Synaptic Mechanisms of Activity-Dependent Remodeling in Visual Cortex during Monocular Deprivation

It has long been appreciated that in the visual cortex, particularly within a postnatal critical period for experience-dependent plasticity, the closure of one eye results in a shift in the responsiveness of cortical cells toward the experienced eye. While the functional aspects of this ocular dominance shift have been studied for many decades, their cortical substrates and synaptic mechanisms remain elusive. Nonetheless, it is becoming increasingly clear that ocular dominance plasticity is a complex phenomenon that appears to have an early and a late component. Early during monocular deprivation, deprived eye cortical synapses depress, while later during the deprivation open eye synapses potentiate. Here we review current literature on the cortical mechanisms of activity-dependent plasticity in the visual system during the critical period. These studies shed light on the role of activity in shaping neuronal structure and function in general and can lead to insights regarding how learning is acquired and maintained at the neuronal level during normal and pathological brain development.

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Critical period for monocular deprivation in the cat visual cortex

Journal of Neurophysiology ◽

10.1152/jn.1992.67.1.197 ◽

1992 ◽

Vol 67 (1) ◽

pp. 197-202 ◽

Cited By ~ 157

Author(s):

N. W. Daw ◽

K. Fox ◽

H. Sato ◽

D. Czepita

Keyword(s):

Visual Cortex ◽

Critical Period ◽

Single Cells ◽

Ocular Dominance ◽

Monocular Deprivation ◽

Significant Shift ◽

Cat Visual Cortex

1. Cats were monocularly deprived for 3 mo starting at 8-9 mo, 12 mo, 15 mo, and several years of age. Single cells were recorded in both visual cortexes of each cat, and the ocular dominance and layer determined for each cell. Ocular dominance histograms were then constructed for layers II/III, IV, and V/VI for each group of animals. 2. There was a statistically significant shift in the ocular dominance for cells in layers II/III and V/VI for the animals deprived between 8-9 and 11-12 mo of age. There was a small but not statistically significant shift for cells in layer IV from the animals deprived between 8-9 and 11-12 mo of age, and for cells in layers V/VI from the animals deprived between 15 and 18 mo of age. There was no noticeable shift in ocular dominance for any other layers in any other group of animals. 3. We conclude that the critical period for monocular deprivation is finally over at approximately 1 yr of age for extragranular layers (layers II, III, V, and VI) in visual cortex of the cat.

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Critical periods in amblyopia

Visual Neuroscience ◽

10.1017/s0952523817000219 ◽

2018 ◽

Vol 35 ◽

Cited By ~ 47

Author(s):

TAKAO K. HENSCH ◽

ELIZABETH M. QUINLAN

Keyword(s):

Visual Cortex ◽

Critical Period ◽

Molecular Mechanisms ◽

Ocular Dominance ◽

Molecular Genetic ◽

Monocular Deprivation ◽

Critical Periods ◽

Developmental Constraints ◽

Early Postnatal Development ◽

Visual Cortical

AbstractThe shift in ocular dominance (OD) of binocular neurons induced by monocular deprivation is the canonical model of synaptic plasticity confined to a postnatal critical period. Developmental constraints on this plasticity not only lend stability to the mature visual cortical circuitry but also impede the ability to recover from amblyopia beyond an early window. Advances with mouse models utilizing the power of molecular, genetic, and imaging tools are beginning to unravel the circuit, cellular, and molecular mechanisms controlling the onset and closure of the critical periods of plasticity in the primary visual cortex (V1). Emerging evidence suggests that mechanisms enabling plasticity in juveniles are not simply lost with age but rather that plasticity is actively constrained by the developmental up-regulation of molecular ‘brakes’. Lifting these brakes enhances plasticity in the adult visual cortex, and can be harnessed to promote recovery from amblyopia. The reactivation of plasticity by experimental manipulations has revised the idea that robust OD plasticity is limited to early postnatal development. Here, we discuss recent insights into the neurobiology of the initiation and termination of critical periods and how our increasingly mechanistic understanding of these processes can be leveraged toward improved clinical treatment of adult amblyopia.

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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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Postnatal development of functional properties of visual cortical cells in rats with excitotoxic lesions of basal forebrain cholinergic neurons

Visual Neuroscience ◽

10.1017/s0952523800008816 ◽

1997 ◽

Vol 14 (1) ◽

pp. 111-123 ◽

Cited By ~ 14

Author(s):

Rosita Siciliano ◽

Gigliola Fontanesi ◽

Fiorella Casamenti ◽

Nicoletta Berardi ◽

Paola Bagnoli ◽

...

Keyword(s):

Visual Cortex ◽

Postnatal Development ◽

Functional Properties ◽

Basal Forebrain ◽

Critical Period ◽

Ocular Dominance ◽

Cholinergic Neurons ◽

Field Size ◽

Cortical Cells ◽

Visual Cortical

AbstractIn the rat, visual cortical cells develop their functional properties during a period termed as critical period, which is included between eye opening, i.e.˘postnatal day (PD) 15, and PD40. The present investigation was aimed at studying the influence of cortical cholinergic afferents from the basal forebrain (BF) on the development of functional properties of visual cortical neurons. At PD15, rats were unilaterally deprived of the cholinergic input to the visual cortex by stereotaxic injections of quisqualic acid in BF cholinergic nuclei projecting to the visual cortex. Cortical cell functional properties, such as ocular dominance, orientation selectivity, receptive-field size, and cell responsiveness were then assessed by extracellular recordings in the visual cortex ipsilateral to the lesioned BF both during the critical period (PD30) and after its end (PD45). After the recording session, the rats were sacrificed and the extent of both cholinergic lesion in BF and cholinergic depletion in the visual cortex was determined. Our results show that lesion of BF cholinergic nuclei transiently alters the ocular dominance of visual cortical cells while it does not affect the other functional properties tested. In particular, in lesioned animals recorded during the critical period, a higher percentage of visual cortical cells was driven by the contralateral eye with respect to normal animals. After the end of the critical period, the ocular dominance distribution of animals with cholinergic deafferentation was not significantly different from that of controls. Our results suggest the possibility that lesions of BF cholinergic neurons performed during postnatal development only transiently interfere with cortical competitive processes.

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Lateral geniculate neurons show robust ocular dominance plasticity

10.1101/097923 ◽

2017 ◽

Author(s):

Juliane Jäpel ◽

Mark Hübener ◽

Tobias Bonhoeffer ◽

Tobias Rose

Keyword(s):

Visual Cortex ◽

Visual System ◽

Ocular Dominance ◽

Monocular Deprivation ◽

Ocular Dominance Plasticity ◽

Dependent Plasticity ◽

Two Photon ◽

Lateral Geniculate

AbstractExperience-dependent plasticity in the mature visual system is considered exclusively cortical. Using chronic two-photon Ca2+ imaging, we found evidence against this tenet: dLGN cells showed robust ocular dominance shifts after monocular deprivation. Most, but not all responses of dLGN cell boutons in binocular visual cortex were monocular during baseline. Following deprivation, however, deprived-eye dominated boutons became responsive to the non-deprived eye. Thus, plasticity of dLGN neurons contributes to cortical ocular dominance shifts.

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Arc restores juvenile plasticity in adult mouse visual cortex

10.1101/130880 ◽

2017 ◽

Author(s):

Kyle R. Jenks ◽

Taekeun Kim ◽

Elissa D. Pastuzyn ◽

Hiroyuki Okuno ◽

Andrew V. Taibi ◽

...

Keyword(s):

Visual Cortex ◽

Neural Plasticity ◽

Critical Period ◽

Adult Mouse ◽

Monocular Deprivation ◽

Protein Synthesis Inhibitor ◽

Adult Mice ◽

Mouse Visual Cortex ◽

Activity Dependent

AbstractThe molecular basis for the decline in experience-dependent neural plasticity over age remains poorly understood. In visual cortex, the robust plasticity induced in juvenile mice by brief monocular deprivation (MD) during the critical period is abrogated by genetic deletion of Arc, an activity-dependent regulator of excitatory synaptic modification. Here we report that augmenting Arc expression in adult mice prolongs juvenile-like plasticity in visual cortex, as assessed by recordings of ocular dominance (OD) plasticity in vivo. A distinguishing characteristic of juvenile OD plasticity is the weakening of deprived-eye responses, believed to be accounted for by the mechanisms of homosynaptic long-term depression (LTD). Accordingly, we also found increased LTD in visual cortex of adult mice with augmented Arc expression, and impaired LTD in visual cortex of juvenile mice that lack Arc or have been treated in vivo with a protein synthesis inhibitor. Further, we found that although activity-dependent expression of Arc mRNA does not change with age, expression of Arc protein is maximal during the critical period and declines in adulthood. Finally, we show that acute augmentation of Arc expression in wild type adult mouse visual cortex is sufficient to restore juvenile-like plasticity. Together, our findings suggest a unifying molecular explanation for the age- and activity-dependent modulation of synaptic sensitivity to deprivation.Significance StatementNeuronal plasticity peaks early in life during critical periods and normally declines with age, but the molecular changes that underlie this decline are not fully understood. Using the mouse visual cortex as a model, we found that activity-dependent expression of the neuronal protein Arc peaks early in life, and that loss of activity-dependent Arc expression parallels loss of synaptic plasticity in the visual cortex. Genetic overexpression of Arc prolongs the critical period of visual cortex plasticity and acute viral expression of Arc in adult mice can restore juvenile-like plasticity. These findings provide a mechanism for the loss of excitatory plasticity with age, and suggest that Arc may be an exciting therapeutic target for modulation of the malleability of neuronal circuits.

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Activation of somatostatin interneurons by nicotinic modulator Lypd6 enhances plasticity and functional recovery in the adult mouse visual cortex

10.1101/155465 ◽

2017 ◽

Cited By ~ 1

Author(s):

Masato Sadahiro ◽

Michael P. Demars ◽

Poromendro Burman ◽

Priscilla Yevoo ◽

Andreas Zimmer ◽

...

Keyword(s):

Visual Cortex ◽

Functional Recovery ◽

Critical Period ◽

Cortical Plasticity ◽

Monocular Deprivation ◽

Adult Brain ◽

Clinical Issue ◽

Dependent Plasticity ◽

Excitatory Neurons ◽

Interneuron Activity

AbstractThe limitation of plasticity in the adult brain impedes functional recovery later in life from brain injury or disease. This pressing clinical issue may be resolved by enhancing plasticity in the adult brain. One strategy for triggering robust plasticity in adulthood is to reproduce one of the hallmark physiological events of experience-dependent plasticity observed during the juvenile critical period – rapidly reduce the activity of parvalbumin (PV)-expressing interneurons and disinhibit local excitatory neurons. This may be achieved through enhancement of local inhibitory inputs, particularly those of somatostatin (SST)-expressing interneurons. However, to date the means for manipulating SST interneurons for enhancing cortical plasticity in the adult brain are not known. We show that SST interneuron-selective overexpression of Lypd6, an endogenous nicotinic signaling modulator, enhances ocular dominance plasticity in the adult primary visual cortex (V1). Lypd6 overexpression mediates a rapid experience-dependent increase in the visually evoked activity of SST interneurons as well as a simultaneous reduction in PV interneuron activity and disinhibition of excitatory neurons. Recapitulating this transient activation of SST interneurons using chemogenetics similarly enhanced V1 plasticity. Notably, we show that SST-selective Lypd6 overexpression restores visual acuity in amblyopic mice that underwent early long-term monocular deprivation. Our data in both male and female mice reveal selective modulation of SST interneurons and a putative downstream circuit mechanism as an effective method for enhancing experience-dependent cortical plasticity as well as functional recovery in adulthood.Significance StatementThe decline of cortical plasticity after closure of juvenile critical period consolidates neural circuits and behavior, but this limits functional recovery from brain diseases and dysfunctions in later life. Here we show that activation of cortical SST interneurons by Lypd6, an endogenous modulator of nicotinic acetylcholine receptors (nAChRs), enhances experience-dependent plasticity and recovery from amblyopia in adulthood. This manipulation triggers rapid reduction of PV interneuron activity and disinhibition of excitatory neurons, which are known hallmarks of cortical plasticity during juvenile critical periods. Our study demonstrates modulation of SST interneurons by Lypd6 to achieve robust levels of cortical plasticity in the adult brain and may provide promising targets for restoring brain function in the event of brain trauma or disease.

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Light reintroduction after dark exposure reactivates plasticity in adults via perisynaptic activation of MMP-9

eLife ◽

10.7554/elife.27345 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 23

Author(s):

Sachiko Murase ◽

Crystal L Lantz ◽

Elizabeth M Quinlan

Keyword(s):

Critical Period ◽

Adult Mouse ◽

Ocular Dominance ◽

Visual Deprivation ◽

Monocular Deprivation ◽

Genetic Ablation ◽

Dark Exposure ◽

Cortical Synapses ◽

Mouse Visual Cortex ◽

Metalloproteinase 9

The sensitivity of ocular dominance to regulation by monocular deprivation is the canonical model of plasticity confined to a critical period. However, we have previously shown that visual deprivation through dark exposure (DE) reactivates critical period plasticity in adults. Previous work assumed that the elimination of visual input was sufficient to enhance plasticity in the adult mouse visual cortex. In contrast, here we show that light reintroduction (LRx) after DE is responsible for the reactivation of plasticity. LRx triggers degradation of the ECM, which is blocked by pharmacological inhibition or genetic ablation of matrix metalloproteinase-9 (MMP-9). LRx induces an increase in MMP-9 activity that is perisynaptic and enriched at thalamo-cortical synapses. The reactivation of plasticity by LRx is absent in Mmp9−/− mice, and is rescued by hyaluronidase, an enzyme that degrades core ECM components. Thus, the LRx-induced increase in MMP-9 removes constraints on structural and functional plasticity in the mature cortex.

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Axonal processes and neural plasticity. III. Competition for dendrites

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.1997.0183 ◽

1997 ◽

Vol 352 (1364) ◽

pp. 1975-1983 ◽

Cited By ~ 2

Author(s):

T. Elliott ◽

C. I. Howarth ◽

N. R. Shadbolt

Keyword(s):

Neural Plasticity ◽

Critical Period ◽

Ocular Dominance ◽

Dendritic Morphology ◽

Monocular Deprivation ◽

Topographic Map ◽

Cortical Cells ◽

Optic Nerve Stimulation ◽

Axonal Process ◽

Dendritic Fields

In previous work we have developed a computational framework for topographic map formation and plasticity based on axonal process sprouting and retraction, in which sprouting and retraction are governed by competition for neurotrophic support. Here we show that such an approach can account for certain aspects of the dendritic morphology of cortical maps. In particular, we model the development of ocular dominance columns in the primary visual cortex and show that cortical cells near to column boundaries prefer to elaborate dendritic fields which avoid crossing the boundaries. This emerges as different functional inputs are spatially separated. We predict that afferent segregation occurs before or simultaneously with, but not after, the emergence of dendritic bias. We predict that animals reared with complete but asynchronous stimulation of the optic nerves do not develop a dendritic bias. We suggest that the emergence of a dendritic bias might provide a partial account for the critical period for a response to monocular deprivation. In particular, we predict that animals reared with asynchronous optic nerve stimulation might exhibit an extended critical period. Our results also indicate that the number of synapses supported by cortical cells depends on the intra–ocular image correlations used in our simulations. This suggests that inter–ocular image correlations, and thus strabismic rearing of kittens, may also affect the innervation density.

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Role of visual experience in activating critical period in cat visual cortex

Journal of Neurophysiology ◽

10.1152/jn.1985.53.2.572 ◽

1985 ◽

Vol 53 (2) ◽

pp. 572-589 ◽

Cited By ~ 33

Author(s):

G. D. Mower ◽

W. G. Christen

Keyword(s):

Visual Cortex ◽

Visual Experience ◽

Ocular Dominance ◽

Orientation Selectivity ◽

Monocular Deprivation ◽

Total Darkness ◽

Cortical Cells ◽

Visual Cortical ◽

Dark Rearing ◽

Made In

Cats were reared in total darkness from birth until 4-5 mo of age (DR cats, n = 7) or with very brief visual experience (1 or 2 days) during an otherwise similar period of dark rearing [DR(1) cats, n = 3; DR(2) cats, n = 7]. Single-cell recordings were made in area 17 of visual cortex at the end of this rearing period and/or after a subsequent prolonged period of monocular deprivation. Control observations were made in normal cats (n = 3), cats reared with monocular deprivation from birth (n = 4), and cats monocularly deprived after being reared normally until 4 mo of age (n = 2). After rearing cats in total darkness, the majority of visual cortical cells were binocularly driven and the overall distribution of ocular dominance was not different from that of normal cats. Orientation-selective cells were very rare in dark-reared cats. Monocular deprivation imposed after dark rearing resulted in selective development of connections from the open eye. Most cells were responsive only to the open eye and the majority of these were orientation selective. These results were similar to, though less severe than, those found in cats reared with monocular deprivation from birth. Monocular deprivation imposed after 4 mo of normal rearing did not produce selective development of connections from the open eye in terms of either ocular dominance or orientation selectivity. In DR(1) cats visual cortical physiology was degraded in comparison to dark-reared cats after the rearing period. Most cells were binocularly driven but there was a higher frequency of unresponsive cells and a reduced frequency of orientation-selective cells. Subsequent monocular deprivation resulted in a further decrease in the number of binocularly driven cells and an increase in unresponsive cells. However, it did not produce a bias in favor of the open eye in terms of either ocular dominance or orientation selectivity. In DR(2) cats there was a high incidence of unresponsive cells and a marked loss of binocularly driven cells after the rearing period. Subsequent monocular deprivation failed to produce any significant changes.(ABSTRACT TRUNCATED AT 400 WORDS)

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