Structural and functional recovery from early monocular deprivation in adult rats

Abstract

Visual deficits caused by abnormal visual experience during development are hard to recover in adult animals. Removal of chondroitin sulfate proteoglycans from the mature extracellular matrix with chondroitinase ABC promotes plasticity in the adult visual cortex. We tested whether chondroitinase ABC treatment of adult rats facilitates anatomical, functional, and behavioral recovery from the effects of a period of monocular deprivation initiated during the critical period for monocular deprivation. We found that chondroitinase ABC treatment coupled with reverse lid-suturing causes a complete recovery of ocular dominance, visual acuity, and dendritic spine density in adult rats. Thus, manipulations of the extracellular matrix can be used to promote functional recovery in the adult cortex.amblyopia ͉ chondroitin sulfate ͉ extracellular matrix ͉ glycosaminoglycan ͉ plasticity A n abnormal visual experience during development results in defective visual function. For instance, cataract or anisometropia in early childhood leads to a condition of reduced visual acuity (amblyopia) that can be fully recovered only if the treatment of these conditions is performed during early infancy (1). The lack of substantial recovery from amblyopia in the adult has been attributed to a decline in the plasticity of cortical circuits occurring during late postnatal development. Indeed, studies in animals have shown that monocular deprivation (MD) impairs visual cortical responses to the deprived eye and affects axonal morphology and dendritic spine density only if performed during a critical period of postnatal development (2-6). The ability to recover from the deficits induced by MD declines with age; reopening the previously deprived eye or reverse lidsuturing (RS) in young animals results in full recovery of ocular dominance, but these procedures become progressively less effective with age and are practically ineffective in the adult (7-9). Recovery from the amblyopic effect of MD is also progressively less efficient during development. In the adult, visual acuity shows small recoveries even if its final level continues to be pathologically low (10, 11). Similarly, a limited recovery of visual acuity can also be observed in adult amblyopic patients in particular conditions (1), although visual acuity remains largely abnormal.These observations suggest that the adult visual cortex expresses factors that inhibit experience-dependent plasticity and that develop in conjunction with the end of the critical period. The molecular identity of these factors is only partially known (12); studies performed in rodents have attributed the closure of the critical period to the maturation of inhibitory intracortical circuitry (13,14) and to developmental changes in the expression of molecular factors regulating synaptic plasticity (15, 16). Recently, it has been shown that at least part of the low level of plasticity of the adult visual cortex is due to the condensation of extracellular matrix molecules in perineuronal nets (PNNs). Indeed, chondr...

Extracellular matrix inhibits structural and functional plasticity of dendritic spines in the adult visual cortex

“…This unbalance of spine density, and of excitatory synaptic input, is maintained through the entire life span even if, in adulthood, the dominant eye is sutured (reverse suture) and therefore there is no recovery of function. However, if the reverse suture is paired with the ChABC treatment, functional amblyopia is partially reverted and spine density is rescued 12 . At the light of our results, we can envision that the recovery of connectivity between the amblyopic eye and the cortex occurs because of the potentiation of existing synapses and because of the formation of new spines.…”

“…On the day of surgery, animals were anesthetized with i.p. injection of avertin (0.2 ml per 10 g)/protease-free ChABC (40 U ml À 1 , Seikagaku) was diluted in sterile artificial cerebrospinal fluid (ACSF) 6,12 . A volume of 1 ml of solution per site at three sites anterior of the visual cortex was delivered at a depth of 500 mm.…”

“…The direct link with plasticity is stressed by the activity-regulated maturation of EM [5][6][7] ending in parallel with the closure of the juvenile critical period of heightened plasticity 6,8 . The relationship between critical period closure and EM is reciprocal, as alterations of the EM structure prolong the critical period 9,10 and plasticity processes can be partially restored in the adult brain by degradation of the EM [11][12][13][14][15] . Key components of the extracellular environment are the chondroitin sulfate proteoglycans (CSPGs): these molecules are formed by a proteic scaffold supporting chondroitin sulfate glycosaminoglycan chains.…”

“…CSPGs can be degraded by the action of the bacterial enzyme chondroitinase ABC (ChABC) that cleaves the side chains of CSPGs from the proteic core. The injection of ChABC in the visual cortex and in the amygdala has been shown to reactivate juvenile forms of experience-dependent plasticity in adult rodents 12,13 . Similarly, the injection of ChABC in the damaged rat spinal cord was also found to improve synaptic plasticity after spinal cord injury 20 .…”

Extracellular Matrix Plasticity and GABAergic Inhibition of Prefrontal Cortex Pyramidal Cells Facilitates Relapse to Heroin Seeking

“…In the last decade, the role of the ECM and more specifically the role of matrix molecules in perineuronal nets, both in neural development and synaptic plasticity, has attracted attention (Pizzorusso et al, 2002;Dityatev and Schachner, 2003). Studies on the role of the ECM in plasticity of the visual cortex (Pizzorusso et al, 2002(Pizzorusso et al, , 2006 and hippocampal-dependent learning (Meighan et al, 2006) gave way to the intriguing prospect that the ECM contributes to various forms of persistent neuroadaptation (Wright and Harding, 2009), including those resulting from repeated drug exposure. In support of this, a study by Brown et al (2007) suggests that alteration of ECM plasticity by inhibition of matrix metalloproteinase (MMP) activity reduces the conditioned rewarding effects of cocaine in a conditioned place preference model.…”