{"id":{"repo_id":"mit","oai_identifier":"oai:dspace.mit.edu:1721.1/163552"},"canonical_url":"https://search.dev.ndltd.org/etd/mit/oai:dspace.mit.edu:1721.1/163552","repository":{"repo_id":"mit","name":"MIT","base_url":"https://dspace.mit.edu/oai/request"},"display":{"title":"Non-invasive tuning of experience-dependent plasticity in the primary visual cortex","abstract":"The cerebral cortex exhibits a remarkable capacity for experience-dependent plasticity, a feature that is predominantly confined to critical periods (CPs) during early postnatal development. In the mouse primary visual cortex (V1), ocular dominance plasticity (ODP) has served as a premier model for investigating the cellular and molecular mechanisms that underlie the formation and stabilization of cortical circuits. During the CP, short-term monocular deprivation (MD) induces both functional and anatomical changes in binocular V1, characterized by a weakening of deprived-eye responsiveness via mechanisms of synaptic long-term depression. As the critical period closes, increased inhibitory drive and the emergence of perineuronal nets (PNNs) stabilize neural circuits and restrict further experience-dependent plasticity. In Chapter 1, I review the key literature on ODP and provide a survey of interventions that have been shown to enhance ODP in adulthood. In Chapter 2, I present our findings that repeated anesthetic ketamine treatment can reinstate ‘juvenile-like’ plasticity in the adult mouse V1. Importantly, I demonstrate that this effect relies on the microglia-mediated depletion of PNNs, and that interfering with microglial purinergic P2Y12 receptor activation blocks the ketamine-induced enhancement of ODP. Building on these insights, Chapter 3 investigates the use of non-invasive light-flicker stimulation at different temporal frequencies as a means to unlock different forms of ODP in the adult mouse V1. Our results reveal that 60 Hz light-flicker stimulation reduces PNN levels and promotes a depression of deprived-eye responses following short-term MD, whereas 40 Hz stimulation – without altering PNN levels – enhances an adult form of ODP characterized by the strengthening of non-deprived eye responses following short-term MD. Furthermore, we show that in mice subjected to long-term MD initiated early in life, 40 Hz light-flicker treatment promotes recovery of visual function, as evidenced through physiological and behavioral assays. Finally, Chapter 4, outlines a series of future experiments designed to further elucidate the mechanisms by which light-flicker stimulation promotes enhanced ODP in adult V1. Together, the findings presented in this thesis introduce novel, minimally invasive (ketamine) and non-invasive (light-flicker) interventions that show promise as therapeutic strategies for ameliorating deficits arising from early life sensory deprivation.","abstract_html":"The cerebral cortex exhibits a remarkable capacity for experience-dependent plasticity, a feature that is predominantly confined to critical periods (CPs) during early postnatal development. In the mouse primary visual cortex (V1), ocular dominance plasticity (ODP) has served as a premier model for investigating the cellular and molecular mechanisms that underlie the formation and stabilization of cortical circuits. During the CP, short-term monocular deprivation (MD) induces both functional and anatomical changes in binocular V1, characterized by a weakening of deprived-eye responsiveness via mechanisms of synaptic long-term depression. As the critical period closes, increased inhibitory drive and the emergence of perineuronal nets (PNNs) stabilize neural circuits and restrict further experience-dependent plasticity. In Chapter 1, I review the key literature on ODP and provide a survey of interventions that have been shown to enhance ODP in adulthood. In Chapter 2, I present our findings that repeated anesthetic ketamine treatment can reinstate ‘juvenile-like’ plasticity in the adult mouse V1. Importantly, I demonstrate that this effect relies on the microglia-mediated depletion of PNNs, and that interfering with microglial purinergic P2Y12 receptor activation blocks the ketamine-induced enhancement of ODP. Building on these insights, Chapter 3 investigates the use of non-invasive light-flicker stimulation at different temporal frequencies as a means to unlock different forms of ODP in the adult mouse V1. Our results reveal that 60 Hz light-flicker stimulation reduces PNN levels and promotes a depression of deprived-eye responses following short-term MD, whereas 40 Hz stimulation – without altering PNN levels – enhances an adult form of ODP characterized by the strengthening of non-deprived eye responses following short-term MD. Furthermore, we show that in mice subjected to long-term MD initiated early in life, 40 Hz light-flicker treatment promotes recovery of visual function, as evidenced through physiological and behavioral assays. Finally, Chapter 4, outlines a series of future experiments designed to further elucidate the mechanisms by which light-flicker stimulation promotes enhanced ODP in adult V1. Together, the findings presented in this thesis introduce novel, minimally invasive (ketamine) and non-invasive (light-flicker) interventions that show promise as therapeutic strategies for ameliorating deficits arising from early life sensory deprivation.","abstract_has_math":false,"creators":["Reilly-Andújar, Francis"],"institution":"Massachusetts Institute of Technology","degree_name":"Doctoral","degree_level":null,"degree_discipline":null,"degree_department":"Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences","school":null,"contributors":[],"advisors":["Bear, Mark F."],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-05","date_published":"2025-05","updated_at":"2026-07-22T22:21:33Z","subjects":[],"languages":[],"rights":["In Copyright - Educational Use Permitted","Copyright retained by author(s)"],"rights_urls":["https://rightsstatements.org/page/InC-EDU/1.0/"],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/1721.1/163552","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Bear, Mark F."]},{"key":"dc:contributor.department","label":"Department","values":["Massachusetts Institute of Technology. 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In the mouse primary visual cortex (V1), ocular dominance plasticity (ODP) has served as a premier model for investigating the cellular and molecular mechanisms that underlie the formation and stabilization of cortical circuits. During the CP, short-term monocular deprivation (MD) induces both functional and anatomical changes in binocular V1, characterized by a weakening of deprived-eye responsiveness via mechanisms of synaptic long-term depression. As the critical period closes, increased inhibitory drive and the emergence of perineuronal nets (PNNs) stabilize neural circuits and restrict further experience-dependent plasticity. In Chapter 1, I review the key literature on ODP and provide a survey of interventions that have been shown to enhance ODP in adulthood. In Chapter 2, I present our findings that repeated anesthetic ketamine treatment can reinstate ‘juvenile-like’ plasticity in the adult mouse V1. Importantly, I demonstrate that this effect relies on the microglia-mediated depletion of PNNs, and that interfering with microglial purinergic P2Y12 receptor activation blocks the ketamine-induced enhancement of ODP. Building on these insights, Chapter 3 investigates the use of non-invasive light-flicker stimulation at different temporal frequencies as a means to unlock different forms of ODP in the adult mouse V1. Our results reveal that 60 Hz light-flicker stimulation reduces PNN levels and promotes a depression of deprived-eye responses following short-term MD, whereas 40 Hz stimulation – without altering PNN levels – enhances an adult form of ODP characterized by the strengthening of non-deprived eye responses following short-term MD. Furthermore, we show that in mice subjected to long-term MD initiated early in life, 40 Hz light-flicker treatment promotes recovery of visual function, as evidenced through physiological and behavioral assays. Finally, Chapter 4, outlines a series of future experiments designed to further elucidate the mechanisms by which light-flicker stimulation promotes enhanced ODP in adult V1. Together, the findings presented in this thesis introduce novel, minimally invasive (ketamine) and non-invasive (light-flicker) interventions that show promise as therapeutic strategies for ameliorating deficits arising from early life sensory deprivation."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Ph.D."]},{"key":"dc:title","label":"Title","values":["Non-invasive tuning of experience-dependent plasticity in the primary visual cortex"]}]}],"canonical_facts":{"dc:contributor.advisor":["Bear, Mark F."],"dc:contributor.department":["Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences"],"dc:creator":["Reilly-Andújar, Francis"],"dc:date.accessioned":["2025-11-05T19:34:08Z"],"dc:date.available":["2025-11-05T19:34:08Z"],"dc:date.issued":["2025-05"],"dc:description.abstract":["The cerebral cortex exhibits a remarkable capacity for experience-dependent plasticity, a feature that is predominantly confined to critical periods (CPs) during early postnatal development. In the mouse primary visual cortex (V1), ocular dominance plasticity (ODP) has served as a premier model for investigating the cellular and molecular mechanisms that underlie the formation and stabilization of cortical circuits. During the CP, short-term monocular deprivation (MD) induces both functional and anatomical changes in binocular V1, characterized by a weakening of deprived-eye responsiveness via mechanisms of synaptic long-term depression. As the critical period closes, increased inhibitory drive and the emergence of perineuronal nets (PNNs) stabilize neural circuits and restrict further experience-dependent plasticity. In Chapter 1, I review the key literature on ODP and provide a survey of interventions that have been shown to enhance ODP in adulthood. In Chapter 2, I present our findings that repeated anesthetic ketamine treatment can reinstate ‘juvenile-like’ plasticity in the adult mouse V1. Importantly, I demonstrate that this effect relies on the microglia-mediated depletion of PNNs, and that interfering with microglial purinergic P2Y12 receptor activation blocks the ketamine-induced enhancement of ODP. Building on these insights, Chapter 3 investigates the use of non-invasive light-flicker stimulation at different temporal frequencies as a means to unlock different forms of ODP in the adult mouse V1. Our results reveal that 60 Hz light-flicker stimulation reduces PNN levels and promotes a depression of deprived-eye responses following short-term MD, whereas 40 Hz stimulation – without altering PNN levels – enhances an adult form of ODP characterized by the strengthening of non-deprived eye responses following short-term MD. Furthermore, we show that in mice subjected to long-term MD initiated early in life, 40 Hz light-flicker treatment promotes recovery of visual function, as evidenced through physiological and behavioral assays. Finally, Chapter 4, outlines a series of future experiments designed to further elucidate the mechanisms by which light-flicker stimulation promotes enhanced ODP in adult V1. Together, the findings presented in this thesis introduce novel, minimally invasive (ketamine) and non-invasive (light-flicker) interventions that show promise as therapeutic strategies for ameliorating deficits arising from early life sensory deprivation."],"dc:description.degree":["Ph.D."],"dc:identifier.uri":["https://hdl.handle.net/1721.1/163552"],"dc:publisher":["Massachusetts Institute of Technology"],"dc:rights":["In Copyright - Educational Use Permitted","Copyright retained by author(s)"],"dc:rights.uri":["https://rightsstatements.org/page/InC-EDU/1.0/"],"dc:title":["Non-invasive tuning of experience-dependent plasticity in the primary visual cortex"],"dc:type":["Thesis"],"thesis:degree_name":["Doctoral","Doctor of Philosophy"]},"updated_at":"2026-07-22T22:21:33Z"}