Adult V1 Research Articles

Stimulus-specific enhancement in mouse visual cortex requires GABA but not VIP-peptide release from VIP interneurons.

When adult mice are repeatedly exposed to a particular visual stimulus for as little as 1 h per day for several days while their visual cortex (V1) is in the high-gain state produced by locomotion, that specific stimulus elicits much stronger responses in V1 neurons for the following several weeks, even when measured in anesthetized animals. Such stimulus-specific enhancement (SSE) is not seen if locomotion is prevented. The effect of locomotion on cortical responses is mediated by vasoactive intestinal peptide (VIP) positive interneurons, which can release both the peptide and the inhibitory neurotransmitter GABA. Previous studies have examined the role of VIP-ergic interneurons, but none have distinguished the individual roles of peptide from GABA release. Here, we used genetic ablation to determine which of those molecules secreted by VIP-ergic neurons is responsible for SSE. SSE was not impaired by VIP deletion but was prevented by compromising release of GABA from VIP cells. This finding suggests that SSE may result from Hebbian mechanisms that remain present in adult V1.NEW & NOTEWORTHY Many neurons package and release a peptide along with a conventional neurotransmitter. The conventional view is that such peptides exert late, slow effects on plasticity. We studied a form of cortical plasticity that depends on the activity of neurons that express both vasoactive intestinal peptide (VIP) and the inhibitory neurotransmitter GABA. GABA release accounted for their action on plasticity, with no effect of deleting the peptide on this phenomenon.

Impact of Monocular Retinal Lesions on Blob Size in Adult Human V1.

We studied the attributes of cytochrome c oxidase (CytOx)-rich blobs and ocular dominance columns (OD) in human V1 associated with monocular retinal lesions. Interblob distance, blob cross-sectional area, OD width, and OD arrangement pattern were analyzed in CytOx-reacted tangential sections of flat-mounted V1 preparations. Monocular deprivation induces differential expression of CytOx in the corresponding ODs in V1. We were thereby able to identify the V1 regions associated with the lesioned area in the retina, assign which OD was associated with each eye, and assign the corresponding blob in Layer III as deprived or nondeprived of visual input. We found that nondeprived blobs are more conspicuously stained than blobs outside the lesioned area. Notably, we found a selective expansion of blobs associated with the nonlesioned eye, whereas blobs associated with the deprived eye showed no significant change in size. Blob size in the latter condition was similar to the one observed in normal participants. These effects were present throughout the representation of the lesion in V1, suggesting that the underlying plasticity mechanisms do not depend on eccentricity. Retinal lesion caused no change in interblob distance, which was comparable to the normal brain (i.e., participants with no retinal lesion). This indicates that blob center is a stable hallmark of cortical organization. Finally, the width of ODs associated with the nonlesioned eye tended to be larger compared with ODs of the lesioned eye. However, this effect did not reach statistical significance. The stability of ODs thereby contrasts with blob plasticity, suggesting that the retinal lesion-triggered imbalance in the thalamocortical projection to Layer IVc has a limited impact on OD CytOx reactivity. On the other hand, we argue that ocular imbalance supports intracortical lateral competition that increases CytOx reactivity in the periblob region associated with the nonlesioned eye, accounting for the blob expansion we observe.

Selective plasticity of fast and slow excitatory synapses on somatostatin interneurons in adult visual cortex

Somatostatin-positive (SOM) interneurons are integral for shaping cortical processing and their dynamic recruitment is likely necessary for adaptation to sensory experience and contextual information. We found that excitatory synapses on SOMs in layer 2/3 (L2/3) of primary visual cortex (V1) of mice can be categorized into fast (F)- and slow (S)-Types based on the kinetics of the AMPA receptor-mediated current. Each SOM contains both types of synapses in varying proportions. The majority of local pyramidal neurons (PCs) make unitary connections with SOMs using both types, followed by those utilizing only S-Type, and a minority with only F-Type. Sensory experience differentially regulates synapses on SOMs, such that local F-Type synapses change with visual deprivation and S-Type synapses undergo plasticity with crossmodal auditory deprivation. Our results demonstrate that the two types of excitatory synapses add richness to the SOM circuit recruitment and undergo selective plasticity enabling dynamic adaptation of the adult V1.

Thalamic regulation of ocular dominance plasticity in adult visual cortex

Experience-dependent plasticity in the adult visual system is generally thought of as a cortical process. However, several recent studies have shown that perceptual learning or monocular deprivation can also induce plasticity in the adult dorsolateral geniculate nucleus (dLGN) of the thalamus. How plasticity in the thalamus and cortex interact in the adult visual system is ill-understood. To assess the influence of thalamic plasticity on plasticity in primary visual cortex (V1), we made use of our previous finding that during the critical period ocular dominance (OD) plasticity occurs in dLGN and requires thalamic synaptic inhibition. Using multielectrode recordings we find that this is also true in adult mice, and that in the absence of thalamic inhibition and plasticity, OD plasticity in adult V1 is absent. To study the influence of V1 on thalamic plasticity, we silenced V1 and show that during the critical period, but not in adulthood, the OD shift in dLGN is partially caused by feedback from V1. We conclude that during adulthood the thalamus plays an unexpectedly dominant role in experience-dependent plasticity in V1. Our findings highlight the importance of considering the thalamus as a potential source of plasticity in learning events that are typically thought of as cortical processes.

Thalamic regulation of ocular dominance plasticity in adult visual cortex.

Experience-dependent plasticity in the adult visual system is generally thought of as a cortical process. However, several recent studies have shown that perceptual learning or monocular deprivation can also induce plasticity in the adult dorsolateral geniculate nucleus (dLGN) of the thalamus. How plasticity in the thalamus and cortex interact in the adult visual system is ill-understood. To assess the influence of thalamic plasticity on plasticity in primary visual cortex (V1), we made use of our previous finding that during the critical period ocular dominance (OD) plasticity occurs in dLGN and requires thalamic synaptic inhibition. Using multielectrode recordings we find that this is also true in adult mice, and that in the absence of thalamic inhibition and plasticity, OD plasticity in adult V1 is absent. To study the influence of V1 on thalamic plasticity, we silenced V1 and show that during the critical period, but not in adulthood, the OD shift in dLGN is partially caused by feedback from V1. We conclude that during adulthood the thalamus plays an unexpectedly dominant role in experience-dependent plasticity in V1. Our findings highlight the importance of considering the thalamus as a potential source of plasticity in learning events that are typically thought of as cortical processes.

Corticotropin releasing factor neurons in the visual cortex mediate long-term changes in visual function induced by early adversity

Early adversity can cause malfunction of the visual system in adulthood. Adult female but not male mice undergoing early chronic mild stress (ECMS) maintain ocular dominance (OD) plasticity after the critical period. How early stressful experiences have a long-term impact on it is largely unknown. Here, we observed a wide distribution of corticotropin-releasing factor (CRF)-positive neurons, which mainly colocalized with a subpopulation of GABAergic interneurons in the mouse primary visual cortex (V1). Optogenetic activation of CRF-positive neurons transfected with AAV-ChR2 evoked inhibitory currents in nearby pyramidal cells. ECMS induced a reduction in the expression of CRF mRNA in adult mouse V1. Chemogenetic activation of V1 CRF neurons impaired OD plasticity in adult ECMS females. We further showed that local administration of the corticotropin releasing factor receptor 1 (CRFR1) antagonist via an osmotic minipump into the visual cortex mimicked OD plasticity in adult ECMS females. Whole-cell recording in layer 2/3 pyramidal neurons revealed that the CRFR1 antagonist reduced the short-term depression (STD) of evoked inhibitory postsynaptic current (IPSC) in females but not in males. Likewise, CRF agonists have the opposite effect. In summary, our findings indicate that the local CRF-CRFR1 system within V1 may mediate the long-term and sex-dependent effect of early stress experiences on visual plasticity and provide a target for the prevention of visual deficits in adults with a history of early-life adversity.

Existing function in primary visual cortex is not perturbed by new skill acquisition of a non-matched sensory task

Acquisition of new skills has the potential to disturb existing network function. To directly assess whether previously acquired cortical function is altered during learning, mice were trained in an abstract task in which selected activity patterns were rewarded using an optical brain-computer interface device coupled to primary visual cortex (V1) neurons. Excitatory neurons were longitudinally recorded using 2-photon calcium imaging. Despite significant changes in local neural activity during task performance, tuning properties and stimulus encoding assessed outside of the trained context were not perturbed. Similarly, stimulus tuning was stable in neurons that remained responsive following a different, visual discrimination training task. However, visual discrimination training increased the rate of representational drift. Our results indicate that while some forms of perceptual learning may modify the contribution of individual neurons to stimulus encoding, new skill learning is not inherently disruptive to the quality of stimulus representation in adult V1.

Construct validity, responsiveness, and utility of change indicators of the Dutch-Flemish PROMIS item banks for depression and anxiety administered as computerized adaptive test (CAT): A comparison with the Brief Symptom Inventory (BSI).

We evaluated construct validity, responsiveness, and utility of change indicators of the Dutch-Flemish PROMIS adult v1.0 item banks for Depression and Anxiety administered as computerized adaptive test (CAT). Specifically, the CATs were compared to the Brief Symptom Inventory (BSI) using pre- and re-test data of adult patients treated for common mental disorders (N = 400; median pre-to-re-test interval = 215 days). Construct validity was evaluated with Pearson's correlations and Cohen's ds; responsiveness with Pearson's correlations and pre-post effect sizes (ES); utility of change indicators with kappa coefficients and percentages of (dis)agreement. The results showed that the PROMIS CATs measure similar constructs as matching BSI scales. Under the assumption of measuring similar constructs, the CAT and BSI Depression scales were similarly responsive. For the Anxiety scales, we found a higher responsiveness for CAT (ES = 0.64) compared to the BSI (ES = 0.50). Finally, both CATs categorized the change scores of more patients as changed compared to matching BSI scales, indicating that the PROMIS CATs may be more able to detect actual change than the BSI. Based on these findings, the PROMIS CATs may be considered a modest improvement over matching BSI scales as tools for reviewing treatment progress with patients. We discuss several additional differences between the PROMIS CATs and the BSI to help test users choose instruments. These differences include the adopted measurement theory (Item Response Theory vs. Classical Test Theory), the mode of administration (CAT vs. fixed items), and the area of application (universal vs. predominantly clinical). (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Restoration of FMRP expression in adult V1 neurons rescues visual deficits in a mouse model of fragile X syndrome

Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABAA receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.

Rapid topographic reorganization in adult human primary visual cortex (V1) during noninvasive and reversible deprivation

Can the primary visual cortex (V1), once wired up in development, change in adulthood? Although numerous studies have demonstrated topographic reorganization in adult V1 following the loss of bottom-up input, others have challenged such findings, offering alternative explanations. Here we use a noninvasive and reversible deprivation paradigm and converging neural and behavioral approaches to address these alternatives in the experimental test case of short-term topographic reorganization in adult human V1. Specifically, we patched one eye in typical adults, thereby depriving the cortical representation of the other eye's blind spot (BS), and immediately tested for topographic reorganization using functional magnetic resonance imaging and psychophysics. Strikingly, within just minutes of eye-patching, the BS representation in V1 began responding to stimuli presented outside of the BS, and these same stimuli were perceived as elongated toward the BS. Thus, we provide converging neural and behavioral evidence of rapid topographic reorganization in adult human V1, and the strongest evidence yet that visual deprivation produces bona fide cortical change.

Experience-Dependent Changes in Myelin Basic Protein Expression in Adult Visual and Somatosensory Cortex.

An experience-driven increase in oligodendrocytes and myelin in the somatosensory cortex (S1) has emerged as a new marker of adult cortical plasticity. That finding contrasts with the view that myelin is a structural brake on plasticity, and that contributes to ending the critical period (CP) in the visual cortex (V1). Despite the evidence that myelin-derived signaling acts to end CP in V1, there is no information about myelin changes during adult plasticity in V1. To address this, we quantified the effect of three manipulations that drive adult plasticity (monocular deprivation (MD), fluoxetine treatment or the combination of MD and fluoxetine) on the expression of myelin basic protein (MBP) in adult rat V1. In tandem, we validated that environmental enrichment (EE) increased cortical myelin by measuring MBP in adult S1. For comparison with the MBP measurements, three plasticity markers were also quantified, the spine markers drebrin E and drebrin A, and a plasticity maintenance marker Ube3A. First, we confirmed that EE increased MBP in S1. Next, that expression of the plasticity markers was affected in S1 by EE and in V1 by the visual manipulations. Finally, we found that after adult MD, MBP increased in the non-deprived V1 hemisphere, but it decreased in the deprived hemisphere, and those changes were not influenced by fluoxetine. Together, the findings suggest that modulation of myelin expression in adult V1 may reflect the levels of visually driven activity rather than synaptic plasticity caused by adult plasticity.

Practical Significance of Longitudinal Measurement Invariance Violations in the Dutch-Flemish PROMIS Item Banks for Depression and Anxiety: An Illustration With Ordered-Categorical Data.

We investigated longitudinal measurement invariance in the Dutch-Flemish PROMIS adult v1.0 item banks for Depression and Anxiety using two clinical samples with mood and anxiety disorders (n = 640 and n = 528, respectively). Factor analysis was used to evaluate whether the item banks were sufficiently unidimensional at two test-occasions and whether the measured constructs remained the same over time. The results indicated that the item banks were sufficiently unidimensional, but the thresholds and residual variances of the constructs changed over time. However, using tentative rules of thumb, these invariance violations did not substantially affect the endorsement of a specific response category of a specific item at a specific test-occasion. Furthermore, the impact on the mean latent change scores of the item banks remained below the proposed cutoff value for substantial bias. These findings suggest that the invariance violations lacked practical significance for test-users, meaning that the item banks provide sufficiently invariant latent factor scores for use in clinical practice.

Perineuronal nets control visual input via thalamic recruitment of cortical PV interneurons.

In the neocortex, critical periods (CPs) of plasticity are closed following the accumulation of perineuronal nets (PNNs) around parvalbumin (PV)-positive inhibitory interneurons. However, how PNNs tune cortical function and plasticity is unknown. We found that PNNs modulated the gain of visual responses and γ-oscillations in the adult mouse visual cortex in vivo, consistent with increased interneuron function. Removal of PNNs in adult V1 did not affect GABAergic neurotransmission from PV cells, nor neuronal excitability in layer 4. Importantly, PNN degradation coupled to sensory input potentiated glutamatergic thalamic synapses selectively onto PV cells. In the absence of PNNs, increased thalamic PV-cell recruitment modulated feed-forward inhibition differently on PV cells and pyramidal neurons. These effects depended on visual input, as they were strongly attenuated by monocular deprivation in PNN-depleted adult mice. Thus, PNNs control visual processing and plasticity by selectively setting the strength of thalamic recruitment of PV cells.

Precocious deposition of perineuronal nets on Parvalbumin inhibitory neurons transplanted into adult visual cortex

The end of the critical period for primary visual cortex (V1) coincides with the deposition of perineuronal nets (PNN) onto Parvalbumin (PV) inhibitory neurons. Recently, we found that transplantation of embryonic inhibitory neurons into adult V1 reinstates a new critical period. Here we used Wisteria Floribunda Agglutinin (WFA) staining to compare the deposition of PNNs onto neurons during normal development and following transplantation at equivalent cell ages. In accord with previous findings, PV and PNN expression increases from negligible levels at postnatal day 14 (P14) to mature levels by P70. In contrast to P14, PNNs are found on transplanted PV neurons by 21 days after transplantation and persist to 105 days after transplantation. This precocious deposition was specific to PV neurons and excluded transplanted neurons expressing Somatostatin. Notably, the onset of PV expression in transplanted inhibitory neurons follows the timing of PV expression in juvenile V1. Moreover, transplantation has no discernible effect on host PNNs. The precocious deposition of PNNs onto transplanted PV neurons suggests that PNN expression identified by WFA does not reflect neuronal maturity and may be an inaccurate marker for transplant-induced plasticity of cortical circuits.

How Informative Are Self-Reported Adult Attention-Deficit/Hyperactivity Disorder Symptoms? An Examination of the Agreement Between the Adult Attention-Deficit/Hyperactivity Disorder Self-Report Scale V1.1 and Adult Attention-Deficit/Hyperactivity Disorder Investigator Symptom Rating Scale

Assess agreement between self-ratings via the adult attention-deficit/hyperactivity disorder (ADHD) Self-Report Scale (ASRS)-v1.1 Symptom Checklist and clinician ratings via the adult ADHD Investigator Symptom Rating Scale (AISRS) expanded version using DSM-5 adult ADHD patients (referred sample) and ADHD controls (recruited from a primary care physician practice). The ASRS v1.1 Symptom Checklist was administered to measure self-reported ADHD symptoms and impairment, the Adult ADHD Clinical Diagnostic Scale v1.2 was used to establish an adult ADHD diagnosis and the childhood and adult/current sections of the scale were used to provide scores to measure symptoms of childhood ADHD and recent symptoms of adult ADHD, the AISRS to measure ADHD current symptom severity. Participants (n = 299; range 18-58), of which 171 were ADHD+ and 128 ADHD-. ASRS and AISRS total scores and individual subsections examining inattention, hyperactivity, emotional dysfunction (EF), and emotional dyscontrol (EC) were all significantly correlated (Spearman's ρ's = 0.78-0.89, ps < 0.01). Correlations remained significant when controlling for demographic factors and psychiatric conditions. The ASRS (self) and AISRS (clinician rated) scales have high agreement. This agreement extended not only the to the core 18 DSM symptoms, but also to the additional 13 symptoms that examine EC and EF.

Development of a Computer Adaptive Test for Depression Based on the Dutch-Flemish Version of the PROMIS Item Bank.

We developed a Dutch-Flemish version of the patient-reported outcomes measurement information system (PROMIS) adult V1.0 item bank for depression as input for computerized adaptive testing (CAT). As item bank, we used the Dutch-Flemish translation of the original PROMIS item bank (28 items) and additionally translated 28 U.S. depression items that failed to make the final U.S. item bank. Through psychometric analysis of a combined clinical and general population sample ( N = 2,010), 8 added items were removed. With the final item bank, we performed several CAT simulations to assess the efficiency of the extended (48 items) and the original item bank (28 items), using various stopping rules. Both item banks resulted in highly efficient and precise measurement of depression and showed high similarity between the CAT simulation scores and the full item bank scores. We discuss the implications of using each item bank and stopping rule for further CAT development.

Lynx1 Limits Dendritic Spine Turnover in the Adult Visual Cortex.

Dendritic spine turnover becomes limited in the adult cerebral cortex. Identification of specific aspects of spine dynamics that can be unmasked in adulthood and its regulatory molecular mechanisms could provide novel therapeutic targets for inducing plasticity at both the functional and structural levels for robust recovery from brain disorders and injuries in adults. Lynx1, an endogenous inhibitor of nicotinic acetylcholine receptors, was previously shown to increase its expression in adulthood and thus to limit functional ocular dominance plasticity in adult primary visual cortex (V1). However, the role of this "brake" on spine dynamics is not known. We examined the contribution of Lynx1 on dendritic spine turnover before and after monocular deprivation (MD) in adult V1 with chronic in vivo imaging using two-photon microscopy and determined the spine turnover rate of apical dendrites of layer 5 (L5) and L2/3 pyramidal neurons in adult V1 of Lynx1 knock-out (KO) mice. We found that the deletion of Lynx1 doubled the baseline spine turnover rate, suggesting that the spine dynamics in the adult cortex is actively limited by the presence of Lynx1. After MD, adult Lynx1-KO mice selectively exhibit higher rate of spine loss with no difference in gain rate in L5 neurons compared with control wild-type counterparts, revealing a key signature of spine dynamics associated with robust functional plasticity in adult V1. Overall, Lynx1 could be a promising therapeutic target to induce not only functional, but also structural plasticity at the level of spine dynamics in the adult brain. Dendritic spine turnover becomes limited in the adult cortex. In mouse visual cortex, a premier model of experience-dependent plasticity, we found that the deletion of Lynx1, a nicotinic "brake" for functional plasticity, doubled the baseline spine turnover in adulthood, suggesting that the spine dynamics in the adult cortex is actively limited by Lynx1. After visual deprivation, spine loss, but not gain rate, remains higher in adult Lynx1 knock-out mice than in control wild-type mice, revealing a key signature of spine dynamics associated with robust functional plasticity. Lynx1 would be a promising target to induce not only functional, but also structural plasticity at the level of spine dynamics in adulthood.

Neural plasticity following lesions of the primate occipital lobe: The marmoset as an animal model for studies of blindsight.

For nearly a century it has been observed that some residual visually guided behavior can persist after damage to the primary visual cortex (V1) in primates. The age at which damage to V1 occurs leads to different outcomes, with V1 lesions in infancy allowing better preservation of visual faculties in comparison with those incurred in adulthood. While adult V1 lesions may still allow retention of some limited visual abilities, these are subconscious-a characteristic that has led to this form of residual vision being referred to as blindsight. The neural basis of blindsight has been of great interest to the neuroscience community, with particular focus on understanding the contributions of the different subcortical pathways and cortical areas that may underlie this phenomenon. More recently, research has started to address which forms of neural plasticity occur following V1 lesions at different ages, including work using marmoset monkeys. The relatively rapid postnatal development of this species, allied to the lissencephalic brains and well-characterized visual cortex provide significant technical advantages, which allow controlled experiments exploring visual function in the absence of V1. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 314-327, 2017.

Ocular Dominance Plasticity after Stroke Was Preserved in PSD-95 Knockout Mice.

Neuronal plasticity is essential to enable rehabilitation when the brain suffers from injury, such as following a stroke. One of the most established models to study cortical plasticity is ocular dominance (OD) plasticity in the primary visual cortex (V1) of the mammalian brain induced by monocular deprivation (MD). We have previously shown that OD-plasticity in adult mouse V1 is absent after a photothrombotic (PT) stroke lesion in the adjacent primary somatosensory cortex (S1). Exposing lesioned mice to conditions which reduce the inhibitory tone in V1, such as raising animals in an enriched environment or short-term dark exposure, preserved OD-plasticity after an S1-lesion. Here we tested whether modification of excitatory circuits can also be beneficial for preserving V1-plasticity after stroke. Mice lacking postsynaptic density protein-95 (PSD-95), a signaling scaffold present at mature excitatory synapses, have lifelong juvenile-like OD-plasticity caused by an increased number of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) -silent synapses in V1 but unaltered inhibitory tone. In fact, using intrinsic signal optical imaging, we show here that OD-plasticity was preserved in V1 of adult PSD-95 KO mice after an S1-lesion but not in PSD-95 wildtype (WT)-mice. In addition, experience-enabled enhancement of the optomotor reflex of the open eye after MD was compromised in both lesioned PSD-95 KO and PSD-95 WT mice. Basic V1-activation and retinotopic map quality were, however, not different between lesioned PSD-95 KO mice and their WT littermates. The preserved OD-plasticity in the PSD-95 KO mice indicates that V1-plasticity after a distant stroke can be promoted by either changes in excitatory circuitry or by lowering the inhibitory tone in V1 as previously shown. Furthermore, the present data indicate that an increased number of AMPA-silent synapses preserves OD-plasticity not only in the healthy brain, but also in another experimental paradigm of cortical plasticity, namely the long-range influence on V1-plasticity after an S1-lesion.

Optimal level activity of matrix metalloproteinases is critical for adult visual plasticity in the healthy and stroke-affected brain.

The ability of the adult brain to undergo plastic changes is of particular interest in medicine, especially regarding recovery from injuries or improving learning and cognition. Matrix metalloproteinases (MMPs) have been associated with juvenile experience-dependent primary visual cortex (V1) plasticity, yet little is known about their role in this process in the adult V1. Activation of MMPs is a crucial step facilitating structural changes in a healthy brain; however, upon brain injury, upregulated MMPs promote the spread of a lesion and impair recovery. To clarify these seemingly opposing outcomes of MMP-activation, we examined the effects of MMP-inhibition on experience-induced plasticity in healthy and stoke-affected adult mice. In healthy animals, 7-day application of MMP-inhibitor prevented visual plasticity. Additionally, treatment with MMP-inhibitor once but not twice following stroke rescued plasticity, normally lost under these conditions. Our data imply that an optimal level of MMP-activity is crucial for adult visual plasticity to occur.