Neuronal circuits in the brain are shaped by experience during 'critical periods' in early postnatal life. In the primary visual cortex, this activity-dependent development is triggered by the functional maturation of local inhibitory connections and driven by a specific, late-developing subset of interneurons. Ultimately, the structural consolidation of competing sensory inputs is mediated by a proteolytic reorganization of the extracellular matrix that occurs only during the critical period. The reactivation of this process, and subsequent recovery of function in conditions such as amblyopia, can now be studied with realistic circuit models that might generalize across systems.

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Critical period plasticity in local cortical circuits.

The many faces of CREB

Monocular deprivation normally alters ocular dominance in the visual cortex only during a postnatal critical period (20 to 32 days postnatal in mice). We find that mutations in the Nogo-66 receptor (NgR) affect cessation of ocular dominance plasticity. In NgR-/- mice, plasticity during the critical period is normal, but it continues abnormally such that ocular dominance at 45 or 120 days postnatal is subject to the same plasticity as at juvenile ages. Thus, physiological NgR signaling from myelin-derived Nogo, MAG, and OMgp consolidates the neural circuitry established during experience-dependent plasticity. After pathological trauma, similar NgR signaling limits functional recovery and axonal regeneration.

/pdf/experience-driven-plasticity-of-visual-cortex-limited-by-320hdrlofw.pdf

Experience-driven plasticity of visual cortex limited by myelin and Nogo receptor.

Tumor Necrosis Factor-α Mediates One Component of Competitive, Experience-Dependent Plasticity in Developing Visual Cortex

In many regions of the developing brain, neuronal circuits undergo defined phases of enhanced plasticity, termed critical periods. Work in the rodent visual cortex has led to important insights into the cellular and molecular mechanisms regulating the timing of the critical period. Although there is little doubt that the maturation of specific inhibitory circuits plays a key role in the opening of the critical period in the visual cortex, it is less clear what puts an end to it. In this review, we describe the established mechanisms and point out where more experimental work is needed. We also show that plasticity in the visual cortex is present well before, and long after, the peak of the critical period.

Critical-Period Plasticity in the Visual Cortex

The adult cerebral cortex can adapt to environmental change. Using monocular deprivation as a paradigm, we find that rapid experience-dependent plasticity exists even in the mature primary visual cortex. However, adult cortical plasticity differs from developmental plasticity in two important ways. First, the effect of adult, but not juvenile monocular deprivation is strongly suppressed by administration of barbiturate just prior to recording visual evoked potentials, suggesting that the effect of adult experience can be inactivated acutely. Second, the effect of deprivation is less persistent over time in adults than in juveniles. This correlates with the known decline in CREB function during maturation of the visual cortex. To compensate for this decline in CREB function, we expressed persistently active VP16-CREB and find that it causes adult plasticity to become persistent. These results suggest that in development and adulthood, the regulation of a trans-synaptic signaling pathway controls the adaptive potential of cortical circuits.

/pdf/a-semi-persistent-adult-ocular-dominance-plasticity-in-c88nq3va96.pdf

Sarah J. Graham

Papers

A semi-persistent adult ocular dominance plasticity in visual cortex is stabilized by activated CREB.