹

¹Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7260, ²Departments of Psychiatry and Behavioral Sciences, Cell Biology, and Medicine (Endocrinology), Mouse Behavioral and Neuroendocrine Analysis Core Facility, Duke University Medical Center, Durham, North Carolina 27710, and ³Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724

The extracellular region of the transmembrane neural cell adhesion molecule (NCAM-EC) is shed as a soluble fragment at elevated levels in the schizophrenic brain. A novel transgenic mouse line was generated to identify consequences on cortical development and function of expressing soluble NCAM-EC from the neuron-specific enolase promoter in the developing and mature neocortex and hippocampus. NCAM-EC transgenic mice exhibited a striking reduction in synaptic puncta of GABAergic interneurons in the cingulate, frontal association cortex, and amygdala but not hippocampus, as shown by decreased immunolabeling of glutamic acid decarboxylase-65 (GAD65), GAD67, and GABA transporter 1. Interneuron cell density was unaltered in the transgenic mice. Affected subpopulations of interneurons included basket interneurons evident in NCAM-EC transgenic mice intercrossed with a reporter line expressing green fluorescent protein and by parvalbumin staining. In addition, there appeared to be a reduction in excitatory synapses, as revealed by synaptophysin staining and apical dendritic spine density of cortical pyramidal cells. Behavioral analyses demonstrated higher basal locomotor activity of NCAM-EC mice and enhanced responses to amphetamine and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate compared with wild-type controls. Transgenic mice were deficient in prepulse inhibition, which was restored by clozapine but not by haloperidol. Additionally, NCAM-EC mice were impaired in contextual and cued fear conditioning. These results suggested that elevated shedding of NCAM perturbs synaptic connectivity of GABAergic interneurons and produces abnormal behaviors that may be relevant to schizophrenia and other neuropsychiatric disorders.

Key words: neural cell adhesion molecule; NCAM; interneuron; GABAergic; cingulate; prepulse inhibition; schizophrenia

---

Received July 7, 2004; revised March 24, 2005; accepted March 26, 2005.

This article has been cited by other articles:

				M.-F. Xiao, J.-C. Xu, Y. Tereshchenko, D. Novak, M. Schachner, and R. Kleene Neural Cell Adhesion Molecule Modulates Dopaminergic Signaling and Behavior by Regulating Dopamine D2 Receptor Internalization J. Neurosci., November 25, 2009; 29(47): 14752 - 14763. [Abstract] [Full Text] [PDF]

				M. van den Buuse Modeling the Positive Symptoms of Schizophrenia in Genetically Modified Mice: Pharmacology and Methodology Aspects Schizophr Bull, November 9, 2009; (2009) sbp132v1. [Abstract] [Full Text] [PDF]

				K. Y. Tseng, B. L. Lewis, T. Hashimoto, S. R. Sesack, M. Kloc, D. A. Lewis, and P. O'Donnell A Neonatal Ventral Hippocampal Lesion Causes Functional Deficits in Adult Prefrontal Cortical Interneurons J. Neurosci., November 26, 2008; 28(48): 12691 - 12699. [Abstract] [Full Text] [PDF]

				N. Sakae, N. Yamasaki, K. Kitaichi, T. Fukuda, M. Yamada, H. Yoshikawa, T. Hiranita, Y. Tatsumi, J.-i. Kira, T. Yamamoto, et al. Mice lacking the schizophrenia-associated protein FEZ1 manifest hyperactivity and enhanced responsiveness to psychostimulants Hum. Mol. Genet., October 15, 2008; 17(20): 3191 - 3203. [Abstract] [Full Text] [PDF]

				R. Batista-Brito, R. Machold, C. Klein, and G. Fishell Gene Expression in Cortical Interneuron Precursors is Prescient of their Mature Function Cereb Cortex, October 1, 2008; 18(10): 2306 - 2317. [Abstract] [Full Text] [PDF]

				S. Diestel, D. Schaefer, H. Cremer, and B. Schmitz NCAM is ubiquitylated, endocytosed and recycled in neurons J. Cell Sci., November 15, 2007; 120(22): 4035 - 4049. [Abstract] [Full Text] [PDF]

				H.-S. Huang, A. Matevossian, C. Whittle, S. Y. Kim, A. Schumacher, S. P. Baker, and S. Akbarian Prefrontal Dysfunction in Schizophrenia Involves Mixed-Lineage Leukemia 1-Regulated Histone Methylation at GABAergic Gene Promoters J. Neurosci., October 17, 2007; 27(42): 11254 - 11262. [Abstract] [Full Text] [PDF]

				O. Senkov, M. Sun, B. Weinhold, R. Gerardy-Schahn, M. Schachner, and A. Dityatev Polysialylated Neural Cell Adhesion Molecule Is Involved in Induction of Long-Term Potentiation and Memory Acquisition and Consolidation in a Fear-Conditioning Paradigm. J. Neurosci., October 18, 2006; 26(42): 10888 - 109898. [Abstract] [Full Text] [PDF]

				V. Sytnyk, I. Leshchyns'ka, A. G. Nikonenko, and M. Schachner NCAM promotes assembly and activity-dependent remodeling of the postsynaptic signaling complex J. Cell Biol., September 25, 2006; 174(7): 1071 - 1085. [Abstract] [Full Text] [PDF]

				B. Weinhold, R. Seidenfaden, I. Rockle, M. Muhlenhoff, F. Schertzinger, S. Conzelmann, J. D. Marth, R. Gerardy-Schahn, and H. Hildebrandt Genetic Ablation of Polysialic Acid Causes Severe Neurodevelopmental Defects Rescued by Deletion of the Neural Cell Adhesion Molecule J. Biol. Chem., December 30, 2005; 280(52): 42971 - 42977. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help