Article

Reversing pathological neural activity using targeted plasticity

Cortical Plasticity Laboratory, Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, Texas 75080, USA.
Nature (Impact Factor: 41.46). 02/2011; 470(7332):101-4. DOI: 10.1038/nature09656
Source: PubMed

ABSTRACT

Brain changes in response to nerve damage or cochlear trauma can generate pathological neural activity that is believed to be responsible for many types of chronic pain and tinnitus. Several studies have reported that the severity of chronic pain and tinnitus is correlated with the degree of map reorganization in somatosensory and auditory cortex, respectively. Direct electrical or transcranial magnetic stimulation of sensory cortex can temporarily disrupt these phantom sensations. However, there is as yet no direct evidence for a causal role of plasticity in the generation of pain or tinnitus. Here we report evidence that reversing the brain changes responsible can eliminate the perceptual impairment in an animal model of noise-induced tinnitus. Exposure to intense noise degrades the frequency tuning of auditory cortex neurons and increases cortical synchronization. Repeatedly pairing tones with brief pulses of vagus nerve stimulation completely eliminated the physiological and behavioural correlates of tinnitus in noise-exposed rats. These improvements persisted for weeks after the end of therapy. This method for restoring neural activity to normal may be applicable to a variety of neurological disorders.

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    • "Further work is needed to characterize this cardio-excitatory reflex and also investigate potential effects on the efficacy of VNS therapies. Among myriad potential therapies currently under investigation (Kirchner et al. 2000;Groves and Brown 2005;De Ferrari et al. 2011;Engineer et al. 2011), the recent use of VNS for improving long-term morbidity in patients with heart failure has generated significant interest among clinicians and researchers (Schwartz and De Ferrari 2009;De Ferrari et al. 2011;Sabbah et al. 2011;Premchand et al. 2014;Zannad et al. 2015). However, the precise role of VNS-evoked bradycardia in the treatment of heart failure remains unclear. "
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    Preview · Article · Feb 2016
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    • "Similarly, noradrenaline and serotonin play a permissive and facilitatory role for the induction of plasticity (Seidenbacher et al., 1997;Gu, 2002; Tully and Bolshakov, 2010;Bergado et al., 2011). More recently, it has been shown that vagus nerve stimulation triggering release of a mix of neuromodulators gates plasticity (Engineer et al., 2011). Moreover, neuropeptides influence learning and plasticity (Hökfelt et al., 2000;Gøtzsche and Woldbye, 2015). "
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    ABSTRACT: Classical Hebbian learning puts the emphasis on joint pre- and postsynaptic activity, but neglects the potential role of neuromodulators. Since neuromodulators convey information about novelty or reward, the influence of neuromodulatorson synaptic plasticity is useful not just for action learning in classical conditioning, but also to decide 'when' to create new memories in response to a flow of sensory stimuli. In this review, we focus on timing requirements for pre- and postsynaptic activity in conjunction with one or several phasic neuromodulatory signals. While the emphasis of the text is on conceptual models and mathematical theories, we also discuss some experimental evidence for neuromodulation of Spike-Timing-Dependent Plasticity. We highlight the importance of synaptic mechanisms in bridging the temporal gap between sensory stimulation and neuromodulatory signals, and develop a framework for a class of neo-Hebbian three-factor learning rules that depend on presynaptic activity, postsynaptic variables as well as the influence of neuromodulators.
    Preview · Article · Jan 2016 · Frontiers in Neural Circuits
    • "Previous studies [21] [22] used a reduction in cortical EEG power during slow wave sleep to assess effective delivery of VNS in rats. In a first experiment, we examined whether hippocampal EEG during the awake state can also be used to assess effective VNS delivery. "
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    ABSTRACT: Background: Vagus Nerve Stimulation (VNS) has seizure-suppressing effects but the underlying mechanism is not fully understood. To further elucidate the mechanisms underlying VNS-induced seizure suppression at a neurophysiological level, the present study examined effects of VNS on hippocampal excitability using dentate gyrus evoked potentials (EPs) and hippocampal electroencephalography (EEG). Methods: Male Sprague-Dawley rats were implanted with a VNS electrode around the left vagus nerve. A bipolar stimulation electrode was implanted in the left perforant path and a bipolar recording electrode was implanted in the left dentate gyrus for EEG and dentate field EP recording. Following recovery, VNS was applied in freely moving animals, using a duty cycle of 7 s on/18 s off, 30 Hz frequency, 250 µs pulse width, and an intensity of either 0 (SHAM), 25 µA or 1000 µA, while continuously monitoring EEG and dentate field EPs. Results: VNS at 1000 µA modulated dentate field EPs by decreasing the field excitatory post-synaptic potential (fEPSP) slope and increasing the latency and amplitude of the population spike. It additionally influenced hippocampal EEG by slowing theta rhythm from 7 Hz to 5 Hz and reducing theta peak and gamma band power. No effects were observed in the SHAM or 25 µA VNS conditions. Conclusion: VNS modulated hippocampal excitability of freely moving rats in a complex way. It decreased synaptic efficacy, reflected by decreased fEPSP slope and EEG power, but it simultaneously facilitated dentate granule cell discharge indicating depolarization of dentate granule cells.
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