Transgenic mice overexpressing the extracellular domain of NCAM are impaired in working memory and cortical plasticity.
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Transgenic mice overexpressing the extracellular domain of NCAM are impaired in working memory and cortical plasticity. / Brennaman, Leann H; Kochlamazashvili, Gaga; Stoenica, Luminita; Nonneman, Randall J; Moy, Sheryl S; Schachner, Melitta; Dityatev, Alexander; Maness, Patricia F.
In: NEUROBIOL DIS, Vol. 43, No. 2, 2, 2011, p. 372-378.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Transgenic mice overexpressing the extracellular domain of NCAM are impaired in working memory and cortical plasticity.
AU - Brennaman, Leann H
AU - Kochlamazashvili, Gaga
AU - Stoenica, Luminita
AU - Nonneman, Randall J
AU - Moy, Sheryl S
AU - Schachner, Melitta
AU - Dityatev, Alexander
AU - Maness, Patricia F
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - Animals
KW - Male
KW - Female
KW - Disease Models, Animal
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Transgenic
KW - Organ Culture Techniques
KW - Proteolysis
KW - Cerebral Cortex/pathology/physiology
KW - Extracellular Space/genetics/metabolism
KW - Memory Disorders/genetics/metabolism/pathology
KW - Memory, Short-Term/physiology
KW - Neural Cell Adhesion Molecules/biosynthesis/genetics
KW - Neuronal Plasticity/genetics
KW - Neurons/metabolism/pathology
KW - Protein Structure, Tertiary/genetics
KW - Animals
KW - Male
KW - Female
KW - Disease Models, Animal
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Transgenic
KW - Organ Culture Techniques
KW - Proteolysis
KW - Cerebral Cortex/pathology/physiology
KW - Extracellular Space/genetics/metabolism
KW - Memory Disorders/genetics/metabolism/pathology
KW - Memory, Short-Term/physiology
KW - Neural Cell Adhesion Molecules/biosynthesis/genetics
KW - Neuronal Plasticity/genetics
KW - Neurons/metabolism/pathology
KW - Protein Structure, Tertiary/genetics
M3 - SCORING: Journal article
VL - 43
SP - 372
EP - 378
JO - NEUROBIOL DIS
JF - NEUROBIOL DIS
SN - 0969-9961
IS - 2
M1 - 2
ER -
