Changes in NMDA-Receptor Function in the First Week Following Laser-Induced Lesions in Rat Visual Cortex

Abstract

Focal brain injuries are accompanied by processes of functional reorganization that partially compensate the functional loss. In a previous study, extracellular recordings at the border of a laser-induced lesion in the visual cortex of rats showed an enhanced synaptic plasticity, which was mediated by the activity of NR2B-contaning NMDA-receptors (NMDARs) shedding light on the potential cellular mechanisms underlying this reorganization. Given the potentially important contribution of NMDARs in processes of functional reorganization, in the present study, we used the same lesion model to further investigate lesion-induced changes in function and localization of NMDARs in the vicinity of the lesion. The most important finding was a lesion-mediated functional reexpression of nonpostsynaptic, but according to our data, presynaptic or peri-/extrasynaptic NMDARs (preNMDARs), which were undetectable in age-matched (>P21) sham-operated controls. Notably, preNMDARs were able to boost both spontaneous and evoked synaptic glutamatergic transmission. At the postsynaptic site, we also disclosed an increase in the decay time constant of NMDARs mediated currents, which was accompanied by a decreased NR2A/NR2B ratio, as revealed by Western blot analysis. All together these findings provide new insights into the role of NMDARs activity during processes of functional reorganization following a focal lesion in the cerebral cortex.

NO regulates the strength of synaptic inputs onto hippocampal CA1 neurons via NO-GC1/cGMP signalling

“…To decrease the leakage of MK-801 from the recording pipette, the tip was filled with normal intracellular solution and backfilled with MK-801-containg solution, and only low positive pressure was used when approaching the cell. The block of NMDAR activity by intracellular application of MK-801 is a well-established approach and has been used by others before [2,10,30,32] and in our own lab [31]. We observed a significant reduction of the mean sIPSC frequency in WT neurons, whereas NO-GC1KO pyramidal neurons remained completely unaffected.…”

“…Recent evidence indicates that NO/cGMP signalling also exerts positive feedback onto GABAergic transmission and requires the activation of postsynaptic NMDARs [32]. NO-GC1 was observed at presynaptic terminals of GABAergic interneurons, using immunohistochemical approaches, while nNOS was detected at opposing postsynaptic sites of GABAergic synapses on CA1 pyramidal cells [26,27].…”

Population receptive field analysis of the primary visual cortex complements perimetry in patients with homonymous visual field defects

“…possible mechanism behind this shift is enhancement of surviving single-cell pRFs in voxels near the border of the scotoma after injury, perhaps via a change in the balance of inhibition versus excitation (27)(28)(29)(30)(31). The magnitude of the shift is on average only 1°, consistent with at most a limited degree of reorganization.…”

“…As expected, reorganization is more extensive in young animals (23, 25) compared with adults (26). A change in the balance between excitation and inhibition may underlie this functional reorganization (27)(28)(29)(30)(31).In humans, V1 injury is typically followed by a brief period of spontaneous recovery, which rarely lasts beyond 6 mo (32). Whether this recovery is the result of true visual system plasticity or is related to the gradual resolution of perilesional edema and general clinical improvement of the patients is unclear.…”

“…As expected, reorganization is more extensive in young animals (23, 25) compared with adults (26). A change in the balance between excitation and inhibition may underlie this functional reorganization (27)(28)(29)(30)(31).…”