Arc restores juvenile plasticity in adult mouse visual cortex

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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Arc restores juvenile plasticity in adult mouse visual cortex

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1700866114 ◽

2017 ◽

Vol 114 (34) ◽

pp. 9182-9187 ◽

Cited By ~ 19

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

The 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 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.

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Temporal patterns of fluoxetine-induced plasticity in the mouse visual cortex

10.1101/487553 ◽

2018 ◽

Author(s):

Anna Steinzeig ◽

Cecilia Cannarozzo ◽

Eero Castren

Keyword(s):

Visual Cortex ◽

Critical Period ◽

Ocular Dominance ◽

Temporal Patterns ◽

Monocular Deprivation ◽

Adult Brain ◽

Postnatal Life ◽

Critical Periods ◽

Mouse Visual Cortex

Heightened neuronal plasticity expressed during early postnatal life has been thought to permanently decline once critical periods have ended. For example, monocular deprivation is able to shift ocular dominance in the mouse visual cortex during the first months of life, but this effect is lost later in life. However, various treatments such as the antidepressant fluoxetine can reactivate a critical period-like plasticity in the adult brain. When monocular deprivation is supplemented with chronic fluoxetine administration, a major shift in ocular dominance is produced after the critical period has ended. In the current study, we characterized the temporal patterns of fluoxetine-induced plasticity in the adult mouse visual cortex, using in vivo optical imaging. We found that artificially-induced plasticity in ocular dominance extended beyond the duration of the naturally occurring critical period, and continued as long as fluoxetine was administered. However, this fluoxetine-induced plasticity period ended as soon as the drug was not given. Taken together, our data highlights how a combination of pharmacological treatment and environmental change could be used to improve strategies in antidepressant therapy in humans.

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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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Regulation of perineuronal nets in the adult cortex by the electrical activity of parvalbumin interneurons

10.1101/671719 ◽

2019 ◽

Cited By ~ 2

Author(s):

Gabrielle Devienne ◽

Sandrine Picaud ◽

Ivan Cohen ◽

Juliette Piquet ◽

Ludovic Tricoire ◽

...

Keyword(s):

Adult Mouse ◽

High Plasticity ◽

Critical Periods ◽

Cortical Circuits ◽

Perineuronal Net ◽

Parvalbumin Interneurons ◽

Mouse Visual Cortex ◽

Activity Dependent ◽

Dependent Mechanism

ABSTRACTPerineuronal net (PNN) accumulation around parvalbumin-expressing (PV) inhibitory interneurons marks the closure of critical periods of high plasticity, whereas PNN removal reinstates juvenile plasticity in the adult cortex. Using targeted chemogenetic in vivo approaches in the adult mouse visual cortex, we found that transient electrical silencing of PV interneurons, directly or through inhibition of local excitatory neurons, induced PNN regression. Conversely, excitation of either neuron types did not reduce the PNN. We also observed that chemogenetically inhibited PV interneurons exhibited reduced PNN compared to their untransduced neighbors, and confirmed that single PV interneurons express multiple genes enabling cell-autonomous control of their own PNN density. Our results indicate that PNNs are dynamically regulated in the adult by PV neurons acting as sensors of their local microcircuit activities. PNN regulation provides individual PV neurons with an activity-dependent mechanism to control the local remodeling of adult cortical circuits.

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

Journal of Experimental Neuroscience ◽

10.4137/jen.s2559 ◽

2009 ◽

Vol 2 ◽

pp. JEN.S2559 ◽

Cited By ~ 4

Author(s):

Cynthia D. Rittenhouse ◽

Ania K Majewska

Keyword(s):

Visual Cortex ◽

Critical Period ◽

Ocular Dominance ◽

Monocular Deprivation ◽

Neuronal Structure ◽

Cortical Cells ◽

Dependent Plasticity ◽

Cortical Synapses ◽

Activity Dependent ◽

Synaptic Mechanisms

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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Traumatic brain injury to primary visual cortex produces long-lasting circuit dysfunction

Communications Biology ◽

10.1038/s42003-021-02808-5 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Jan C. Frankowski ◽

Andrzej T. Foik ◽

Alexa Tierno ◽

Jiana R. Machhor ◽

David C. Lyon ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Visual Cortex ◽

Brain Injury ◽

Primary Visual Cortex ◽

Visual Stimuli ◽

Orientation Tuning ◽

V1 Neurons ◽

Adult Mice ◽

Electrophysiological Recordings

AbstractPrimary sensory areas of the mammalian neocortex have a remarkable degree of plasticity, allowing neural circuits to adapt to dynamic environments. However, little is known about the effects of traumatic brain injury on visual circuit function. Here we used anatomy and in vivo electrophysiological recordings in adult mice to quantify neuron responses to visual stimuli two weeks and three months after mild controlled cortical impact injury to primary visual cortex (V1). We found that, although V1 remained largely intact in brain-injured mice, there was ~35% reduction in the number of neurons that affected inhibitory cells more broadly than excitatory neurons. V1 neurons showed dramatically reduced activity, impaired responses to visual stimuli and weaker size selectivity and orientation tuning in vivo. Our results show a single, mild contusion injury produces profound and long-lasting impairments in the way V1 neurons encode visual input. These findings provide initial insight into cortical circuit dysfunction following central visual system neurotrauma.

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