It is well established that sensory cortices of animals can be modified by sensory experience, especially during a brief early critical period in development. Theoretical analyses indicate that there are two synaptic plasticity mechanisms required: input-specific synaptic modifications and global homeostatic mechanisms to provide stability to neural networks. Experience-dependent homeostatic synaptic plasticity mechanisms have subsequently been demonstrated in the visual cortex of juvenile animals. Here, we report that experiencedependent homeostatic synaptic plasticity persists through adulthood in the superficial layers of the mouse visual cortex. We found that 2 d of visual deprivation in the form of dark rearing is necessary and sufficient to cause an increase in AMPA receptor-mediated miniature EPSC amplitude in layer 2/3 neurons. This increase was rapidly reversed by 1 d of light exposure. This reversible change in synaptic strength persisted in adult mice past the critical period for ocular dominance plasticity, which is reported to end at ϳ1 month of age in rodents. Interestingly, the mechanism of homeostatic synaptic modifications in 3-month-old mice differed from that in young mice (3 weeks old) in that the multiplicative nature of synaptic scaling is lost. Our results demonstrate that the superficial layers of adult mouse visual cortex retain the ability to undergo reversible experience-dependent homeostatic synaptic plasticity.

Lack of a sensory input not only alters the cortical circuitry subserving the deprived sense, but also produces compensatory changes in the functionality of other sensory modalities. Here we report that visual deprivation produces opposite changes in synaptic function in primary visual and somatosensory cortices in rats, which are rapidly reversed by visual experience. This type of bidirectional cross-modal plasticity is associated with changes in synaptic AMPA receptor subunit composition.Loss of vision is usually accompanied by the increased functionality of other sensory modalities 1,2 . Systems-level analyses of cross-modal plasticity have revealed anatomical and functional rewiring of cortical circuits 3 . However, little is known about the cellular and molecular mechanisms underlying this type of plasticity. Here we examined whether manipulation of visual experience can induce bidirectional cross-modal plasticity of synaptic function in primary sensory cortices, and investigated the molecular mechanisms underlying this form of plasticity.To study cross-modal changes in synaptic function by visual deprivation, we dark-reared 4-week-old Long-Evans rats for a period of 1 week and then measured AMPA receptor (AMPAR)-mediated miniature excitatory postsynaptic currents (mEPSCs) in layer 2/3 pyramidal neurons in slices from primary visual, somatosensory and auditory cortex (Supplementary Methods online). In visual cortex, dark rearing produced an increase in mESPC amplitude that was reversed by re-exposing the rats to lighted conditions for 2 d Correspondence should be addressed to H.-K.L. (hlee21@umd.edu). 4 Current address: Brain Science Institute, Riken, Wako City, Saitama, Japan. 5 These authors contributed equally to this work.Note: Supplementary information is available on the Nature Neuroscience website. AUTHOR CONTRIBUTIONSA.G. and B.J. conducted the electrophysiology experiments (mEPSC recordings and rectification measurements, respectively) and assisted in writing the manuscript; L.W.X. and L.S. performed the biochemistry experiments; A.K. oversaw the electrophysiology (rectification measurements), contributed to discussions on experimental designs and collaborated on manuscript writing; H.-K.L. designed the studies, oversaw experiments, contributed to the electrophysiology (mEPSC recordings) and biochemistry and wrote the manuscript. COMPETING INTERESTS STATEMENTThe authors declare that they have no competing financial interests. (normal-reared (NR): 10.7 ± 0.6 pA, n = 8; dark-reared (DR): 12.4 ± 0.4 pA, n = 16; re-exposure to light (L): 10.7 ± 0.4 pA, n = 13; analysis of variance (ANOVA): F 2,34 = 5.968, P < 0.01; Fig. 1a). Notably, we observed the opposite changes in somatosensory cortex, where 1 week of dark rearing decreased the amplitude of mEPSCs and 2 d of light exposure reversed this effect (NR: 13.8 ± 0.8 pA, n = 12; DR: 11.3 ± 0.7 pA, n = 16; L: 14.1 ± 0.9 pA, n = 16; ANOVA: F 2,40 = 3.830, P < 0.04; Fig. 1b). Changes in synaptic transmission by dark rearing seems to be general for pr...

Learning ultimately relies on changes in the flow of activity within neural microcircuits. Plasticity of neural dynamics is particularly relevant for the processing of temporal information. Chronic stimulation of cultured rat cortical networks revealed ‘experience-dependent’ plasticity in neural dynamics. We observed changes in the temporal structure of activity that reflected the intervals used during training, suggesting that cortical circuits are inherently capable of temporal processing on short time scales.

Proper functioning of the visual system depends on maturation of both excitatory and inhibitory synapses within the visual cortex. Considering that perisomatic inhibition is one of the key factors that control the critical period in visual cortex, it is pertinent to understand its regulation by visual experience. To do this, we developed an immunohistochemical method that allows three-dimensional (3D) analysis of the glutamic acid decarboxylase (GAD) 65-positive inhibitory terminals in the visual cortex. Using this method on transgenic mice expressing yellow fluorescence protein (YFP) in a subset of neurons, we found that the number of somatic GAD65-puncta on individual layer 2/3 pyramidal neurons is reduced when mice are dark-reared from birth and reverted to normal levels by re-exposure to light. There was no change in GAD65-puncta volume or intensity. These results support the reorganization of inhibitory circuitry within layer 2/3 of visual cortex in response to changes in visual experience.