Genetic Otx2 mis-localization delays critical period plasticity across brain regions

Lee, Henry H.C.; Bernard, C.; Ye, Z; Acampora, Dario; Simeone, Antonio; Prochiantz, Alain; Nardo, Ariel A. Di; Hensch, Takao K.

doi:10.1038/mp.2017.1

Cited by 71 publications

(107 citation statements)

References 64 publications

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“…The PNN accumulates postnatally to reach adult density at P50 in the V1 area of the mouse visual cortex (Ye et al, 2018;Lee et al, 2017;Lensjø et al, 2017b). In order to test the hypothesis that targeted chemogenetic inhibition of PV interneurons alters adult PNN density, we adapted the protocol known to reinstate visual plasticity at P35 (Kuhlman et al, 2013) to measure PNN changes between P58 and P61 (see Methods and Fig.S1).…”

Section: Targeted Chemogenetic Inhibition Of Pv Interneurons Induces mentioning

confidence: 99%

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

Devienne

Picaud

Cohen

et al. 2019

Preprint

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Perineuronal 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 activitydependent mechanism to control the local remodeling of adult cortical circuits.

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Section: Targeted Chemogenetic Inhibition Of Pv Interneurons Induces mentioning

confidence: 99%

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

Devienne

Picaud

Cohen

et al. 2019

Preprint

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“…During mouse late postnatal development, the privileged accumulation of OTX2 within FSPV cells in the visual cortex opens plasticity for binocular vision at P20 and closes it by P40 (17). This critical period of plasticity is thus regulated by non-cell autonomous OTX2, a phenomenon that was recently extended to the auditory cortex and medial prefrontal cortex (mPFC) (18). For the visual cortex, it was also shown that pharmacological or genetic decreases of FSPV cell OTX2 content in the adult cortex reopens a window of plasticity, allowing for the recovery of binocular vision in mice made amblyopic by the closure of one eye during the juvenile critical period (14; 15).…”

Section: Introductionmentioning

confidence: 99%

Non-cell autonomous OTX2 transcription factor regulates anxiety-related behavior in the mouse

Vincent

Gilabert-Juan

Gibel-Russo

et al. 2019

Preprint

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The Otx2 homeoprotein transcription factor is expressed in the dopaminergic neurons of the ventral tegmental area, a mesencephalic nucleus involved in the control of complex behaviors through its projections to limbic structures, including the ventral hippocampus, amygdala, nucleus accumbens and prefrontal cortex. We find adult mice heterozygous for Otx2 show a hypoanxious phenotype in light-dark box and elevated plus maze paradigms. However, the number of dopaminergic neurons, the integrity of their axons, their projection patterns in target structures, and the amounts of dopamine and dopamine metabolites in targets structures were not modified in the Otx2 mutant. Because OTX2 is expressed by the choroid plexus, secreted into cerebrospinal fluid and transferred to parvalbumin interneurons of the cortex, hippocampus, and amygdala, we investigated if the hypoanxiety of Otx2 heterozygous mice could result from the decreased synthesis of Otx2 in the choroid plexus. Indeed, hypoanxious phenotype was reversed by the overexpression of Otx2 specifically in choroid plexus of adult Otx2 heterozygous mice, while hypoanxious phenotype could be induced in adult wild type mice by lowering OTX2 levels in the cerebrospinal fluid. Taken together, OTX2 synthesis by the choroid plexus followed by its secretion into the cerebrospinal fluid is an important regulator of the anxiety phenotype in the mouse. MATERIAL AND METHODS Ethics statementAll animal procedures, including housing, were carried out in accordance with the recommendations of the European Economic Community (86/609/EEC), the French National Committee (87/848) and French bylaws (AGRG1240332A / AGRG1238724A / AGRG1238767A / AGRG1238729A / AGRG1238753A). For surgical procedures, animals were anesthetized with Xylazine (Rompun 2%, 5 mg/kg) and Ketamine (Imalgene 500, 80 mg/kg). This research (project no. 00704.02) was approved by Ethics committee n° 59 of the French Ministry for Research and Higher Education. MiceThe Otx2-het mouse line was generated in the laboratory of Antonio Simeone (CEINGE, Naples), with the Otx2 coding sequence and introns replaced by GFP (20). Otx2 +/GFP males were crossed with B6D2F1 females to obtain Otx2-het mice. The single-chain antibody (scFv) OTX2 knock-in scFv-Otx2 mouse line was generated by the Institut Clinique de la Souris (Strasbourg, France) by inserting the scFv-Otx2 minigene construct in the Rosa26 locus (21). Mice were raised in a 12-hour light/dark cycle with 2 to 5 (males) or 6 (females) animals per cages. Temperature was controlled (21±3°C), and food and water provided ad libitum. AAV injectionsAdeno-associated viruses (AAV) were generated by Vector Biolabs: AAV5(CMV)-HAOtx2-2A-mCherry and AAV5(CMV)-mCherry. Stereotaxic injections were performed with a Hamilton syringe at a rate of 0.3 µl/min: 2 µl/lateral ventricle (bregma: x = ±1.28 mm, y = -0.58 mm, z = 2 mm). Mice were tested in the light-dark box and on the elevated-plus maze 3 and 4 weeks after injection, respectively. Cre-TAT protein injectionStereotaxic injection (bregma:...

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“…6 Although these trajectories appear to be distinct, recent evidence suggests that transient, stress-induced perturbations in transcriptional programs during sensitive periods may influence susceptibility to later life stressors 7 or prolong the sensitive period altogether. 8 It is likely that both early and later life stress may exert lasting negative influences on transcription, cell functioning and behavior, through common epigenetic mechanisms.…”

Section: Introductionmentioning

confidence: 99%

A role for activity‐dependent epigenetics in the development and treatment of major depressive disorder

Nagy

Vaillancourt

Turecki

2018

Genes Brain and Behavior

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Chronic stressors, during developmental sensitive periods and beyond, contribute to the risk of developing psychiatric conditions, including major depressive disorder (MDD). Epigenetic mechanisms including DNA methylation and histone modifications, at key stress response and neurotrophin genes, are increasingly implicated in mediating this risk. Although the exact mechanisms through which stressful environmental stimuli alter the epigenome are still unclear, research from the learning and memory fields indicates that epigenomic marks can be altered, at least in part, through calcium-dependent signaling cascades in direct response to neuronal activity. In this review, we highlight key findings from the stress, MDD, and learning and memory fields to propose a model where stress regulates downstream cellular functioning through activity-dependent epigenetic changes. Furthermore, we suggest that both typical and novel antidepressant treatments may exert positive influence through similar, activity-dependent pathways.

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Genetic Otx2 mis-localization delays critical period plasticity across brain regions

Cited by 71 publications

References 64 publications

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

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

Non-cell autonomous OTX2 transcription factor regulates anxiety-related behavior in the mouse

A role for activity‐dependent epigenetics in the development and treatment of major depressive disorder

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