The BCM theory of synapse modification at 30: interaction of theory with experiment

Cooper, Leon N.; Bear, Mark F.

doi:10.1038/nrn3353

Cited by 335 publications

(418 citation statements)

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“…According to the BCM theory, the modification threshold of plasticity needs to be lowered before any potentiation can occur, implying that Dc-ODP must occur before Pc-ODP (Cooper and Bear, 2012). However, in SRF-dn and MEF2-dn animals, we see Pc-ODP even without Dc-ODP.…”

Section: Discussionmentioning

confidence: 91%

The Role of CREB, SRF, and MEF2 in Activity-Dependent Neuronal Plasticity in the Visual Cortex

et al. 2017

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The transcription factors CREB (cAMP response element binding factor), SRF (serum response factor), and MEF2 (myocyte enhancer factor 2) play critical roles in the mechanisms underlying neuronal plasticity. However, the role of the activation of these transcription factors in the different components of plasticity in vivo is not well known. In this study, we tested the role of CREB, SRF, and MEF2 in ocular dominance plasticity (ODP), a paradigm of activity-dependent neuronal plasticity in the visual cortex. These three proteins bind to the synaptic activity response element (SARE), an enhancer sequence found upstream of many plasticity-related genes (

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Section: Discussionmentioning

confidence: 91%

The Role of CREB, SRF, and MEF2 in Activity-Dependent Neuronal Plasticity in the Visual Cortex

et al. 2017

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“…A better understanding of what allows recovery with patching might suggest improvements over the current standard of care. One view is that recovery is enabled by a reduction in cortical activity that occurs when the strong eye is occluded (27). Support for this idea comes from findings that exposure of rats (28) and kittens (30,32) to complete darkness for 10-14 d can promote recovery from the effects of MD when visual experience is restored.…”

Section: Discussionmentioning

confidence: 99%

“…After a period of attenuated cortical activity, the threshold for synaptic potentiation is reduced (24-26). Thus, the period of quiescence that immediately follows initiation of reverse occlusion lowers the threshold for synaptic potentiation, enabling subsequent visual experience to increase synaptic effectiveness when it would have otherwise been without effect (27). An intriguing possibility is that imposition of a period of binocular inactivity following early MD could be sufficient to promote visual recovery without forcing the eyes to compete.…”

mentioning

confidence: 99%

Rapid recovery from the effects of early monocular deprivation is enabled by temporary inactivation of the retinas

Fong

Mitchell

Duffy

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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A half-century of research on the consequences of monocular deprivation (MD) in animals has revealed a great deal about the pathophysiology of amblyopia. MD initiates synaptic changes in the visual cortex that reduce acuity and binocular vision by causing neurons to lose responsiveness to the deprived eye. However, much less is known about how deprivation-induced synaptic modifications can be reversed to restore normal visual function. One theoretically motivated hypothesis is that a period of inactivity can reduce the threshold for synaptic potentiation such that subsequent visual experience promotes synaptic strengthening and increased responsiveness in the visual cortex. Here we have reduced this idea to practice in two species. In young mice, we show that the otherwise stable loss of cortical responsiveness caused by MD is reversed when binocular visual experience follows temporary anesthetic inactivation of the retinas. In 3-mo-old kittens, we show that a severe impairment of visual acuity is also fully reversed by binocular experience following treatment and, further, that prolonged retinal inactivation alone can erase anatomical consequences of MD. We conclude that temporary retinal inactivation represents a highly efficacious means to promote recovery of function. A mblyopia is a widespread form of human visual disability that arises from imbalanced visual experience in the two eyes during infancy or early childhood. The core pathophysiological process underlying amblyopia is ocular dominance plasticity in the primary visual cortex (V1). Ocular dominance plasticity, evolutionarily conserved in mammals with binocular vision, has become a classic paradigm for studying how brain development is influenced by experience and deprivation. A brief period of monocular deprivation (MD) during early postnatal life causes functional depression of synapses in V1 that serve the deprived eye (1-7). Consequently, early-life MD severely and persistently degrades visual acuity through the deprived eye, which typically fails to recover spontaneously when binocular vision is restored (8-10). A critical step in developing targeted interventions for treating amblyopia is to identify strategies for reversing deprivation-driven synaptic modifications in V1.The traditional approach to promote recovery following MD has been to occlude the strong eye to force vision through the weak amblyopic eye. This "reverse occlusion" approach has been validated in animals (11, 12) and represents the cornerstone of current treatment (patching therapy) of human amblyopia (13-16). However, this treatment has well-known limitations that include poor compliance, potential loss of vision through the newly patched eye, failure to recover binocular vision, and a declining treatment efficacy with age (15, 17-21). Nevertheless, the success of reverse occlusion strategies demonstrates that severely weakened synaptic inputs in the brain can be rejuvenated under appropriate circumstances.An insight into how reverse occlusion might promote recovery came fr...

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“…Based on the BCM -Bienenstock, Cooper, and Munro -and metaplasticity theories, it can be mentioned that the effects of long-term potentiation (LTP) and long-term depression (LTD) are limited and after a certain number of interventions no further neuroplastic changes are expected [46,47]. With neurostimulation, hyperactive neurons reduce input by increasing their thresholds (LTP to LTD) while hypoactive neurons do the opposite (LTD to LTP) [47].…”

Section: (Iii) When Do Missed Neurostimulation Visits Bias Final Resumentioning

confidence: 99%

“…With neurostimulation, hyperactive neurons reduce input by increasing their thresholds (LTP to LTD) while hypoactive neurons do the opposite (LTD to LTP) [47]. This parallels pharmacologic dosing, and drug half-lives, and is a window into understanding dosing mechanisms in NIBS.…”

Section: (Iii) When Do Missed Neurostimulation Visits Bias Final Resumentioning

confidence: 99%

Strategies for replacing non-invasive brain stimulation sessions: recommendations for designing neurostimulation clinical trials

Thibaut

O’Brien

Fregni

2017

Expert Review of Medical Devices

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Introduction: Despite the potential impact of missed visits on the outcomes of neuromodulation treatments, it is not clear how this issue has been addressed in clinical trials. Given this gap in the literature, we reviewed articles on non-invasive brain stimulation in participants with depression or chronic pain, and investigated how missed visits were handled. Areas covered:We performed a search on PUBMED/MEDLINE using the keywords: "tDCS", "transcranial direct current stimulation", "transcranial magnetic stimulation¨, "depression", and "pain". We included studies with a minimum of five participants who were diagnosed with depression or chronic pain, who underwent a minimum of five tDCS or TMS sessions. A total of 181 studies matched our inclusion criteria, 112 on depression and 69 on chronic pain. Of these, only fifteen (8%) articles reported or had a protocol addressing missed visits. This review demonstrates that, in most of the trials, there is no reported plan to handle missed visits.Expert commentary: Based on our findings and previous studies, we developed suggestions on how to handle missed visits in neuromodulation protocols. A maximum of 20% of missing sessions should be allowed before excluding a patient and these sessions should be replaced at the end of the stimulation period.

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The BCM theory of synapse modification at 30: interaction of theory with experiment

Cited by 335 publications

References 185 publications

The Role of CREB, SRF, and MEF2 in Activity-Dependent Neuronal Plasticity in the Visual Cortex

The Role of CREB, SRF, and MEF2 in Activity-Dependent Neuronal Plasticity in the Visual Cortex

Rapid recovery from the effects of early monocular deprivation is enabled by temporary inactivation of the retinas

Strategies for replacing non-invasive brain stimulation sessions: recommendations for designing neurostimulation clinical trials

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