Effects of Digesting Chondroitin Sulfate Proteoglycans on Plasticity in Cat Primary Visual Cortex

Abstract

Monocular deprivation (MD) during a critical period of postnatal development produces significant changes in the anatomy and physiology of the visual cortex, and the deprived eye becomes amblyopic. Extracellular matrix molecules have a major role in restricting plasticity such that the ability to recover from MD decreases with age. Chondroitin sulfate proteoglycans (CSPGs) act as barriers to cell migration and axon growth. Previous studies showing that degradation of CSPGs by the bacterial enzyme chondroitinase can restore plasticity in the adult rat visual cortex suggest a potential treatment for amblyopia.Here MD was imposed in cats from the start of the critical period until 3.5 months of age. The deprived eye was reopened, the functional architecture of the visual cortex was assessed by optical imaging of intrinsic signals, and chondroitinase was injected into one hemisphere. Imaging was repeated 1 and 2 weeks postinjection, and visually evoked potentials (VEPs) and single-cell activity were recorded.Immunohistochemistry showed that digestion of CSPGs had been successful. After 2 weeks of binocular exposure, some recovery of deprived-eye responses occurred when chondroitinase had been injected into the hemisphere contralateral to that eye; when injected into the ipsilateral hemisphere, no recovery was seen. Deprived-eye VEPs were no larger in the injected hemisphere than in the opposite hemisphere. The small number of neurons dominated by the deprived eye exhibited poor tuning characteristics.These results suggest that despite structural effects of chondroitinase in adult cat V1, plasticity was not sufficiently restored to enable significant functional recovery of the deprived eye.

Activation of perineuronal net-expressing excitatory neurons during associative memory encoding and retrieval

“…For example, PNN degradation allows the induction of long-term potentiation in the hippocampal CA2 area where plasticity is normally limited5, and, likewise, the enhancement of long-term depression in the perirhinal cortex8. By contrast, the digestion of PNNs leads to the impairment of long-term potentiation at thalamo-LA synapses7 and the absence of enhanced plasticity in the feline visual cortex24. Since the types of PNN-expressing neurons differ according to the brain region, cell type-specific degradation of PNNs could provide insight into how PNNs play a role in plasticity, including fear memory.…”

Neuronal Plasticity: Beyond the Critical Period

“…In contrast, in the mouse, with its ''salt and pepper'' type organization for OD (Mrsic-Flogel et al, 2007), the next potential synaptic partner driven by the other eye is just a few micrometers away. Thus, as already pointed out above, an important factor determining the degree of plasticity in the adult brain may simply be the distance between neuronal elements that needs to be bridged between different inputs (Vorobyov et al, 2013). It would be very interesting to test, in adult rats, but also in other animals with OD columns, whether neurons located near the border regions of the columns show a higher degree of plasticity then elsewhere in the visual cortex.…”

Effects of Ethanol on Brain Extracellular Matrix: Implications for Alcohol Use Disorder

“…During development, PNs condense around neurons in an activity‐dependent manner at the end of synaptogenesis. A well‐studied example is in the visual cortex, where PNs form around neurons during the closure of the critical window of visual system development, when ocular dominance plasticity due to monocular deprivation ends (Pizzorusso et al., ; Vorobyov et al., ). Aggrecan is essential to the formation of PNs, and its expression is induced by neuronal activity (Giamanco and Matthews, ; Giamanco et al., ).…”