Functional Reorganization of Visual Cortex Maps after Ischemic Lesions Is Accompanied by Changes in Expression of Cytoskeletal Proteins and NMDA and GABA_AReceptor Subunits

Abstract

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 A ␣1), 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 ␣1 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 IntroductionCNS as well as PNS lesions lead to functional deficits, yet recovery of the lost functions may occur over time. It has been proposed that restoration of functions after focal somatosensory and motor cortical damage (Nudo et al., 1996a;Rouiller et al., 1998a;Coq and Xerri, 1999;Rijntjes and Weiller, 2002) may rely, to some degree, on the reorganization of cortical maps. Cortical reorganization has been observed to involve either zones surrounding the lesion area (Castro and Borrell, 1995;Nudo et al., 1996a;Rouiller et al., 1998a;Zepeda et al., 1999Zepeda et al., , 2003 or regions within the homologous contralateral cortex (Jones and Schallert, 1992;Jones et al., 1996;Nudo et al., 1996b;Dijkhuizen et al., 2003).Reorganization of the visual cortex after focal lesions has been studied less until recently despite its clinical relevance. We have previously shown that visual cortex maps reorganize to a certain extent with time after an ischemic lesion (Zepeda et al., 2003), while Eysel and Schweigart (1999) have reported that single cells in the surrounding area of the lesion exhibit enlarged receptive fields. However, neurorepair mechanisms associated with such visual reorganizat...

In Vivo Calcium Imaging Reveals Functional Rewiring of Single Somatosensory Neurons after Stroke

“…Comparison with previous studies of plasticity after stroke In patients (Rossini et al, 2007) and animal stroke models (Abo et al, 2001;Dijkhuizen et al, 2001Dijkhuizen et al, , 2003Wei et al, 2001;Zepeda et al, 2003Zepeda et al, , 2004, ipsilesional regional reorganization as observed here is correlated with improved behavioral recovery. In rats with small infarcts, activity within the stroke-affected cortex was required for reaching task performance (Biernaskie et al, 2005).…”

“…Zepeda et al (2004) demonstrated that regional reorganization 5 weeks after photothrombosis correlates with an increase in NMDA-receptor subunit levels from 1-5 weeks after stroke, while GABA levels remain reduced. Anatomically, axonal sprouting in peri-infarct cortex is significantly enhanced for 2 weeks after ischemia (Ng et al, 1988;Stroemer et al, 1995;Li et al, 1998;Carmichael and Chesselet, 2002).…”

Thinning, movement, and volume loss of residual cortical tissue occurs after stroke in the adult rat as identified by histological and magnetic resonance imaging analysis

“…Other work using electrophysiological techniques also finds that peri-infarct tissue moves relative to the infarct location. (Eysel and Schweigart, 1999;Frost et al, 2003;Jenkins and Merzenich, 1987;Reinecke et al, 2003;Schiene et al, 1999;Zepeda et al, 2004).…”

“…In addition, it has been suggested that the compensatory improvements in skilled behavior that occur in the chronic period may be associated with long-lasting plastic changes in residual tissue including changes in neuronal structure, cortical organization, neurotrophic factor regulation, and electrophysiological responsiveness (Eysel and Schweigart, 1999;Schiene et al, 1999;Frost et al, 2003;Gonzalez and Kolb, 2003;Reinecke et al, 2003;Fridman et al, 2004;Zepeda et al, 2004).…”

Improvement of Glucose Metabolism in the Visual Cortex Accompanies Visual Field Recovery in a Patient with Hemianopia

“…A previous animal study reported that cortical retinotopic maps are reorganized following an ischemia, and the plasticity of the functional maps is accompanied by morphological and biochemical modifications in the area surrounding the lesion (Zepeda et al 2003). The increase of FMZ binding in the surrounding areas is in part due to the increase of GABA A receptor density following an ischemia (Zepeda et al 2004).…”