Modulation of cofilin 1 phosphorylation induces juvenile-like plasticity in the adult mouse visual cortex

Modulation of cofilin 1 phosphorylation induces juvenile-like plasticity in the adult mouse visual cortex | bioRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-M677548'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Confirmatory Results Modulation of cofilin 1 phosphorylation induces juvenile-like plasticity in the adult mouse visual cortex Agustina Dapueto , Emilia Hayek , Alejo Acuña , Bruno Pannunzio , Leonel Gomez , Francesco M. Rossi doi: https://doi.org/10.1101/2025.05.05.652250 Agustina Dapueto 1 Laboratorio de Mecanismos de Neurodegeneración y Neuroprotección, Departamento de Neuroquímica, Instituto de Investigaciones Biológicas Clemente Estable , Montevideo, Uruguay Find this author on Google Scholar Find this author on PubMed Search for this author on this site Emilia Hayek 2 Laboratorio de Neurociencias “Unidad de Neuroplasticidad”, Instituto de Biología, Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de la República , Montevideo, Uruguay Find this author on Google Scholar Find this author on PubMed Search for this author on this site Alejo Acuña 2 Laboratorio de Neurociencias “Unidad de Neuroplasticidad”, Instituto de Biología, Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de la República , Montevideo, Uruguay Find this author on Google Scholar Find this author on PubMed Search for this author on this site Bruno Pannunzio 3 Departamento de Histología y Embriología, Facultad de Medicina, UdelaR / Laboratorio de Neuroinflamación y Terapia Génica del Institut Pasteur de Montevideo Find this author on Google Scholar Find this author on PubMed Search for this author on this site Leonel Gomez 4 Laboratorio de Neurociencias, Instituto de Biología, Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de la República , Montevideo, Uruguay Find this author on Google Scholar Find this author on PubMed Search for this author on this site Francesco M. Rossi 2 Laboratorio de Neurociencias “Unidad de Neuroplasticidad”, Instituto de Biología, Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de la República , Montevideo, Uruguay Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: fmrossi{at}fcien.edu.uy Abstract Full Text Info/History Metrics Supplementary material Preview PDF Abstract Cofilin 1 is an actin-depolymerizing protein that plays a fundamental role in actin dynamics, particularly within dendritic spines, where it has been implicated in both structural and functional plasticity. We recently demonstrated (by differential proteomics, western blot and immunohistochemistry) that the expression of cofilin 1 and its inactive phosphorylated form are dynamically regulated in the mouse visual cortex during postnatal development and by visual experience. Moreover, we found that cofilin 1 expression levels correlates with periods of heightened plasticity in the mouse visual cortex. In this study, we analyzed whether the pharmacological modulation of cofilin 1 activity affects plasticity processes in the visual cortex. Adult mice were treated with a synthetic peptide inhibitor of cofilin 1 activity (PCOF) or a control peptide (TAT) and then monocularly deprived of vision during 3 days. Following reopening of the deprived eye, structural plasticity was assessed by quantifying dendritic spine density using Golgi-like staining, and visual plasticity was evaluated by measuring visual acuity through the optomotor response test. Our results show that, in adult mice treated with the PCOF peptide - but not in controls - monocular deprivation led to a significant reduction in dendritic spine density in the contralateral visual cortex, as well as a decrease in visual acuity of the previously deprived eye. These findings indicate that cofilin 1 activity is crucial for the regulation of experience-dependent plasticity in the adult mouse visual cortex. Introduction The visual cortex is a paradigmatic model for studying experience-dependent plasticity. Several studies have shown that manipulating the visual input by a simple occlusion of vision in one eye for a few days (monocular deprivation, MD) induces dramatic and permanent changes in the visual cortex at both structural and functional level, as well as loss of vision. These effects are quite marked when MD is done during a particularly sensitive or critical period of postnatal life (CP), while they are reduced or absent when MD is done during adulthood ( Hensch, 2004 ; Levelt & Hubener, 2012 ). Over the past two decades, several studies have demonstrated that juvenile-like plasticity can be reinstated in adults through various treatments. Prominent examples of this phenomenon are, for instance, chronic fluoxetine administration, rearing in enriched environment, or feeding animals with caloric restriction ( Hensch et al., 1998 ; Fagiolini & Hensch, 2000 ; Pizzorusso et al., 2002 ). This discovery led to the successful employment of such treatments to facilitate recovery from visual pathology (e.g.: amblyopia) ( Sale et al., 2007 ; Maya-Vetencourt et al., 2008 ; Spolidoro et al., 2011 ; Baroncelli et al., 2012 ). The cellular and molecular mechanisms underlying the opening, duration and closure of the critical period and the processes controlling plasticity levels are still largely unknown. However, various studies pointed out that the development of the excitatory/inhibitory tone and the maturation of structural brakes in the visual cortex are fundamental players ( Hensch, 2005 ; Tropea et al., 2009 ; Fawcett et al., 2019 ). Large-scale studies (at both transcriptomic and proteomic levels) have suggested that a substantial number of genes regulate plasticity and that experience leaves distinct “molecular fingerprints” that vary according to the degree of cortical plasticity (see Rossi & Pizzorusso, 2025 for a review). Our group recently used a proteomic approach to identify protein profiles differentiating the visual cortex during the critical period (characterized by high plasticity) from adulthood (characterized by low plasticity), and following fluoxetine treatment in adults (characterized by pharmacologically-induced high plasticity) ( Ruiz-Perera, et al., 2015 ; Bornia et al., 2020 ). Among various differentially expressed proteins, cofilin 1 emerged as a relevant one as its levels were high, in correlation with high plasticity (critical period and fluoxetine treatment), and low, in correlation with low plasticity (adults). We further demonstrated by western blot and inmunohistochemistry that cofilin 1 and its inactivated form (phosphorylated in Ser3), are dynamically modulated during postnatal development and that MD affects their expression during the CP but not in adults ( Laguardia et al., 2023 ). These results suggested for the first time cofilin 1 as a potential player in the control of visual cortex plasticity. In the present work, we administered an inhibitory peptide targeting cofilin 1 activity to adult mice in vivo, and analyzed MD-induced effects in the visual cortex as marker of experience-dependent plasticity. Specifically, we investigated MD effects on structural parameters (dendritic spine density, using the Golgi-like staining), and on visual parameters (spatial resolution threshold, using the optomotor test). Our data indicate that cofilin 1 activity modulation reinstates high plasticity levels in the adult mouse visual cortex. Results Analysis of dendritic spine density in the mouse visual cortex with the Golgi-like staining We used the commercial elite Golgi kit (Bioenno) to stain and analyze spine density on apical dendrites of LII-III and LV pyramidal neurons of the binocular visual cortex. Following the fine-tuning of the methodology, we analyzed spine density in the visual cortex of untreated CP and adult mice (Supplementary Figure 1). We observed that spine density (n protrusions *100μm) in the visual cortex is higher in young mice than in adults, decreasing approx. 55% from CP to adulthood (CP, P28: 176.2±3.4, n=24 dendrites, n=5 mice, vs. AD, P58: 79.4±1.6, n=32 dendrites, n=5 mice, Student’s t-test, p<0.05). In order to confirm that the methodology in use allows the detection of plasticity at structural level, we compared the effects of MD on dendritic spine density between critical period and adult mice. CP and adult mice were deprived of vision in one eye (right eye) by lid suturing during 3 days from P28 to P31 and from P59 to P62, respectively. Then, mice were sacrificed and brains processed for Golgi-like staining (Supplementary Figure 2). We observed that during the critical period, MD reduces spine density in the contralateral vs. ipsilateral visual cortex of approximately 36% (contral.: 113.9±1.5 n=28 dendrites, vs. ipsil.: 178.0±3.7, n=24 dendrites, n=6 mice, Student’s t-test, p<0.05). On the contrary, no effects of MD were observed in adult mice (contral.: 86.4±3.1 n=24 dendrites, vs. ipsil.: 87.2±3.6, n=21 dendrites, n=6 mice, Student’s t-test, p=0,88), confirming that adult mice are less plastic than young ones. Modulation of cofilin activity reinstates experience-dependent structural plasticity in the adult mouse visual cortex Finally, in order to analyze if cofilin 1 plays a role in structural plasticity of the mouse visual cortex we made use of the pharmacological modulation of its activity by intravenous administration of a single dose of the PCOF inhibitory peptide or the TAT control peptide at a concentration of 15 pmol/g. First we checked if peptides treatment per se affected spine density in normal adult mice treated at P58 and analyzed 4 days later at P62 ( Figure 1 ). We observed no differences in spine density between the ispilateral (right) and the contralateral (left) visual cortex of adult mice treated with the TAT peptide (contral.: 82.2±1.9 n=19 dendrites vs. ipsil.: 81.0±1.4 n=19 dendrites, n=8 mice, Student’s t-test, p=0.60) or with the PCOF peptide (contral.: 84.2±1.7 n=19 dendrites vs. ipsil.: 83.0±1.5 n=19 dendrites, n=8 mice, Student’s t-test, p=0.63). Download figure Open in new tab Download figure Open in new tab Figure 1. Spine density is not affected by peptides administration in normal adult mice. Representative images of apical dendrites from the ispilateral and contralateral visual cortex of TAT treated (TATi and TATc) and PCOF treated (PCOFi and PCOFc) adult (AD) mice. Bar: 5 μm. The scatter plot represents the spine density (n protrusions*100 μm) in the ispilateral (TATi, right) and contralateral (TATc, left) visual cortex of n=8 adult mice treated with the TAT peptide, and in the ispilateral (PCOFi, right VC) and contralateral (PCOFc, left VC) visual cortex of n=8 adult mice treated with the PCOF peptide. Dots represent spine density values of individual dendrites; mean is marked as a bar±SEM. Mean spine density: TATi: 81.0±1.4 n=19 dendrites vs. TATc: 82.2±1.9 n=19 dendrites, n=8 mice, Student’s t-test, p=0.60; PCOFi: 83.0±1.5 n=19 dendrites vs. PCOFc: 84.2±1.7 n=19 dendrites, n=8 mice, Student’s t-test, p=0.63. Interestingly, we observed that treating adult mice with the PCOF peptide reinstates the juvenile-like MD induced effects at structural level. One day following PCOF treatment (P58), 3 days monocular deprivation (P59-62) reduces spine density in the contralateral vs. ipsilateral visual cortex of adult mice of approximately 42% (contral.: 49.4±1.6 n=37 dendrites vs. ipsil.: 84.9±2.5 n=37 dendrites, n=8 mice, Student’s t-test, p<0.05). On the contrary, no effects were observed in deprived adult mice treated with the control TAT peptide (contral.: 84.1±2.1 n=33 dendrites vs. ipsil.: 81.6±2.3 n=33 dendrites, n=8 mice, Student’s t-test, p=0,69) ( Figure 2 ). Download figure Open in new tab Download figure Open in new tab Figure 2. Monocular deprivation reduces spine density in the contralateral visual cortex in PCOF treated mice, but not in TAT treated ones. Representative images of apical dendrites from the ispilateral and contralateral visual cortex of TAT treated (TATi and TATc) and PCOF treated (PCOFi and PCOFc) deprived (MD, right eye) adult (AD) mice. Bar: 5 μm. The scatter plot represents the spine density (n protrusions*100 μm) in the ispilateral (TATi) and contralateral (TATc) visual cortex of n=8 deprived adult mice treated with the TAT peptide, and in the ispilateral (PCOFi) and contralateral (PCOFc) visual cortex of n=8 deprived adult mice treated with the PCOF peptide. Dots represent spine density values of individual dendrites; mean is marked as a bar±SEM. Mean spine density: TATi: 81.6±2.3 n=33 dendrites vs. TATc: 84.1±2.1 n=33 dendrites, n=8 mice, Student’s t-test, p=0.69; PCOFi: 84.9±2.5 n=37 dendrites vs. PCOFc: 49.4±1.6 n=37 dendrites, n=8 mice, Student’s t-test, *p<0.05. Analysis of spatial resolution threshold with the optomotor test We used the optomotor test to measure spatial resolution threshold of the left and right eye in unrestrained mice as an index of visual acuity ( Douglas et al., 2005 ). Following the fine-tuning of the methodology, we analyzed spatial resolution threshold (c/d) in CP and adult mice (Supplementary Figure 3). In agreement with previous studies ( Prusky et al., 2004 ), we observed that spatial resolution threshold is similar in critical period and adult mice (CP, P28: 0.37±0.01, n=6 mice, vs. AD, P60: 0.38±0.01, n=10 mice; Student’s t-test, p=0.85). In order to confirm that the optomotor test allows detecting experience-dependent plasticity changes of visual parameters, we verified if MD induces a modification of spatial resolution threshold comparing critical period and adult mice (Supplementary Figure 4). CP and adult mice were deprived of vision by lid suturing during 3 days from P28 to P31 and from P59 to P62, respectively, and then analyzed in the optomotor test. We found that during the critical period, MD reduces spatial resolution threshold in the deprived eye vs. the fellow eye of approximately 43% (fellow eye: 0.38±0.02 vs. MD eye: 0.20±0.01, n=6 mice, Student’s t-test, p<0.05). On the contrary, no effects of MD were observed in adult mice (fellow eye 0.39±0.01 vs. MD eye: 0.38±0.01, n=6 mice, Student’s t-test, p=0.81). Modulation of cofilin activity reinstates experience-dependent visual plasticity in the adult mouse visual cortex Finally, to analyze if cofilin 1 plays a role on the MD-induced effects on visual acuity of the mouse visual cortex we used the administration of the PCOF or the TAT peptide and analyzed spatial resolution threshold. We first checked the effects of peptides treatment in normal adult mice (treated at P58, analyzed at P62) ( Figure 3 ). We observed no differences on spatial resolution threshold between the two eyes in adult mice treated with the PCOF peptide (left eye: 0.39±0.01 vs. right eye: 0.39±0.01, n=6 mice, Student’s t-test, p=0.91) nor in TAT control-treated mice (left eye: 0.38±0.01 vs. right eye: 0.41±0.01, n=6 mice, Student’s t-test, p=0.89). Download figure Open in new tab Figure 3. Visual acuity is not affected by peptides administration in normal adult mice. The scatter plot represents the spatial resolution (c/d) through the left eye (TAT L) and the right eye (TAT R) of n=6 adult mice treated with the TAT peptide, and through the left eye (PCOF L) and the right eye (PCOF R) of n=6 adult mice treated with the PCOF peptide. Dots represent VA values of individual mice; mean is marked as a bar±SEM. Mean VA: TAT L: 0.38±0.01 vs. TAT R: 0.41±0.01, n=6, Student’s t-test, p=0.89; PCOF L: 0.39±0.01 vs. PCOF R: 0.39±0.01, n=6, Student’s t-test, p=0.91. On the contrary, we found that one day following PCOF peptide treatment (P58), 3 days monocular deprivation (P59-62) reduces spatial resolution threshold in the deprived eye vs. the fellow eye of approximately 31% (fellow eye: 0.38±0.01 vs. MD eye: 0.27±0.01, n=16 mice, Student’s t-test, p<0.05), while no effects were observed in deprived adult mice treated with the TAT control peptide (fellow eye: 0.39±0.01 vs. MD eye: 0.39±0.01, n=12 mice, Student’s t-test, p=0.81) ( Figure 4 ). Download figure Open in new tab Figure 4. Monocular deprivation reduces visual acuity through the deprived eye in PCOF treated mice, but not in TAT treated ones. The scatter plot represents the spatial resolution (c/d) through the fellow eye (TAT F) and the deprived eye (TAT MD) of n=12 adult (AD) mice treated with the TAT peptide, and through the fellow eye (PCOF F) and the deprived eye (PCOF MD) of n=16 adult mice treated with the PCOF peptide. Dots represent VA values of individual mice; mean is marked as a bar±SEM. Mean VA: TAT F: 0.39±0.01 vs. TAT MD: 0.39±0.01, n=12, Student’s t-test, p=0.81; PCOF F: 0.38±0.01 vs. PCOF MD: 0.27±0.01, n=16, Student’s t-test, *p<0.05. Materials and Methods Animals and treatment All experiments were performed in accordance with the EC Directive 86/609/EEC for animal experiments (directive from the European Commission of the European Economic Community) and with the Uruguayan Research Ethic Committees (protocol approval #1131, ExpFCien 2400 11-000556-20). A total of 74 C57BL6/J mice (both sexes) at different postnatal (P) ages (P28, n=16, P58: n=58) provided by the Unidad de Reactivos y Biomodelos de Experimentación, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay, were used. Mice were bred under specific pathogen-free conditions, housed (6/cage) in ventilated cages with positive pressure (20±1°C, relative humidity 40–60 %, 14/10 h. light-dark cycle), fed with standard mouse diet ad libitum , and had free access to water. Monocular deprivation Monocular deprivation was performed during 3 days in critical period (from P28 to P31) or in adult (from P58/59 to P61/62) mice anesthetized with ketamine / xylazine / acedan 100 / 10 / 3 mg/Kg, by suturing the eyelids of the right eye as previously described ( Laguardia et al., 2023 ). The integrity of the suture was checked daily and mice were used only if the eyelids remained closed throughout the duration of the deprivation period. The eyelids were reopened immediately before performing the optomotor test and the pupil was checked for clarity. Then mice were sacrificed (by cervical dislocation) and brain tissues collected. A total of 40 mice (P28: n=6, P58/59: n=34) was monocularly deprived of vision. Peptide treatment In order to modulate cofilin 1 phosphorylation in vivo we used a peptide (GenScript) consisting of the first 16 amino acids of cofilin 1 with the residue Ser3 phosphorylated ( Duffney et al., 2015 ). The phospho-cofilin peptide was coupled to the protein transduction domain of the HIV TAT protein to make it cell permeable (PCOF peptide: RKKRRQRRRMA{pSER}GVAVSDGVIKVFN). As a control, the peptide containing only the TAT-HIV domain was used (TAT peptide: RKKRRQRRR). Peptides were re-suspended in sterile water at a stock concentration of 2.5 mM, diluted in physiological solution at 5 microM (5 pmol/microL) and delivered by an intravenous injection (i.v.) at 15 pmol/g. A total of 44 mice (TAT: n=20, PCOF: n=24) was injected with peptides. Golgi staining Mice were sacrificed by cervical dislocation, brains were quickly removed, rinsed in physiological solution and were Golgi-stained using the élite Golgi Kit (#006690, Bioenno, Tech, LLC). Briefly, brains were immersed in the impregnation solution and stored at RT in darkness for 6 days. Brains were cut with a vibratome (LeicaGeoSystems VT1000S) in 150 μ m thick coronal sections that were collected in PB 0.1M (left and right visual cortex were separately collected). Sections were incubated free-floating in the staining and clarity solutions, rinsed in PBST 0.01M and directly mounted on gelatin-coated slides. Following dehydration (ethanol 95% and 100%) and cleaning (xylene), slides were covered with coverslips in mounting media (Canadian balsam, Biopack, or Entellan, Sigma-Aldrich). A total of 54 mice (CP: n=11, AD: n=43) was processed for Golgi staining. Spine density analysis Photographs of the images were obtained using a D70S Digital Camera (Nikon) attached to a Microphot-FXA microscope (Research Microscope, Nikon) with a 40x objective. Spine density analysis was carried out on apical dendrites of pyramidal neurons in layers II-III and V of the binocular visual cortex (bVC). bVC position was identified comparing sections with images from the mouse brain atlas ( Paxinos & Franklin, 2007 ; AP: −4.36 and −3.08; ML: 3.25 and 2.5). Nissl-stained alternating sections were used to identify cortical layers. Only dendrites of neurons showing typical pyramidal neuron morphology were analyzed (Braak & Braak, 1985; Spruston, 2008 ). Furthermore, in order to be analyzed dendrites must meet the following criteria: (i) to be viewed clearly, without significant breaks or interrupted staining; (ii) not to be interrupted by others stained neurons; (iii) the soma must be identifiable with clarity and be completely stained. Once the dendrites selected, the number of protrusions per 100 μm segment, along the entire dendrite was counted. Image analysis was carried out with the free software Fiji (Fiji Is Just ImageJ, NIH). Optomotor test Behavioral threshold acuity was evaluated using the optomotor task in unrestrained mice ( Prusky et al., 2004 ; Douglas et al., 2005 ). A virtual-reality chamber was created with four monitors facing into a square, a mirror in the floor and another in the roof of the chamber (with a small hole in its center were the camera was positioned). A platform was secured on the bottom of the floor (height 13 cm, diameter 5 cm). The stimulus (vertical sine-wave gratings) was projected on the monitors using the PsychoPy® software (PsychoPy v3.0, www.psychopy.org ). The stimulus changed in spatial frequency (0.1, 0.2., 0.3, 0.35, 0.375, 0.4, 0.425, 0.45 c/d; duration: 60 sec. each) and direction (alternating clockwise and counterclockwise, each 30 sec.) and was projected at 12 deg/sec. velocity and 100% contrast. The experiments were performed in scarce luminance room conditions (approx. 12 cd/m 2 ). All animals were habituated before the onset of testing by gentle handling and by placing them on the arena platform for a few minutes at a time. Experimenters were blind to treatments conditions of the mice and the animal’s previously recorded thresholds. Videos were analyzed counting number of head movements and comparing with the direction and frequency of the stimulus. Maximal spatial resolution visual threshold was taken as the last frequency at which mice responded in agreement with the direction of the stimulus. A total of 70 mice (CP: n=16, AD: n=54) was processed for the optomotor test. Discussion The present study aimed at investigating whether cofilin 1 plays a role in experience-dependent plasticity. Cofilin 1 is an actin-depolymerizing protein belonging to the ADF/cofilin family, which in mammals comprises three members: cofilin 1 (non-muscle, or n-cofilin), cofilin 2 (muscle-specific, or m-cofilin), and ADF (actin depolymerizing factor, also known as destrin). Among these, cofilin 1 and ADF are highly expressed in the brain, particularly at excitatory synapses ( Racz and Weinberg, 2006 ; Bellenchi et al., 2007 ; Rust et al., 2010 ; Görlich et al., 2011 ). The activity of ADF/cofilin is tightly regulated by phosphorylation at serine residue 3 (Ser3), which inhibits their binding to actin filaments - an important post-translational modification controlling their function ( Yang et al., 1998 ; Meng et al., 2002 ). Cofilin 1 plays a crucial role in actin filament turnover, especially within dendritic spines, where it has been extensively linked-primarily through studies in the hippocampus - to both structural and functional synaptic plasticity ( Rust, 2015 ; Bamburg et al., 2021 ; Namme et al., 2021 ). Different experimental strategies have been used to modulate cofilin 1 expression (knock out, conditional transgenic mutants, or interference RNA) or its activity (phospho-mimetic, or peptides administration) ( Shaw & Bamburg, 2017 ). Here we used the administration of a synthetic phosphorylated peptide that competes with the endogenous phosphorylated cofilin as a substrate for the slingshot phosphatase (SSH1) responsible for cofilin 1 dephosphorylation, thus determining a reduction in its activity ( Shaw & Bamburg, 2017 ). Previous works have shown that in vivo treatment with these peptides effectively induce a modulation of the phosphorylation state of cofilin 1 ( Aizawa et al., 2001 ; Toda et al., 2006 ; Wang et al., 2013 ; Zhou et al., 2014 ; Duffney et al., 2015 ; Rust, 2015 ; Tsubota et al., 2015 ; Deng et al., 2016 ). In order to study brain plasticity processes, we exploited the solid model of monocular deprivation to study structural and functional effects in the adult mouse visual cortex. We studied MD-effects on dendritic spine density as structural parameter and on visual acuity as physiological parameter. Initially, we confirmed that dendritic spine density decreases from the critical period to adulthood which is in agreement with previous studies and it is possibly related to the end of the postnatal pruning process ( Runge et al., 2020 ). We then verified if the experimental approach was able to detect plasticity at structural level and we found that MD decreases spine density when done in critical period mice but not in adults. These results confirmed previous works ( Mataga et al., 2004 ; Bochner et al., 2014 ; Bukhari et al., 2015 ; see also Djurisic et al., 2003; Hofer et al., 2009 ) and allowed the use of this experimental strategy to detect the potential effect of cofilin 1 on visual cortex plasticity at structural level. Finally we analyzed whether in vivo modulation of cofilin 1 activity restores sensitivity to MD in the adult visual cortex. We found that spine density decreases in the contralateral visual cortex of monocularly deprived adult mice treated with the PCOF peptide, which is the expected result for a treatment with a potential plasticity-increasing effect. A similar MD-induced decrease in cortical spine density has been observed by others for instance in adult Lynx1 (Bukari et al., 2015) and PSD95 ( Yusifov et al., 2021 ) knockout mice, demonstrating the role of these factors in cortical plasticity. Additionally, it was shown that sleep alterations can alter the elimination/formation ratio in monocularly deprived adult mice ( Zhou, et al., 2020 ). As for visual function, we used the optomotor test to detect spatial resolution threshold which is considered an index of visual acuity. While the optomotor response is a behavioral test reflecting sub-cortical and cortical function ( Douglas et al., 2005 ), the results obtained with such test have been shown to be consistent with electrophysiological cortical measures (such as visual evoked potentials) and to respond to experimental manipulations similarly ( Durand et al. 2012 ; Kang et al., 2013 ). We then showed that interfering with cofilin 1 activity decreases visual acuity in the deprived eye of adult mice. Besides electrophysiological VEP measures, other behavioral tests have been used to detect restored plasticity in adult rodents or recovery of vision in adult amblyopic animals. For example, it has been shown that fluoxetine or sub anesthetic ketamine administration, as well as enriched environment facilitate the recovery of normal visual acuity values (measured with the visual water maze task) in the deprived eye of amblyopic adult mice ( Sale et al., 2007 ; Maya-Vetencourt et al., 2008 ; Grieco et al., 2020 ). The present data indicate that cofilin 1 is a relevant player in the control of experience-plasticity in the mouse visual cortex as its modulation in vivo favors reopening of high plasticity levels at adult stages. These results are in agreement with previous works indicating a similar role of cofilin 1 in other brain areas or plasticity processes. It has been shown that cofilin 1 is important in hippocampal long-term depression/potentitation ( Cao et al., 2017 ), in transcolumnar plasticity of the somatosensory cortex ( Tsubota et al., 2015 ), as well as in memory processes ( Medina et al., 2020 ) (for reviews see: Rust, 2015 ; Shaw & Bamburg, 2017 ; Namme et al., 2021 ). Particularly lined-up with the present results is the study by Cerri et al., 2011 . In this work the authors used the bacterial protein toxin, cytotoxic necrotizing factor 1 (CNF1), to induce a persistent activation of Rho GTPases. They showed that in vivo administration of CNF1 reinstates ocular dominance plasticity in the adult rat visual cortex. Rho GTPases, mainly Rac1, Cdc42, and RhoA, are proteins that regulate actin activity. Interestingly, cofilin 1 activity is one of the effectors of RhoGTPases: Rac1 can activate LIMK1, while Rho and Cdc42 can activate LIMK2, the two main enzymes responsible for the phosphorylation, i.e. inactivation, of cofilin 1 ( Sumi et al., 1999 ; Name et al., 2021). One possible interpretation of these findings is that the CNF1-induced restoration of high plasticity levels in adult mice is partially mediated by reduced cofilin 1 activity, reflected by an increase in its phosphorylated (inactive) form. This interpretation is supported by our results showing that administration of the PCOF peptide - which enhances endogenous phosphocofilin levels by inhibiting the corresponding phosphatase - promotes cortical plasticity. In summary, our findings highlight a critical role for cofilin 1 activity in regulating experience-dependent plasticity in the mouse visual cortex. However, the precise molecular mechanisms by which cofilin 1 exerts these effects remain to be elucidated. Acknowledgements This work was supported by Programa de Desarrollo de las Ciencias Básicas (Pedeciba), Agencia Nacional de Investigación a Innovación (ANII), and Comisión Sectorial de Investigación Científica (CSIC). The authors wish to thank Dr. F. Zolessi, Dr. L. Gomez and Dr. A. Villarino (Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay) for experimental support and assistance, and for providing comments on the manuscript; Dr. R. Mazziotti, L. Baroncelli and T. Pizzorusso (Scuola Normale Superiore/Institute of Neuroscience, CNR, Pisa, Italy) for assisting in the setting-up of the optomotor response test. F. M. Rossi: Conceptualization, Methodology, Software, Data curation, Writing, Original draft preparation, Supervision, Reviewing and Editing, Funding acquisition; A. Dapueto, L. Gomez, E. Hayek, A. Acuña, B. Pannunzio: Investigation, Visualization. A. Dapueto was supported by a CSIC grant (#567, Proyecto de Iniciación a la Investigación). The authors confirm that the funders had no influence over the study design, content of the article, or selection of this journal. Footnotes ↵ & First co-authorship Email: agustinadapueto{at}gmail.com Email: hayekemilia03{at}gmail.com Email: alejoacu{at}gmail.com Email: leonel.gomez{at}gmail.com Email: brunopannunzio{at}gmail.com Figure 2 revised Supplementary Figure 2 revised References shortened References ↵ Aizawa H , Wakatsuki S , Ishii A , Moriyama K , Sasaki Y , Ohashi K , Sekine-Aizawa Y , Sehara-Fujisawa A , Mizuno K , Goshima Y , Yahara I. Phosphorylation of cofilin by LIM-kinase is necessary for semaphorin 3A-induced growth cone collapse . Nat Neurosci . 2001 Apr ; 4 ( 4 ): 367 – 73 . doi: 10.1038/86011 . OpenUrl CrossRef PubMed Web of Science ↵ Bamburg JR , Minamide LS , Wiggan O , Tahtamouni LH , Kuhn TB . Cofilin and Actin Dynamics: Multiple Modes of Regulation and Their Impacts in Neuronal Development and Degeneration . Cells . 2021 Oct 12 ; 10 ( 10 ): 2726 . doi: 10.3390/cells10102726 . OpenUrl CrossRef ↵ Baroncelli L , Bonaccorsi J , Milanese M , Bonifacino T , Giribaldi F , Manno I , Cenni MC , Berardi N , Bonanno G , Maffei L , Sale A. Enriched experience and recovery from amblyopia in adult rats: impact of motor, social and sensory components . Neuropharmacology . 2012 Jun ; 62 ( 7 ): 2388 – 97 . doi: 10.1016/j.neuropharm.2012.02.010 . OpenUrl CrossRef PubMed Web of Science ↵ Bellenchi GC , Gurniak CB , Perlas E , Middei S , Ammassari-Teule M , Witke W. N-cofilin is associated with neuronal migration disorders and cell cycle control in the cerebral cortex . Genes Dev . 2007 Sep 15 ; 21 ( 18 ): 2347 – 57 . doi: 10.1101/gad.434307 . OpenUrl Abstract / FREE Full Text ↵ Bochner DN , Sapp RW , Adelson JD , Zhang S , Lee H , Djurisic M , Syken J , Dan Y , Shatz CJ . Blocking PirB up-regulates spines and functional synapses to unlock visual cortical plasticity and facilitate recovery from amblyopia . Sci Transl Med . 2014 Oct 15 ; 6 ( 258 ): 258ra140 . doi: 10.1126/scitranslmed.3010157 . OpenUrl Abstract / FREE Full Text ↵ Bornia N , Taboada A , Dapueto A , Rossi FM . Identification of cofilin 1 as a candidate protein associated to mouse visual cortex plasticity . Neurosci Lett . 2020 Jul 13 ; 731 : 135056 . doi: 10.1016/j.neulet.2020.135056 . OpenUrl CrossRef PubMed Braak H , Braak E. Golgi preparations as a tool in neuropathology with particular reference to investigations of the human telencephalic cortex . Progress in Neurobiology , 25 ( 2 ), 93 – 139 . doi: 10.1016/0301-0082(85)90001-2 OpenUrl CrossRef PubMed Web of Science ↵ Bukhari N , Burman PN , Hussein A , Demars MP , Sadahiro M , Brady DM , Tsirka SE , Russo SJ , Morishita H. Unmasking Proteolytic Activity for Adult Visual Cortex Plasticity by the Removal of Lynx1 . J Neurosci . 2015 Sep 16 ; 35 ( 37 ): 12693 – 702 . doi: 10.1523/JNEUROSCI.4315-14.2015 . OpenUrl Abstract / FREE Full Text ↵ Cao F , Zhou Z , Pan X , Leung C , Xie W , Collingridge G , Jia Z. Developmental regulation of hippocampal long-term depression by cofilin-mediated actin reorganization . Neuropharmacology . 2017 Jan ; 112 ( Pt A ): 66 – 75 . doi: 10.1016/j.neuropharm.2016.08.017 . OpenUrl CrossRef PubMed ↵ Cerri C , Fabbri A , Vannini E , Spolidoro M , Costa M , Maffei L , Fiorentini C , Caleo M. Activation of Rho GTPases triggers structural remodeling and functional plasticity in the adult rat visual cortex . J Neurosci . 2011 Oct 19 ; 31 ( 42 ): 15163 – 72 . doi: 10.1523/JNEUROSCI.2617-11.2011 . OpenUrl Abstract / FREE Full Text ↵ Deng Y , Wei J , Cheng J , Zhong P , Xiong Z , Liu A , Lin L , Chen S , Yan Z. Partial Amelioration of Synaptic and Cognitive Deficits by Inhibiting Cofilin Dephosphorylation in an Animal Model of Alzheimer’s Disease . J Alzheimers Dis . 2016 Jun 28 ; 53 ( 4 ): 1419 – 32 . doi: 10.3233/JAD-160167 . OpenUrl CrossRef PubMed Djurisic M , Vidal GS , Mann M , Aharon A , Kim T , Ferrao Santos A , Zuo Y , Hübener M , Shatz CJ . PirB regulates a structural substrate for cortical plasticity . Proc Natl Acad Sci U S A . 2013 Dec 17 ; 110 ( 51 ): 20771 – 6 . doi: 10.1073/pnas.1321092110 . OpenUrl Abstract / FREE Full Text ↵ Douglas RM , Alam NM , Silver BD , McGill TJ , Tschetter WW , Prusky GT . Independent visual threshold measurements in the two eyes of freely moving rats and mice using a virtual-reality optokinetic system . Vis Neurosci . 2005 Sep-Oct ; 22 ( 5 ): 677 – 84 . doi: 10.1017/S0952523805225166 . OpenUrl CrossRef PubMed Web of Science ↵ Duffney LJ , Zhong P , Wei J , Matas E , Cheng J , Qin L , Ma K , Dietz DM , Kajiwara Y , Buxbaum JD , Yan Z. Autism-like Deficits in Shank3-Deficient Mice Are Rescued by Targeting Actin Regulators . Cell Rep . 2015 Jun 9 ; 11 ( 9 ): 1400 – 1413 . doi: 10.1016/j.celrep.2015.04.064 . OpenUrl CrossRef PubMed ↵ Durand S , Patrizi A , Quast KB , Hachigian L , Pavlyuk R , Saxena A , Carninci P , Hensch TK , Fagiolini M. NMDA receptor regulation prevents regression of visual cortical function in the absence of Mecp2 . Neuron . 2012 Dec 20 ; 76 ( 6 ): 1078 – 90 . doi: 10.1016/j.neuron.2012.12.004 . OpenUrl CrossRef PubMed Web of Science ↵ Fagiolini M , Hensch TK . Inhibitory threshold for critical-period activation in primary visual cortex . Nature . 2000 Mar 9 ; 404 ( 6774 ): 183 – 6 . doi: 10.1038/35004582 . OpenUrl CrossRef PubMed Web of Science ↵ Fawcett JW , Oohashi T , Pizzorusso T. The roles of perineuronal nets and the perinodal extracellular matrix in neuronal function . Nat Rev Neurosci . 2019 Aug ; 20 ( 8 ): 451 – 465 . doi: 10.1038/s41583-019-0196-3 . OpenUrl CrossRef PubMed ↵ Görlich A , Wolf M , Zimmermann AM , Gurniak CB , Al Banchaabouchi M , Sassoè-Pognetto M , Witke W , Friauf E , Rust MB . N-cofilin can compensate for the loss of ADF in excitatory synapses . PLoS One . 2011 ; 6 ( 10 ): e26789 . doi: 10.1371/journal.pone.0026789 . OpenUrl CrossRef PubMed ↵ Grieco SF , Qiao X , Zheng X , Liu Y , Chen L , Zhang H , Yu Z , Gavornik JP , Lai C , Gandhi SP , Holmes TC , Xu X. Subanesthetic Ketamine Reactivates Adult Cortical Plasticity to Restore Vision from Amblyopia . Curr Biol . 2020 Sep 21 ; 30 ( 18 ): 3591 – 3603.e8 . doi: 10.1016/j.cub.2020.07.008 . OpenUrl CrossRef PubMed ↵ Hensch TK . Critical period regulation . Annu Rev Neurosci . 2004 ; 27 : 549 – 79 . doi: 10.1146/annurev.neuro.27.070203.144327 . OpenUrl CrossRef PubMed Web of Science ↵ Hensch TK . Critical period mechanisms in developing visual cortex . Curr Top Dev Biol . 2005 ; 69 : 215 – 37 . doi: 10.1016/S0070-2153(05)69008-4 . OpenUrl CrossRef PubMed Web of Science ↵ Hensch TK , Fagiolini M , Mataga N , Stryker MP , Baekkeskov S , Kash SF . Local GABA circuit control of experience-dependent plasticity in developing visual cortex . Science . 1998 Nov 20 ; 282 ( 5393 ): 1504 – 8 . doi: 10.1126/science.282.5393.1504 . OpenUrl Abstract / FREE Full Text ↵ Hofer SB , Mrsic-Flogel TD , Bonhoeffer T , Hübener M. Experience leaves a lasting structural trace in cortical circuits . Nature . 2009 Jan 15 ; 457 ( 7227 ): 313 – 7 . doi: 10.1038/nature07487 . OpenUrl CrossRef PubMed Web of Science ↵ Kang E , Durand S , LeBlanc JJ , Hensch TK , Chen C , Fagiolini M. Visual acuity development and plasticity in the absence of sensory experience . J Neurosci . 2013 Nov 6 ; 33 ( 45 ): 17789 – 96 . doi: 10.1523/JNEUROSCI.1500-13.2013 . OpenUrl Abstract / FREE Full Text ↵ Laguardia A , Dapueto A , McCuistion H , Rossi FM . Cofilin 1 Is Dynamically Modulated During Postnatal Development and by Visual Input in the Mouse Visual Cortex . Neuroscience . 2023 Feb 1 ; 510 : 147 – 156 . doi: 10.1016/j.neuroscience.2022.11.024 . OpenUrl CrossRef PubMed ↵ Levelt CN , Hübener M. Critical-period plasticity in the visual cortex . Annu Rev Neurosci . 2012 ; 35 : 309 – 30 . doi: 10.1146/annurev-neuro-061010-113813 . OpenUrl CrossRef PubMed Web of Science ↵ Mataga N , Mizuguchi Y , Hensch TK . Experience-dependent pruning of dendritic spines in visual cortex by tissue plasminogen activator . Neuron . 2004 Dec 16 ; 44 ( 6 ): 1031 – 41 . doi: 10.1016/j.neuron.2004.11.028 . OpenUrl CrossRef PubMed Web of Science ↵ Maya Vetencourt JF , Sale A , Viegi A , Baroncelli L , De Pasquale R , O’Leary OF , Castrén E , Maffei L. The antidepressant fluoxetine restores plasticity in the adult visual cortex . Science . 2008 Apr 18 ; 320 ( 5874 ): 385 – 8 . doi: 10.1126/science.1150516 . OpenUrl Abstract / FREE Full Text ↵ Medina C , de la Fuente V , Tom Dieck S , Nassim-Assir B , Dalmay T , Bartnik I , Lunardi P , de Oliveira Alvares L, Schuman EM , Letzkus JJ , Romano A. LIMK, Cofilin 1 and actin dynamics involvement in fear memory processing . Neurobiol Learn Mem . 2020 Sep ; 173 : 107275 . doi: 10.1016/j.nlm.2020.107275 . OpenUrl CrossRef PubMed ↵ Meng Y , Zhang Y , Tregoubov V , Janus C , Cruz L , Jackson M , Lu WY , MacDonald JF , Wang JY , Falls DL , Jia Z. Abnormal spine morphology and enhanced LTP in LIMK-1 knockout mice . Neuron . 2002 Jul 3 ; 35 ( 1 ): 121 – 33 . doi: 10.1016/s0896-6273(02)00758-4 . OpenUrl CrossRef PubMed Web of Science ↵ Namme JN , Bepari AK , Takebayashi H. Cofilin Signaling in the CNS Physiology and Neurodegeneration . Int J Mol Sci . 2021 Oct 3 ; 22 ( 19 ): 10727 . doi: 10.3390/ijms221910727 . OpenUrl CrossRef ↵ Paxinos G , Franklin K. The mouse brain in stereotaxic coordinates . Oxford, UK , Gulf Professional Publishing , 2007 . ↵ Pizzorusso T , Medini P , Berardi N , Chierzi S , Fawcett JW , Maffei L. Reactivation of ocular dominance plasticity in the adult visual cortex . Science . 2002 Nov 8 ; 298 ( 5596 ): 1248 – 51 . doi: 10.1126/science.1072699 . OpenUrl Abstract / FREE Full Text ↵ Prusky GT , Alam NM , Beekman S , Douglas RM . Rapid quantification of adult and developing mouse spatial vision using a virtual optomotor system . Invest Ophthalmol Vis Sci . 2004 Dec ; 45 ( 12 ): 4611 – 6 . doi: 10.1167/iovs.04-0541 . OpenUrl Abstract / FREE Full Text ↵ Racz B , Weinberg RJ . Spatial organization of cofilin in dendritic spines . Neuroscience . 2006 ; 138 ( 2 ): 447 – 56 . doi: 10.1016/j.neuroscience.2005.11.025 . OpenUrl CrossRef PubMed Web of Science ↵ Rossi FM , Pizzorusso T. Neuroproteomics applied to the study of visual cortex plasticity . Neuroscience 2025 , in press. ↵ Ruiz-Perera L , Muniz M , Vierci G , Bornia N , Baroncelli L , Sale A , Rossi FM . Fluoxetine increases plasticity and modulates the proteomic profile in the adult mouse visual cortex . Sci Rep . 2015 Jul 24 ; 5 : 12517 . doi: 10.1038/srep12517 . OpenUrl CrossRef PubMed ↵ Runge K , Cardoso C , de Chevigny A. Dendritic Spine Plasticity: Function and Mechanisms . Front Synaptic Neurosci . 2020 Aug 28 ; 12 : 36 . doi: 10.3389/fnsyn.2020.00036 . OpenUrl CrossRef PubMed ↵ Rust MB . ADF/cofilin: a crucial regulator of synapse physiology and behavior . Cell Mol Life Sci . 2015 Sep ; 72 ( 18 ): 3521 – 9 . doi: 10.1007/s00018-015-1941-z . OpenUrl CrossRef PubMed ↵ Rust MB , Gurniak CB , Renner M , Vara H , Morando L , Görlich A , Sassoè-Pognetto M , Banchaabouchi MA , Giustetto M , Triller A , Choquet D , Witke W. Learning, AMPA receptor mobility and synaptic plasticity depend on n-cofilin-mediated actin dynamics . EMBO J . 2010 Jun 2 ; 29 ( 11 ): 1889 – 902 . doi: 10.1038/emboj.2010.72 . OpenUrl Abstract / FREE Full Text ↵ Sale A , Maya Vetencourt JF , Medini P , Cenni MC , Baroncelli L , De Pasquale R , Maffei L. Environmental enrichment in adulthood promotes amblyopia recovery through a reduction of intracortical inhibition . Nat Neurosci . 2007 Jun ; 10 ( 6 ): 679 – 81 . doi: 10.1038/nn1899 . OpenUrl CrossRef PubMed Web of Science ↵ Shaw AE , Bamburg JR . Peptide regulation of cofilin activity in the CNS: A novel therapeutic approach for treatment of multiple neurological disorders . Pharmacol Ther . 2017 Jul ; 175 : 17 – 27 . doi: 10.1016/j.pharmthera.2017.02.031 . OpenUrl CrossRef PubMed ↵ Spolidoro M , Baroncelli L , Putignano E , Maya-Vetencourt JF , Viegi A , Maffei L. Food restriction enhances visual cortex plasticity in adulthood . Nat Commun . 2011 ; 2 : 320 . doi: 10.1038/ncomms1323 . OpenUrl CrossRef PubMed ↵ Spruston N. Pyramidal neurons: dendritic structure and synaptic integration . Nat Rev Neurosci . 2008 Mar ; 9 ( 3 ): 206 – 21 . doi: 10.1038/nrn2286 . OpenUrl CrossRef PubMed Web of Science ↵ Sumi T , Matsumoto K , Takai Y , Nakamura T. Cofilin phosphorylation and actin cytoskeletal dynamics regulated by rho- and Cdc42-activated LIM-kinase 2 . J Cell Biol . 1999 Dec 27 ; 147 ( 7 ): 1519 – 32 . doi: 10.1083/jcb.147.7.1519 . OpenUrl Abstract / FREE Full Text ↵ Toda S , Shen HW , Peters J , Cagle S , Kalivas PW . Cocaine increases actin cycling: effects in the reinstatement model of drug seeking . J Neurosci . 2006 Feb 1 ; 26 ( 5 ): 1579 – 87 . doi: 10.1523/JNEUROSCI.4132-05.2006 . OpenUrl Abstract / FREE Full Text ↵ Tropea D , Van Wart A , Sur M. Molecular mechanisms of experience-dependent plasticity in visual cortex . Philos Trans R Soc Lond B Biol Sci . 2009 Feb 12 ; 364 ( 1515 ): 341 – 55 . doi: 10.1098/rstb.2008.0269 . OpenUrl CrossRef PubMed ↵ Tsubota T , Okubo-Suzuki R , Ohashi Y , Tamura K , Ogata K , Yaguchi M , Matsuyama M , Inokuchi K , Miyashita Y. Cofilin1 controls transcolumnar plasticity in dendritic spines in adult barrel cortex . PLoS Biol . 2015 Feb 27 ; 13 ( 2 ): e1002070 . doi: 10.1371/journal.pbio.1002070 . OpenUrl CrossRef PubMed ↵ Wang Y , Dong Q , Xu XF , Feng X , Xin J , Wang DD , Yu H , Tian T , Chen ZY . Phosphorylation of cofilin regulates extinction of conditioned aversive memory via AMPAR trafficking . J Neurosci . 2013 Apr 10 ; 33 ( 15 ): 6423 – 33 . doi: 10.1523/JNEUROSCI.5107-12.2013 . OpenUrl Abstract / FREE Full Text ↵ Yang N , Higuchi O , Ohashi K , Nagata K , Wada A , Kangawa K , Nishida E , Mizuno K. Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization . Nature . 1998 Jun 25 ; 393 ( 6687 ): 809 – 12 . doi: 10.1038/31735 . OpenUrl CrossRef PubMed Web of Science ↵ Yusifov R , Tippmann A , Staiger JF , Schlüter OM , Löwel S. Spine dynamics of PSD-95-deficient neurons in the visual cortex link silent synapses to structural cortical plasticity . Proc Natl Acad Sci U S A . 2021 Mar 9 ; 118 ( 10 ): e2022701118 . doi: 10.1073/pnas.2022701118 . OpenUrl Abstract / FREE Full Text ↵ Zhou Y , Lai CSW , Bai Y , Li W , Zhao R , Yang G , Frank MG , Gan WB . REM sleep promotes experience-dependent dendritic spine elimination in the mouse cortex . Nat Commun . 2020 Sep 23 ; 11 ( 1 ): 4819 . doi: 10.1038/s41467-020-18592-5 . OpenUrl CrossRef PubMed ↵ Zhou GL , Zhang H , Wu H , Ghai P , Field J. Phosphorylation of the cytoskeletal protein CAP1 controls its association with cofilin and actin . J Cell Sci . 2014 Dec 1 ; 127 ( Pt 23 ): 5052 – 65 . doi: 10.1242/jcs.156059 . OpenUrl Abstract / FREE Full Text Back to top Previous Next Posted May 19, 2025. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. 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