Non-cell autonomous OTX2 homeoprotein regulates visual cortex plasticity through Gadd45

AbstractThe non-cell autonomous transfer of OTX2 homeoprotein transcription factor into juvenile mouse cerebral cortex regulates parvalbumin interneuron maturation and critical period timing. By analyzing gene expression in primary visual cortex of wild-type and Otx2+/GFP mice at plastic and non-plastic ages, we identified several putative genes implicated in Otx2-dependent visual cortex plasticity for ocular dominance. Cortical OTX2 infusion in juvenile mice induced Gadd45b/g expression through direct regulation of transcription. Intriguingly, a reverse effect was found in the adult, where reducing cortical OTX2 resulted in Gadd45b/g up-regulation. Viral expression of Gadd45b in adult visual cortex directly induced ocular dominance plasticity with concomitant changes in MeCP2 foci within parvalbumin interneurons and in methylation states of several plasticity gene promoters, suggesting epigenetic regulation. This interaction provides a molecular mechanism for OTX2 to trigger critical period plasticity yet suppress adult plasticity.

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Orientation Selectivity Is Reduced by Monocular Deprivation in Combination With PKA Inhibitors

Journal of Neurophysiology ◽

10.1152/jn.2002.88.4.1933 ◽

2002 ◽

Vol 88 (4) ◽

pp. 1933-1940 ◽

Cited By ~ 6

Author(s):

Chris J. Beaver ◽

Quentin S. Fischer ◽

Qinghua Ji ◽

Nigel W. Daw

Keyword(s):

Visual Cortex ◽

Protein Kinase ◽

Critical Period ◽

Ocular Dominance ◽

Receptive Fields ◽

Direction Selectivity ◽

Orientation Selectivity ◽

Monocular Deprivation ◽

Ocular Dominance Plasticity ◽

Kinase A

We have previously shown that the protein kinase A (PKA) inhibitor, 8-chloroadenosine-3′,5′–monophosphorothioate (Rp-8-Cl-cAMPS), abolishes ocular dominance plasticity in the cat visual cortex. Here we investigate the effect of this inhibitor on orientation selectivity. The inhibitor reduces orientation selectivity in monocularly deprived animals but not in normal animals. In other words, PKA inhibitors by themselves do not affect orientation selectivity, nor does monocular deprivation by itself, but monocular deprivation in combination with a PKA inhibitor does affect orientation selectivity. This result is found for the receptive fields in both deprived and nondeprived eyes. Although there is a tendency for the orientation selectivity in the nondeprived eye to be higher than the orientation selectivity in the deprived eye, the orientation selectivity in both eyes is considerably less than normal. The result is striking in animals at 4 wk of age. The effect of the monocular deprivation on orientation selectivity is reduced at 6 wk of age and absent at 9 wk of age, while the effect on ocular dominance shifts is less changed in agreement with previous results showing that the critical period for orientation/direction selectivity ends earlier than the critical period for ocular dominance. We conclude that closure of one eye in combination with inhibition of PKA reduces orientation selectivity during the period that orientation selectivity is still mutable and that the reduction in orientation selectivity is transferred to the nondeprived eye.

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Progressive maturation of silent synapses governs the duration of a critical period

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1506488112 ◽

2015 ◽

Vol 112 (24) ◽

pp. E3131-E3140 ◽

Cited By ~ 50

Author(s):

Xiaojie Huang ◽

Sophia K. Stodieck ◽

Bianka Goetze ◽

Lei Cui ◽

Man Ho Wong ◽

...

Keyword(s):

Visual Cortex ◽

Critical Period ◽

Neural Circuit ◽

Ocular Dominance ◽

Critical Periods ◽

Ocular Dominance Plasticity ◽

Silent Synapses ◽

Synapse Maturation ◽

Silent Synapse ◽

Visual Cortical

During critical periods, all cortical neural circuits are refined to optimize their functional properties. The prevailing notion is that the balance between excitation and inhibition determines the onset and closure of critical periods. In contrast, we show that maturation of silent glutamatergic synapses onto principal neurons was sufficient to govern the duration of the critical period for ocular dominance plasticity in the visual cortex of mice. Specifically, postsynaptic density protein-95 (PSD-95) was absolutely required for experience-dependent maturation of silent synapses, and its absence before the onset of critical periods resulted in lifelong juvenile ocular dominance plasticity. Loss of PSD-95 in the visual cortex after the closure of the critical period reinstated silent synapses, resulting in reopening of juvenile-like ocular dominance plasticity. Additionally, silent synapse-based ocular dominance plasticity was largely independent of the inhibitory tone, whose developmental maturation was independent of PSD-95. Moreover, glutamatergic synaptic transmission onto parvalbumin-positive interneurons was unaltered in PSD-95 KO mice. These findings reveal not only that PSD-95–dependent silent synapse maturation in visual cortical principal neurons terminates the critical period for ocular dominance plasticity but also indicate that, in general, once silent synapses are consolidated in any neural circuit, initial experience-dependent functional optimization and critical periods end.

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Enhanced NR2A Subunit Expression and Decreased NMDA Receptor Decay Time at the Onset of Ocular Dominance Plasticity in the Ferret

Journal of Neurophysiology ◽

10.1152/jn.1999.81.5.2587 ◽

1999 ◽

Vol 81 (5) ◽

pp. 2587-2591 ◽

Cited By ~ 106

Author(s):

Elizabeth B. Roberts ◽

Ary S. Ramoa

Keyword(s):

Visual Cortex ◽

Nmda Receptor ◽

Functional Properties ◽

Decay Time ◽

Critical Period ◽

Ocular Dominance ◽

Ocular Dominance Plasticity ◽

Abrupt Decrease ◽

Subunit Expression ◽

Nr2a Subunit

Enhanced NR2A subunit expression and decreased NMDA receptor decay time at the onset of ocular dominance plasticity in the ferret. The NMDA subtype of glutamate receptor is known to exhibit marked changes in subunit composition and functional properties during neural development. The prevailing idea is that NMDA receptor–mediated synaptic responses decrease in duration after the peak of cortical plasticity in rodents. Accordingly, it is believed that shortening of the NMDA receptor–mediated current underlies the developmental reduction of ocular dominance plasticity. However, some previous evidence actually suggests that the duration of NMDA receptor currents decreases before the peak of plasticity. In the present study, we have examined the time course of NMDA receptor changes and how they correlate with the critical period of ocular dominance plasticity in the visual cortex of a highly binocular animal, the ferret. The expression of NMDA receptor subunits NR1, NR2A, and NR2B was examined in animals ranging in age from postnatal day 16 to adult using Western blotting. Functional properties of NMDA receptors in layer IV cortical neurons were studied using whole cell patch-clamp techniques in an in vitro slice preparation of ferret primary visual cortex. We observed a remarkable increase in NR1 and NR2A, but not NR2B, expression after eye opening. The NMDA receptor–mediated synaptic currents showed an abrupt decrease in decay time concurrent with the increase in NR2A subunit expression. Importantly, these changes occurred in parallel with increased ocular dominance plasticity reported in the ferret. In conclusion, molecular changes leading to decreased duration of the NMDA receptor excitatory postsynaptic current may be a requirement for the onset, rather than the end, of the critical period of ocular dominance plasticity.

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The Critical Period for Ocular Dominance Plasticity in the Ferret’s Visual Cortex

Journal of Neuroscience ◽

10.1523/jneurosci.19-16-06965.1999 ◽

1999 ◽

Vol 19 (16) ◽

pp. 6965-6978 ◽

Cited By ~ 145

Author(s):

Naoum P. Issa ◽

Joshua T. Trachtenberg ◽

Barbara Chapman ◽

Kathleen R. Zahs ◽

Michael P. Stryker

Keyword(s):

Visual Cortex ◽

Critical Period ◽

Ocular Dominance ◽

Ocular Dominance Plasticity

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Layer differences in the effect of monocular vision in light- and dark-reared kittens

Visual Neuroscience ◽

10.1017/s0952523801185147 ◽

2001 ◽

Vol 18 (5) ◽

pp. 811-820 ◽

Cited By ~ 20

Author(s):

CHRISTOPHER J. BEAVER ◽

QINGHUA JI ◽

NIGEL W. DAW

Keyword(s):

Visual Cortex ◽

Critical Period ◽

Ocular Dominance ◽

Large Change ◽

Monocular Deprivation ◽

Monocular Vision ◽

Ocular Dominance Plasticity ◽

The Difference ◽

Dark Rearing

We compared the effect of 2 days of monocular vision on the ocular dominance of cells in the visual cortex of light-reared kittens with the effect in dark-reared kittens at 6, 9, and 14 weeks of age, and analyzed the results by layer. The size of the ocular-dominance shift declined with age in all layers in light-reared animals. There was not a large change in the ocular-dominance shift with age in dark-reared animals in any layer, suggesting that dark rearing largely keeps the cortex in the immature 6-week state until 14 weeks or longer, although there was a slight decrease in layers II, III, and IV, and a slight increase in layers V and VI. At 14 weeks, the difference between light- and dark-reared animals was smallest in layer IV, larger in layers II/III, and largest in layers V/VI, suggesting that dark rearing has a large effect on intracortical synapses and a small effect on geniculocortical synapses. There was a significant ocular-dominance shift in layer IV at 14 weeks of age in both light- animals and dark-reared animals, showing that the critical period for ocular-dominance plasticity is not ended at this age. While the ocular-dominance shift after 26 h of monocular deprivation in 6-week animals was similar in light- and dark-reared animals, after 14 h it was smaller in dark-reared animals, showing that ocular-dominance changes occur more slowly in dark-reared animals at this age, in agreement with Mower (1991). Increases in selectivity for axis of movement after 26 h of monocular vision were seen in dark-reared animals at 6 weeks of age, but not at 9 or 14 weeks of age, showing that the critical period for axial selectivity ends earlier than the critical period for ocular dominance in dark-reared animals, as it does in light-reared animals.

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Enhancement of visual cortex plasticity by dark exposure

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2016.0159 ◽

2017 ◽

Vol 372 (1715) ◽

pp. 20160159 ◽

Cited By ~ 13

Author(s):

Irina Erchova ◽

Asta Vasalauskaite ◽

Valentina Longo ◽

Frank Sengpiel

Keyword(s):

Visual Cortex ◽

Critical Period ◽

Time Course ◽

Ocular Dominance ◽

Monocular Deprivation ◽

Homeostatic Plasticity ◽

Ocular Dominance Plasticity ◽

Intrinsic Signals ◽

Significant Difference ◽

Dark Exposure

Dark rearing is known to delay the time course of the critical period for ocular dominance plasticity in the visual cortex. Recent evidence suggests that a period of dark exposure (DE) may enhance or reinstate plasticity even after closure of the critical period, mediated through modification of the excitatory–inhibitory balance and/or removal of structural brakes on plasticity. Here, we investigated the effects of a week of DE on the recovery from a month of monocular deprivation (MD) in the primary visual cortex (V1) of juvenile mice. Optical imaging of intrinsic signals revealed that ocular dominance in V1 of mice that had received DE recovered slightly more quickly than of mice that had not, but the level of recovery after three weeks was similar in both groups. Two-photon calcium imaging showed no significant difference in the recovery of orientation selectivity of excitatory neurons between the two groups. Parvalbumin-positive (PV+) interneurons exhibited a smaller ocular dominance shift during MD but again no differences in subsequent recovery. The percentage of PV+ cells surrounded by perineuronal nets, a structural brake on plasticity, was lower in mice with than those without DE. Overall, DE causes a modest enhancement of mouse visual cortex plasticity. This article is part of the themed issue ‘Integrating Hebbian and homeostatic plasticity’.

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GAP-43 in the cat visual cortex during postnatal development

Visual Neuroscience ◽

10.1017/s0952523800005782 ◽

1990 ◽

Vol 4 (6) ◽

pp. 585-593 ◽

Cited By ~ 19

Author(s):

Helen McIntosh ◽

Nigel Daw ◽

David Parkinson

Keyword(s):

Visual Cortex ◽

Postnatal Development ◽

Critical Period ◽

Primary Motor Cortex ◽

Ocular Dominance ◽

Monocular Deprivation ◽

Ocular Dominance Plasticity ◽

Cat Visual Cortex ◽

Age Gap ◽

Slow Decline

AbstractGAP-43 levels have been determined by immunoassay in cat visual cortex during postnatal development to test the idea that GAP-43 expression could be related to the duration of the critical period for plasticity. For comparison, GAP-43 levels have also been assayed in primary motor cortex, primary somatosensory cortex, and cerebellum at each age. GAP-43 levels were high in all regions at 5 d (with concentrations ranging from 7−10 ng;/μg protein) and then declined 60−80% by 60 d of age. After 60 d of age, GAP-43 concentrations in each region continued a slow decline to adult values, which ranged from 0.5−2 ng/μg protein. To test for the involvement of GAP-43 in ocular dominance plasticity during the critical period, the effect of visual deprivation on GAP-43 levels was investigated. Monocular deprivation for 2−7 d, ending at either 27 or 35 d of age, had no effect on total membrane levels of GAP-43. The concentrations of membrane-associated GAP-43 prior to 40 d of age correlate with events that occur during postnatal development of the cat visual cortex. However, the slow decline in membrane-associated GAP-43 levels after 40 d of age may be an index of relative plasticity remaining after the peak of the critical period.

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Faculty Opinions recommendation of PirB restricts ocular-dominance plasticity in visual cortex.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1040077.488994 ◽

2006 ◽

Author(s):

Lutz Walter

Keyword(s):

Visual Cortex ◽

Ocular Dominance ◽

Ocular Dominance Plasticity

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Critical periods for functional and anatomical compensation in lateral suprasylvian visual area following removal of visual cortex in cats

Journal of Neurophysiology ◽

10.1152/jn.1984.52.5.941 ◽

1984 ◽

Vol 52 (5) ◽

pp. 941-960 ◽

Cited By ~ 39

Author(s):

L. Tong ◽

R. E. Kalil ◽

P. D. Spear

Keyword(s):

Visual Cortex ◽

Critical Period ◽

Ocular Dominance ◽

Direction Selectivity ◽

Visual Area ◽

Critical Periods ◽

Cortex Lesion ◽

Thalamic Projections ◽

Adult Cats ◽

Visual Cortical

Previous experiments have found that neurons in the cat's lateral suprasylvian (LS) visual area of cortex show functional compensation following removal of visual cortical areas 17, 18, and 19 on the day of birth. Correspondingly, an enhanced retino-thalamic pathway to LS cortex develops in these cats. The present experiments investigated the critical periods for these changes. Unilateral lesions of areas 17, 18, and 19 were made in cats ranging in age from 1 day postnatal to 26 wk. When the cats were adult, single-cell recordings were made from LS cortex ipsilateral to the lesion. In addition, transneuronal autoradiographic methods were used to trace the retino-thalamic projections to LS cortex in many of the same animals. Following lesions in 18- and 26-wk-old cats, there is a marked reduction in direction-selective LS cortex cells and an increase in cells that respond best to stationary flashing stimuli. These results are similar to those following visual cortex lesions in adult cats. In contrast, the percentages of cells with these properties are normal following lesions made from 1 day to 12 wk of age. Thus the critical period for development of direction selectivity and greater responses to moving than to stationary flashing stimuli in LS cortex following a visual cortex lesion ends between 12 and 18 wk of age. Following lesions in 26-wk-old cats, there is a decrease in the percentage of cells that respond to the ipsilateral eye, which is similar to results following visual cortex lesions in adult cats. However, ocular dominance is normal following lesions made from 1 day to 18 wk of age. Thus the critical period for development of responses to the ipsilateral eye following a lesion ends between 18 and 26 wk of age. Following visual cortex lesions in 2-, 4-, or 8-wk-old cats, about 30% of the LS cortex cells display orientation selectivity to elongated slits of light. In contrast, few or no cells display this property in normal adult cats, cats with lesions made on the day of birth, or cats with lesions made at 12 wk of age or later. Thus an anomalous property develops for many LS cells, and the critical period for this property begins later (between 1 day and 2 wk) and ends earlier (between 8 and 12 wk) than those for other properties.(ABSTRACT TRUNCATED AT 400 WORDS)

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