Neuromodulators Control the Polarity of Spike-Timing-Dependent Synaptic Plasticity

Seol, Geun Hee; Žiburkus, Jokūbas; Huang, Shiyong; Lee, Song; Kim, In Tae; Takamiya, Kogo; Huganir, Richard L.; Lee, Hey Kyoung; Kirkwood, Alfredo

doi:10.1016/j.neuron.2007.11.007

Cited by 67 publications

(115 citation statements)

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“…4 A and B). Com- parably low rates of successful LTP induction are commonly seen with similar LTP protocols in this pathway (18)(19)(20). In striking contrast, LTP was enhanced in H-ras G12V mice, with 60% of neurons showing significant potentiation and a mean potentiation magnitude of 1.56 ± 0.13.…”

Section: Resultsmentioning

confidence: 97%

Constitutively active H-ras accelerates multiple forms of plasticity in developing visual cortex

Kaneko

Cheetham

Lee

et al. 2010

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

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Experience-dependent cortical plasticity has been studied by using loss-of-function methods. Here, we take the complementary approach of using a genetic gain-of-function that enhances plasticity. We show that a constitutively active form of H-ras (H-ras G12V ), expressed presynaptically at excitatory synapses in mice, accelerates and enhances multiple, mechanistically distinct forms of plasticity in the developing visual cortex. In vivo, H-ras G12V not only increased the rate of ocular dominance change in response to monocular deprivation (MD), but also accelerated recovery from deprivation by reverse occlusion. In vitro, H-ras G12V expression decreased baseline presynaptic release probability and enhanced presynaptically expressed longterm potentiation (LTP). H-ras G12V expression also accelerated the increase following MD in the frequency of miniature excitatory potentials, mirroring accelerated plasticity in vivo. These findings demonstrate accelerated neocortical plasticity, which offers an avenue toward future therapies for many neurological and neuropsychiatric disorders.gain of function | monocular deprivation | mouse | ocular dominance | presynaptic long-term potentiation

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Section: Resultsmentioning

confidence: 97%

Constitutively active H-ras accelerates multiple forms of plasticity in developing visual cortex

Kaneko

Cheetham

Lee

et al. 2010

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

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“…Because it is well established that neuromodulators are essential for experience dependent plasticity in cortex (39,40), and that they regulate synaptic plasticity in cortical slices (41,42), they are natural candidates for our reward signals. It is often assumed that dopamine is responsible for implementing rewards (43), and it is known to modulate the perception of time (2) in both human (5,44) and non-human (45) subjects.…”

Section: Discussionmentioning

confidence: 99%

Learning reward timing in cortex through reward dependent expression of synaptic plasticity

Gavornik

Shuler

Loewenstein

et al. 2009

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

124

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The ability to represent time is an essential component of cognition but its neural basis is unknown. Although extensively studied both behaviorally and electrophysiologically, a general theoretical framework describing the elementary neural mechanisms used by the brain to learn temporal representations is lacking. It is commonly believed that the underlying cellular mechanisms reside in high order cortical regions but recent studies show sustained neural activity in primary sensory cortices that can represent the timing of expected reward. Here, we show that local cortical networks can learn temporal representations through a simple framework predicated on reward dependent expression of synaptic plasticity. We assert that temporal representations are stored in the lateral synaptic connections between neurons and demonstrate that reward-modulated plasticity is sufficient to learn these representations. We implement our model numerically to explain reward-time learning in the primary visual cortex (V1), demonstrate experimental support, and suggest additional experimentally verifiable predictions. reinforcment learning ͉ visual cortex O ur brains process time with such instinctual ease that the difficulty of defining what time is, in a neural sense, seems paradoxical. There is a rich literature in experimental neuroscience describing the temporal dynamics of both cellular and system-level neuronal processes and many insightful psychophysical studies have revealed perceptual correlates of time. Despite this, and the clear importance of accurate temporal processing at all levels of behavior, we still know little about how time is represented or used by the brain (1). Temporal processing is classically understood as a higher order function, and although there is some disagreement (2, 3), it is often argued that dedicated structures or regions in the brain are responsible for representing time (4). Because different mechanisms are likely responsible for computing timing at different time scales (1,5,6), and because there is evidence for modality specific temporal mechanisms (7), an alternative possibility is that timing processes develop locally within different brain regions.Recent evidence indicates that temporal representations are expressed in primary sensory cortices (8-10) and that rewardbased reinforcement can affect the form of stimulus driven activity in the primary somatosensory cortex (11-13). In particular, Shuler and Bear (9) showed that neurons in rat primary visual cortex can develop persistent activity, evoked by brief visual stimuli, that robustly represents the temporal interval between a visual stimulus and paired reward (Fig. 1). A mechanistic framework capable of describing how a neural substrate can learn the observed temporal representations does not exist.Here, we explain how these temporal signals can be encoded in recurrent excitatory synaptic connections and how a local network can learn specific temporal instantiations through reward modulated plasticity. Although our model is potentially ...

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“…In addition to changes in molecular signaling pathways, VNS induces changes in synaptic and intrinsic neuronal properties that may support recovery. VNS-dependent release of acetylcholine and norepinephrine may act together to alter spike-timing dependent plasticity properties to facilitate plasticity in active networks [148,149]. Moreover, VNS may directly alter synaptic properties by regulating expression of Nmethyl-D-aspartate receptor and γ-aminobutyric acid receptor A [150].…”

Section: Identifying Mechanisms That Underlie Recoverymentioning

confidence: 99%

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

Hays

2016

Neurotherapeutics

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Pathological neural activity could be treated by directing specific plasticity to renormalize circuits and restore function. Rehabilitative therapies aim to promote adaptive circuit changes after neurological disease or injury, but insufficient or maladaptive plasticity often prevents a full recovery. The development of adjunctive strategies that broadly support plasticity to facilitate the benefits of rehabilitative interventions has the potential to improve treatment of a wide range of neurological disorders. Recently, stimulation of the vagus nerve in conjunction with rehabilitation has emerged as one such potential targeted plasticity therapy. Vagus nerve stimulation (VNS) drives activation of neuromodulatory nuclei that are associated with plasticity, including the cholinergic basal forebrain and the noradrenergic locus coeruleus. Repeatedly pairing brief bursts of VNS sensory or motor events drives robust, event-specific plasticity in neural circuits. Animal models of chronic tinnitus, ischemic stroke, intracerebral hemorrhage, traumatic brain injury, and post-traumatic stress disorder benefit from delivery of VNS paired with successful trials during rehabilitative training. Moreover, mounting evidence from pilot clinical trials provides an initial indication that VNS-based targeted plasticity therapies may be effective in patients with neurological diseases and injuries. Here, I provide a discussion of the current uses and potential future applications of VNS-based targeted plasticity therapies in animal models and patients, and outline challenges for clinical implementation.

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Neuromodulators Control the Polarity of Spike-Timing-Dependent Synaptic Plasticity

Cited by 67 publications

References 0 publications

Constitutively active H-ras accelerates multiple forms of plasticity in developing visual cortex

Constitutively active H-ras accelerates multiple forms of plasticity in developing visual cortex

Learning reward timing in cortex through reward dependent expression of synaptic plasticity

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

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