Removing brakes on adult brain plasticity: From molecular to behavioral interventions
Open accessAbstract
Adult brain plasticity, although possible, remains more restricted in scope than during development. Here, we address conditions under which circuit rewiring may be facilitated in the mature brain. At a cellular and molecular level, adult plasticity is actively limited. Some of these “brakes” are structural, such as perineuronal nets or myelin, which inhibit neurite outgrowth. Others are functional, acting directly upon excitatory-inhibitory balance within local circuits. Plasticity in adulthood can be induced either by lifting these brakes through invasive interventions or by exploiting endogenous permissive factors, such as neuromodulators. Using the amblyopic visual system as a model, we discuss genetic, pharmacological, and environmental removal of brakes to enable recovery of vision in adult rodents. Although these mechanisms remain largely uncharted in the human, we consider how they may provide a biological foundation for the remarkable increase in plasticity after action video game play by amblyopic subjects.
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The balance between plasticity and stability is tilted toward plasticity early in life, and at maturity it shifts toward greater stability of neural circuits, although restricted plasticity remains.
“The balance between plasticity and stability is tilted towards plasticity early in life -- a time when there are many opportunities for the brain to be sculpted by experiences – ranging from initial sensory experiences to early nutrient exposure/restriction or developmental adversities (70; 71; 72). At maturity, the balance is shifted toward greater stability of neural circuits, although the”
From Adolescent Neurodevelopment (2013) · cites this paper as [72]
Typical antidepressants may promote a neuroplastic state resembling the highly malleable brain of early development, potentially allowing changes in brain structure and function that are otherwise limited in the adult brain.
“Typical antidepressants may promote a neuroplastic state similar to the highly malleable brain in early development, possibly allowing for changes in brain structure and function that are otherwise limited in the adult brain, which is relatively more stable, as previously reviewed [84-86].”
From Beyond the serotonin deficit hypothesis: Communicating a neuroplasticity framework of major depressive disorder (2024) · cites this paper as [85]
Various drugs, environmental manipulations, and genetic approaches have induced iPlasticity across several model systems and in people.
“Subsequently, several pharmacological treatments (Table 1) and environmental manipulations7,191–193, as well as genetic means, have been used to induce iPlasticity in several model systems and also in humans186.”
From Neuronal plasticity and neurotrophic factors in drug responses (2017) · cites this paper as [186]
Shifting the excitatory-inhibitory balance in relevant neural circuits may increase plasticity.
“Evidence from a promising line of studies suggests that shifting the excitatory-inhibitory balance in relevant neural circuits may increase plasticity (Thompson et al., 2008, Bavelier et al., 2010).”
From The impact of developmental timing for stress and recovery (2015) · cites this paper as Bavelier et al., 2010
Mature PNNs are inhibitory for experience-dependent plasticity; their increase correlates with critical period termination and removal in adult V1 restores plasticity.
“Mature PNN is inhibitory for experience-dependent plasticity: its increase in developing V1 correlates with the termination of the critical period and its removal in adult V1 restores plasticity (27,31,32).”
From MeCP2 regulates the timing of critical period plasticity that shapes functional connectivity in primary visual cortex (2015) · cites this paper as [32]
Pathophysiological changes are consistent with dematuration or removal of brakes on plasticity.
“Pathophysiological changes (1–3) are consistent with ‘dematuration’ or a removal of ‘brakes’ on plasticity (72, 73).”
From Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons (2015) · cites this paper as [72]
In adult wild-type mice older than P90, 4-day short-term monocular deprivation does not impair vision.
“In adult (>P90) wild-type mice, a short-term monocular deprivation (STMD; 4 days) fails to impair vision (Bavelier et al., 2010; Prusky and Douglas, 2003).”
From Choroid-Plexus-Derived Otx2 Homeoprotein Constrains Adult Cortical Plasticity (2013) · cites this paper as Bavelier et al., 2010
Experience-dependent plasticity occurs in adulthood, and mammalian neuronal circuits can change in response to new experience throughout life.
“Cumulative data have shown that experience-dependent plasticity occurs in adulthood and it is now well accepted that neuronal circuits of the mammalian brain are capable of changing in response to new experience throughout life [7–11].”
From Experience-dependent structural plasticity in the cortex (2011) · cites this paper as [9]
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“However, several environmental or pharmacological interventions reactivate iPlasticity in the adult brain [79].”
BackgroundFluoxetine treatment promotes functional recovery in a rat model of cervical spinal cord injury
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- Authors
- Bavelier, D., Levi, D. M., Li, R. W., Dan, Y., & Hensch, T. K.
- Affiliations
- University of Rochester (US)
- Howard Hughes Medical Institute (US)
- Boston Children's Hospital (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-11-10
- Volume
- 30
- Issue
- 45
- Pages
- 14964-14971
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2992973
- OpenAlex
- W1988993555
- Cited by
- 589
- References
- 131
- Citations by year
- 2026: 30 · 2025: 21 · 2024: 25 · 2023: 24 · 2022: 24 · 2021: 35 · 2020: 40 · 2019: 30 · 2018: 32 · 2017: 47 · 2016: 53 · 2015: 59 · 2014: 45 · 2013: 52 · 2012: 49
- FWCI
- 12.54
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- Ellison Medical Foundation
- James S. McDonnell Foundation
- U.S. Public Health Service (EYRO10178)
- National Eye Institute (EY-016880, R01EY020976, R01EY018861, EY18861, R01EY016880, R01EY001728)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Visual perception and processing mechanisms
- Keywords
- adult brain plasticity, perineuronal nets, myelin, neurite outgrowth, excitation-inhibition balance, neuromodulators, amblyopia, pharmacological interventions, action video games
- MeSH terms
- Animals, Brain, Critical Period, Psychological, Humans, Neuronal Plasticity, Neurons, Synapses
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