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Regulating critical period plasticity: insight from the visual system to fear circuitry for therapeutic interventions.

Nabel EM, Morishita H - Front Psychiatry (2013)

Bottom Line: A major molecular brake in the visual cortex, perineuronal net formation, recently has been identified in the development of fear systems that are resilient to fear memory erasure.The roles of other molecular brakes, myelin-related Nogo receptor signaling and Lynx family proteins - endogenous inhibitors for nicotinic acetylcholine receptor, are explored in the context of fear memory plasticity.Such fear plasticity regulators, including epigenetic effects, provide promising targets for therapeutic interventions.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai , New York, NY , USA.

ABSTRACT
Early temporary windows of heightened brain plasticity called critical periods developmentally sculpt neural circuits and contribute to adult behavior. Regulatory mechanisms of visual cortex development - the preeminent model of experience-dependent critical period plasticity-actively limit adult plasticity and have proved fruitful therapeutic targets to reopen plasticity and rewire faulty visual system connections later in life. Interestingly, these molecular mechanisms have been implicated in the regulation of plasticity in other functions beyond vision. Applying mechanistic understandings of critical period plasticity in the visual cortex to fear circuitry may provide a conceptual framework for developing novel therapeutic tools to mitigate aberrant fear responses in post traumatic stress disorder. In this review, we turn to the model of experience-dependent visual plasticity to provide novel insights for the mechanisms regulating plasticity in the fear system. Fear circuitry, particularly fear memory erasure, also undergoes age-related changes in experience-dependent plasticity. We consider the contributions of molecular brakes that halt visual critical period plasticity to circuitry underlying fear memory erasure. A major molecular brake in the visual cortex, perineuronal net formation, recently has been identified in the development of fear systems that are resilient to fear memory erasure. The roles of other molecular brakes, myelin-related Nogo receptor signaling and Lynx family proteins - endogenous inhibitors for nicotinic acetylcholine receptor, are explored in the context of fear memory plasticity. Such fear plasticity regulators, including epigenetic effects, provide promising targets for therapeutic interventions.

No MeSH data available.


Related in: MedlinePlus

Critical Period for experience-dependent plasticity in visual and fear system. (A) Critical period of visual cortex plasticity: visual cortex development is the preeminent model for the study of critical period plasticity and its regulators. Visually depriving one eye by obstructing it early in life yields a life-long loss of visual acuity (amblyopia). Studies of mouse visual cortex development, which has a well-defined 2 weeks critical period that peaks at 1 month after birth, have identified several endogenous “molecular brakes” (colored in red) that close the critical period. These include perineuronal nets (PNNs), myelin-related Nogo receptor (NgR) and PirB, and a nicotinic brake Lynx1. (B) Critical period of fear erasure: a critical period for the fear system near adolescence is emerging through current research. In rodents, extinction can permanently erase fear memory during a preadolescent critical period around 17 days after birth, however, extinction at 24 days or later fails to bar fear memories from re-emerging. Increased PNNs in the amygdala and maturation of input from medial prefrontal cortex (mPFC) to amygdala contribute to the closure of this critical period. Nogo receptor (NgR: colored in light red) also limits fear extinction, but its contribution on fear erasure is not tested. (C) Interventions for enhancing visual cortex plasticity in the adult: counteracting molecular brakes through pharmacological (ChABC, SSRI, HDACI, AChEI: colored in green) and behavioral (environmental enrichment, dark exposure) approaches is a promising therapeutic strategic for recovery from amblyopia. (D) Interventions for fear erasure in the adult: juvenile-like plasticity can be reintroduced in adulthood through pharmacological treatment (ChABC, SSRI treatment) or reconsolidation update. HDACI administration (colored in light green) enhances extinction, but its effect on fear erasure has not been examined yet.
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Figure 1: Critical Period for experience-dependent plasticity in visual and fear system. (A) Critical period of visual cortex plasticity: visual cortex development is the preeminent model for the study of critical period plasticity and its regulators. Visually depriving one eye by obstructing it early in life yields a life-long loss of visual acuity (amblyopia). Studies of mouse visual cortex development, which has a well-defined 2 weeks critical period that peaks at 1 month after birth, have identified several endogenous “molecular brakes” (colored in red) that close the critical period. These include perineuronal nets (PNNs), myelin-related Nogo receptor (NgR) and PirB, and a nicotinic brake Lynx1. (B) Critical period of fear erasure: a critical period for the fear system near adolescence is emerging through current research. In rodents, extinction can permanently erase fear memory during a preadolescent critical period around 17 days after birth, however, extinction at 24 days or later fails to bar fear memories from re-emerging. Increased PNNs in the amygdala and maturation of input from medial prefrontal cortex (mPFC) to amygdala contribute to the closure of this critical period. Nogo receptor (NgR: colored in light red) also limits fear extinction, but its contribution on fear erasure is not tested. (C) Interventions for enhancing visual cortex plasticity in the adult: counteracting molecular brakes through pharmacological (ChABC, SSRI, HDACI, AChEI: colored in green) and behavioral (environmental enrichment, dark exposure) approaches is a promising therapeutic strategic for recovery from amblyopia. (D) Interventions for fear erasure in the adult: juvenile-like plasticity can be reintroduced in adulthood through pharmacological treatment (ChABC, SSRI treatment) or reconsolidation update. HDACI administration (colored in light green) enhances extinction, but its effect on fear erasure has not been examined yet.

Mentions: The visual system offers valuable insight through the study of critical period mechanisms. In humans and animals, visually depriving one eye by obstructing it early in life yields loss in visual acuity (amblyopia) by stimulating an anatomical remodeling within primary visual cortex (3). Importantly, such an effect of visual deprivation has not been seen in the adult, strongly suggesting the presence of a developmental critical period for visual experience-dependent plasticity in visual cortex. Due to a lack of sufficient brain plasticity in adulthood, untreated monocular deprivation during childhood results in life-long amblyopia, a condition affecting 2–5% of the human population (4). Indeed, recovery from deprivation amblyopia in adulthood is limited across species, from higher mammals (3), to rodents (5, 6), and requires therapeutic intervention. Over the last 10 years, the murine visual system, has emerged as a valuable model system for creating such intervention, having a well-defined, 2 week critical period that peaks 1 month after birth (Figure 1A). The predictability and duration of this temporal window is particularly useful for dissecting the molecular mechanisms of visual cortex plasticity through genetic manipulation and environmental intervention (7). Critical period mechanisms identified in rodent visual cortex have not only catalyzed multiple pharmacological and behavioral interventions that aid functional recovery in adults (8), but have also guided research uncovering molecular mechanisms of critical period plasticity in other brain regions, especially the auditory and fear systems (9–11).


Regulating critical period plasticity: insight from the visual system to fear circuitry for therapeutic interventions.

Nabel EM, Morishita H - Front Psychiatry (2013)

Critical Period for experience-dependent plasticity in visual and fear system. (A) Critical period of visual cortex plasticity: visual cortex development is the preeminent model for the study of critical period plasticity and its regulators. Visually depriving one eye by obstructing it early in life yields a life-long loss of visual acuity (amblyopia). Studies of mouse visual cortex development, which has a well-defined 2 weeks critical period that peaks at 1 month after birth, have identified several endogenous “molecular brakes” (colored in red) that close the critical period. These include perineuronal nets (PNNs), myelin-related Nogo receptor (NgR) and PirB, and a nicotinic brake Lynx1. (B) Critical period of fear erasure: a critical period for the fear system near adolescence is emerging through current research. In rodents, extinction can permanently erase fear memory during a preadolescent critical period around 17 days after birth, however, extinction at 24 days or later fails to bar fear memories from re-emerging. Increased PNNs in the amygdala and maturation of input from medial prefrontal cortex (mPFC) to amygdala contribute to the closure of this critical period. Nogo receptor (NgR: colored in light red) also limits fear extinction, but its contribution on fear erasure is not tested. (C) Interventions for enhancing visual cortex plasticity in the adult: counteracting molecular brakes through pharmacological (ChABC, SSRI, HDACI, AChEI: colored in green) and behavioral (environmental enrichment, dark exposure) approaches is a promising therapeutic strategic for recovery from amblyopia. (D) Interventions for fear erasure in the adult: juvenile-like plasticity can be reintroduced in adulthood through pharmacological treatment (ChABC, SSRI treatment) or reconsolidation update. HDACI administration (colored in light green) enhances extinction, but its effect on fear erasure has not been examined yet.
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Related In: Results  -  Collection

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Figure 1: Critical Period for experience-dependent plasticity in visual and fear system. (A) Critical period of visual cortex plasticity: visual cortex development is the preeminent model for the study of critical period plasticity and its regulators. Visually depriving one eye by obstructing it early in life yields a life-long loss of visual acuity (amblyopia). Studies of mouse visual cortex development, which has a well-defined 2 weeks critical period that peaks at 1 month after birth, have identified several endogenous “molecular brakes” (colored in red) that close the critical period. These include perineuronal nets (PNNs), myelin-related Nogo receptor (NgR) and PirB, and a nicotinic brake Lynx1. (B) Critical period of fear erasure: a critical period for the fear system near adolescence is emerging through current research. In rodents, extinction can permanently erase fear memory during a preadolescent critical period around 17 days after birth, however, extinction at 24 days or later fails to bar fear memories from re-emerging. Increased PNNs in the amygdala and maturation of input from medial prefrontal cortex (mPFC) to amygdala contribute to the closure of this critical period. Nogo receptor (NgR: colored in light red) also limits fear extinction, but its contribution on fear erasure is not tested. (C) Interventions for enhancing visual cortex plasticity in the adult: counteracting molecular brakes through pharmacological (ChABC, SSRI, HDACI, AChEI: colored in green) and behavioral (environmental enrichment, dark exposure) approaches is a promising therapeutic strategic for recovery from amblyopia. (D) Interventions for fear erasure in the adult: juvenile-like plasticity can be reintroduced in adulthood through pharmacological treatment (ChABC, SSRI treatment) or reconsolidation update. HDACI administration (colored in light green) enhances extinction, but its effect on fear erasure has not been examined yet.
Mentions: The visual system offers valuable insight through the study of critical period mechanisms. In humans and animals, visually depriving one eye by obstructing it early in life yields loss in visual acuity (amblyopia) by stimulating an anatomical remodeling within primary visual cortex (3). Importantly, such an effect of visual deprivation has not been seen in the adult, strongly suggesting the presence of a developmental critical period for visual experience-dependent plasticity in visual cortex. Due to a lack of sufficient brain plasticity in adulthood, untreated monocular deprivation during childhood results in life-long amblyopia, a condition affecting 2–5% of the human population (4). Indeed, recovery from deprivation amblyopia in adulthood is limited across species, from higher mammals (3), to rodents (5, 6), and requires therapeutic intervention. Over the last 10 years, the murine visual system, has emerged as a valuable model system for creating such intervention, having a well-defined, 2 week critical period that peaks 1 month after birth (Figure 1A). The predictability and duration of this temporal window is particularly useful for dissecting the molecular mechanisms of visual cortex plasticity through genetic manipulation and environmental intervention (7). Critical period mechanisms identified in rodent visual cortex have not only catalyzed multiple pharmacological and behavioral interventions that aid functional recovery in adults (8), but have also guided research uncovering molecular mechanisms of critical period plasticity in other brain regions, especially the auditory and fear systems (9–11).

Bottom Line: A major molecular brake in the visual cortex, perineuronal net formation, recently has been identified in the development of fear systems that are resilient to fear memory erasure.The roles of other molecular brakes, myelin-related Nogo receptor signaling and Lynx family proteins - endogenous inhibitors for nicotinic acetylcholine receptor, are explored in the context of fear memory plasticity.Such fear plasticity regulators, including epigenetic effects, provide promising targets for therapeutic interventions.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai , New York, NY , USA.

ABSTRACT
Early temporary windows of heightened brain plasticity called critical periods developmentally sculpt neural circuits and contribute to adult behavior. Regulatory mechanisms of visual cortex development - the preeminent model of experience-dependent critical period plasticity-actively limit adult plasticity and have proved fruitful therapeutic targets to reopen plasticity and rewire faulty visual system connections later in life. Interestingly, these molecular mechanisms have been implicated in the regulation of plasticity in other functions beyond vision. Applying mechanistic understandings of critical period plasticity in the visual cortex to fear circuitry may provide a conceptual framework for developing novel therapeutic tools to mitigate aberrant fear responses in post traumatic stress disorder. In this review, we turn to the model of experience-dependent visual plasticity to provide novel insights for the mechanisms regulating plasticity in the fear system. Fear circuitry, particularly fear memory erasure, also undergoes age-related changes in experience-dependent plasticity. We consider the contributions of molecular brakes that halt visual critical period plasticity to circuitry underlying fear memory erasure. A major molecular brake in the visual cortex, perineuronal net formation, recently has been identified in the development of fear systems that are resilient to fear memory erasure. The roles of other molecular brakes, myelin-related Nogo receptor signaling and Lynx family proteins - endogenous inhibitors for nicotinic acetylcholine receptor, are explored in the context of fear memory plasticity. Such fear plasticity regulators, including epigenetic effects, provide promising targets for therapeutic interventions.

No MeSH data available.


Related in: MedlinePlus