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The Journal of Neuroscience, February 25, 2004, 24(8):1812-1821; doi:10.1523/JNEUROSCI.3213-03.2004

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Development/Plasticity/Repair
Functional Reorganization of Visual Cortex Maps after Ischemic Lesions Is Accompanied by Changes in Expression of Cytoskeletal Proteins and NMDA and GABA_A Receptor Subunits

Angelica Zepeda,^1,3 Frank Sengpiel,^3,4 Miguel Angel Guagnelli,¹ Luis Vaca,² and Clorinda Arias¹

¹Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, ²Departamento de Biología Celular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510-México, Distrito Federal, México, ³Max-Planck-Institut für Neurobiologie, 82152 München-Martinsried, Germany, and ⁴Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3US, United Kingdom

Reorganization of cortical representations after focal visual cortex lesions has been documented. It has been suggested that functional reorganization may rely on cellular mechanisms involving modifications in the excitatory/inhibitory neurotransmission balance and on morphological changes of neurons peripheral to the lesion. We explored functional reorganization of cortical retinotopic maps after a focal ischemic lesion in primary visual cortex of kittens using optical imaging of intrinsic signals. After 1, 2, and 5 weeks postlesion (wPL), we addressed whether functional reorganization correlated in time with changes in the expression of MAP-2, GAP-43, GFAP, GABA_A receptor subunit 1 (GABA_A1), subunit 1 of the NMDA receptor (NMDAR1), and in neurotransmitter levels at the border of the lesion. Our results show that: (1) retinotopic maps reorganize with time after an ischemic lesion; (2) MAP-2 levels increase gradually from 1wPL to 5wPL; (3) MAP-2 upregulation is associated with an increase in dendritic-like structures surrounding the lesion and a decrease in GFAP-positive cells; (4) GAP-43 levels reach the highest point at 2wPL; (5) NMDAR1 and glutamate contents increase in parallel from 1wPL to 5wPL; (6) GABA_A1 levels increase from 1wPL to 2wPL but do not change after this time point; and (7) GABA contents remain low from 1wPL to 5wPL. This is a comprehensive study showing for the first time that functional reorganization correlates in time with dendritic sprouting and with changes in the excitatory/inhibitory neurotransmission systems previously proposed to participate in cortical remodeling and suggests mechanisms by which plasticity of cortical representations may occur.

Key words: plasticity; visual cortex; sprouting; maps; ischemia; injury; imaging techniques; cat; retinotopy; receptors; photochemical lesion; unmasking

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Received July 7, 2003; revised November 25, 2003; accepted November 25, 2003.

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