Zepeda Angelica, Sengpiel Frank, Guagnelli Miguel Angel, Vaca Luis, Arias Clorinda
Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, 04510-México, Distrito Federal, México.
J Neurosci. 2004 Feb 25;24(8):1812-21. doi: 10.1523/JNEUROSCI.3213-03.2004.
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 alpha1 (GABA(A)alpha1), 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(A)alpha1 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.
局灶性视觉皮层损伤后皮质表征的重组已有文献记载。有人提出,功能重组可能依赖于涉及兴奋性/抑制性神经传递平衡改变的细胞机制以及损伤周边神经元的形态变化。我们利用内在信号光学成像技术,在小猫初级视觉皮层局灶性缺血损伤后,探索了皮质视网膜拓扑图的功能重组。在损伤后1周、2周和5周(wPL),我们研究了功能重组是否与损伤边界处微管相关蛋白2(MAP-2)、生长相关蛋白43(GAP-43)、胶质纤维酸性蛋白(GFAP)、γ-氨基丁酸A受体α1亚基(GABA(A)α1)、N-甲基-D-天冬氨酸受体1亚基(NMDAR1)的表达变化以及神经递质水平的变化在时间上相关。我们的结果表明:(1)缺血损伤后视网膜拓扑图随时间重组;(2)MAP-2水平从1wPL到5wPL逐渐升高;(3)MAP-2上调与损伤周围树突样结构增加和GFAP阳性细胞减少相关;(4)GAP-43水平在2wPL时达到最高点;(5)NMDAR1和谷氨酸含量从1wPL到5wPL平行增加;(6)GABA(A)α1水平从1wPL到2wPL升高,但在此时间点后不再变化;(7)GABA含量从1wPL到5wPL保持较低水平。这是一项全面的研究,首次表明功能重组在时间上与树突萌发以及先前提出参与皮质重塑的兴奋性/抑制性神经传递系统的变化相关,并提出了皮质表征可塑性可能发生的机制。