Cerebral Cortex Advance Access originally published online on November 10, 2004
Cerebral Cortex 2005 15(7):950-962; doi:10.1093/cercor/bhh195
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Cerebral Cortex V 15 N 7 © Oxford University Press 2004; all rights reserved
Structural and Functional Aberrations in the Cerebral Cortex of Tenascin-C Deficient Mice
1 Zentrum für Molekulare Neurobiologie, Universität Hamburg, D-20246 Hamburg, Germany and 2 Department of Morphology, University Medical Center, 1 rue Michel Servet, CH-1211 Geneva 4, Switzerland, 3 Present address: Institute of Anatomy and Cell Biology, Albert-Ludwigs-Universität Freiburg, D-79104 Freiburg, Germany, 4 Present address: Prefargier Psychiatric Hospital, CH-2074 Marin, Neuchatel, Switzerland
Address correspondence to Melitta Schachner, Zentrum für Molekulare Neurobiologie, Universität Hamburg, D-20246 Hamburg, Germany. Email: melitta.schachner{at}zmnh.uni-hamburg.de.
The extracellular matrix glycoprotein tenascin-C (TNC) has been implicated in neural development and plasticity but many of its functions in vivo remain obscure. Here we addressed the question as to whether the constitutive absence of TNC in mice affects cortical physiology and structure. Defined major cell populations (neurons and inhibitory neuronal subpopulations, astrocytes, oligodendrocytes and microglia) were quantified in the somatosensory and motor cortices of adult TNC deficient (TNC–/–) and wild-type (TNC+/+) mice by immunofluorescence labelling and stereology. In both areas studied we found abnormally high neuronal density, astrogliosis, low density of parvalbumin-positive interneurons and reduced ratios of oligodendrocytes to neurons and of inhibitory to excitatory neurons in the TNC deficient as opposed to the non-deficient animals. Analysis of Golgi-impregnated layer V pyramidal neurons in TNC–/– animals showed aberrant dendrite tortuosity and redistribution of stubby spines within first- to third-order dendritic arbors. Significantly enhanced responses upon whisker stimulation were recorded epicranially over the barrel and the motor cortices of TNC–/– as compared to TNC+/+ animals, and this effect might be associated with the diminished inhibitory circuitry. These results indicate that TNC is essential for normal cortical development and function.
Key Words: cell density • cerebral cortex • immunohistochemistry • somatosensory evoked potentials • tenascin-C deficient mice
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