Synaptic Plasticity In Cortex Research Articles

Differences in motor cortex synaptic plasticity associated with two forms of exercise in older adults: Evidence from TMS studies

Differences in motor cortex synaptic plasticity associated with two forms of exercise in older adults: Evidence from TMS studies

Low and high dose methamphetamine differentially regulate synaptic structural plasticity in cortex and hippocampus.

Psychostimulants, such as methamphetamine (METH) can induce structural remodeling of synapses by remodeling presynaptic and postsynaptic morphology. Escalating or long-lasting high dose METH accounts for neurodegeneration by targeting multiple neurotransmitters. However, the effects of low dose METH on synaptic structure and the modulation mechanism remain elusive. This study aims to assess the effects of low dose (2 mg/kg) and high dose (10 mg/kg) of METH on synaptic structure alternation in hippocampus and prefrontal cortex (PFC) and to reveal the underlying mechanism involved in the process. Low dose METH promoted spine formation, synaptic number increase, post-synaptic density length elongation, and memory function. High dose of METH induced synaptic degeneration, neuronal number loss and memory impairment. Moreover, high dose, but not low dose, of METH caused gliosis in PFC and hippocampus. Mechanism-wise, low dose METH inactivated ras-related C3 botulinum toxin substrate 1 (Rac1) and activated cell division control protein 42 homolog (Cdc42); whereas high dose METH inactivated Cdc42 and activated Rac1. We provided evidence that low and high doses of METH differentially regulate synaptic plasticity in cortex and hippocampus.

Second-generation antipsychotic olanzapine attenuates behavioral and prefrontal cortex synaptic plasticity deficits in a neurodevelopmental schizophrenia-related rat model

Second-generation antipsychotics are the drugs of choice for the treatment of neurodevelopmental-related mental diseases such as schizophrenia. Despite the effectiveness of these drugs to ameliorate some of the symptoms of schizophrenia, specifically the positive ones, the mechanisms beyond their antipsychotic effect are still poorly understood. Second-generation antipsychotics are reported to have anti-inflammatory, antioxidant and neuroplastic properties. Using the neonatal ventral hippocampus lesion (nVHL) in the rat, an accepted schizophrenia-related model, we evaluated the effect of the second-generation antipsychotic olanzapine (OLZ) in the behavioral, neuroplastic, and neuroinflammatory alterations exhibited in the nVHL animals. OLZ corrected the hyperlocomotion and impaired working memory of the nVHL rats but failed to enhance social behavior disturbances of these animals. In the prefrontal cortex (PFC), OLZ restored the pyramidal cell structural plasticity in the nVHL rats, enhancing the dendritic arbor length, the spinogenesis and the proportion of mature spines. Moreover, OLZ attenuated astrogliosis as well as some pro-inflammatory, oxidative stress, and apoptosis-related molecules in the PFC. These findings reinforce the evidence of anti-inflammatory, antioxidant, and neurotrophic mechanisms of second-generation antipsychotics in the nVHL schizophrenia-related model, which allows for the possibility of developing more specific drugs for this disorder and thus avoiding the side effects of current schizophrenia treatments.

Motor cortex plasticity response to acute cardiorespiratory exercise and intermittent theta-burst stimulation is attenuated in premanifest and early Huntington\u2019s disease

Huntington’s disease (HD) mouse models suggest that cardiovascular exercise may enhance neuroplasticity and delay disease signs, however, the effects of exercise on neuroplasticity in people with HD are unknown. Using a repeated-measures experimental design, we compared the effects of a single bout of high-intensity exercise, moderate-intensity exercise, or rest, on motor cortex synaptic plasticity in 14 HD CAG-expanded participants (9 premanifest and 5 early manifest) and 20 CAG-healthy control participants, using transcranial magnetic stimulation. Measures of cortico-motor excitability, short-interval intracortical inhibition and intracortical facilitation were obtained before and after a 20-min bout of either high-intensity interval exercise, moderate-intensity continuous exercise, or rest, and again after intermittent theta burst stimulation (iTBS). HD participants showed less inhibition at baseline compared to controls. Whereas the control group showed increased excitability and facilitation following high-intensity exercise and iTBS, the HD group showed no differences in neuroplasticity responses following either exercise intensity or rest, with follow-up Bayesian analyses providing consistent evidence that these effects were absent in the HD group. These findings indicate that exercise-induced synaptic plasticity mechanisms in response to acute exercise may be attenuated in HD, and demonstrate the need for future research to further investigate exercise and plasticity mechanisms in people with HD.

Effect of regulation of the NRG1/ErbB4 signaling pathway on the visual cortex synaptic plasticity of amblyopic adult rats.

This study aimed to investigate the effect of the neuregulin-1/epidermal growth factor 4 (NRG1/ErbB4) signaling pathway on visual cortex synaptic plasticity in adult amblyopic rats with monocular deprivation (MD). Compared with the control group, the P wave latency and amplitude of the MD group were prolonged and low, respectively, with reduced synaptic plasticity-related protein expression, lower number of visual cortex neurons, and increased apoptosis of visual cortex neurons. Recombinant neuregulin-1 (rNRG1) administration activated the NRG1/ErbB4 signaling pathway and improved the visual cortex synaptic plasticity in MD amblyopic rats. However, the effects of rNRG1 were reversed by AG1478 (ErbB4 receptor blockers). The NRG1/ErbB4 signaling pathway in the parvalbumin neurons from MD rats was also inactivated. Amblyopic rats had significantly low cell activity and downregulated expression of synaptic plasticity-related proteins. Thus, exogenous administration of NRG1 can activate ErbB4 signal transduction and improve the damaged synaptic plasticity of the visual cortex among amblyopic rats. Further studies are warranted to explore the potential for clinical management of amblyopia.

The developmental and experience-dependent expression of IGF-2 in mice visual cortex

The circuitry associated with the visual cortex is particularly sensitive to experiences during the early stages of life, which are collectively known as critical periods. Critical period of ocular dominance plasticity is regulated by both environmental and genetic factors. Previous studies demonstrated that IGF-1 significantly influenced the regulation of visual cortex synaptic plasticity. IGF-2 can reportedly regulate synapse formation, dendritic spine maturation, and memory consolidation in rodents. Association between IGF-2 and the regulation of visual cortex synaptic plasticity remains unclear. Here, we first aimed to elucidate the normal expression patterns of IGF-2 and its laminar expression pattern during the process of visual cortex development in mice. This confirmed that IGF-2 may influence the regulation of ocular dominance plasticity in mice. We further elucidated the role of IGF-2 in the regulation of visual cortex synaptic plasticity by examining the effect of monocular deprivation (MD) on IGF-2 expression in the visual cortex. Interestingly, we observed that MD remarkably reduced IGF-2 expression in the visual cortex. Rodents reared in an enriched environment, with enhanced sensory, motor, and social experiences, were capable of effectively accelerating the development of the visual system and could restore normal visual acuity. Although the enriched environment facilitated the restoration of normal visual acuity in the MD mice, IGF-2 expression levels in the visual cortex remained unchanged. Therefore, we considered the possibility that IGF-2 may have a different role with regard to the modulation of plasticity in the visual cortex of the mice, which we aim to study in the future.

Effects of endurance exercise on synaptic plasticity in cerebral cortex of aged rats and related regulatory mechanism

To understand and analyze the rules of endurance exercise on the cerebral cortex adaptive mechanism in aged rats. In this study, 3-month-old (n=20), 13-month-old (n=24) and 23-month-old (n=24) specific-pathogen free (SPF) male Sprague-Dawley Rat (SD) rats were divided into young (Y-SED), middle-aged (M-SED) and old-aged (O-SED) sedentary control group, and the corresponding Y-EX, M-EX and O-EX in the endurance exercise runner group. The 10-weeks of regular moderate-intensity aerobic exercise intervention were carried out in the endurance exercise runner group. The exercise mode is treadmill exercise (slope 0), and the exercise intensity gradually increases from 60%～65% of the maximum oxygen consumption (V·O2max) to 70%～75%, and the exercise time is 10 weeks. Hematoxylin and eosin (HE) staining was used to detect age-related morphological changes. The expressions of superoxide dismutase(SOD) and brain-derived neurotrophic factor (BDNF) and the expressions of synapsin 1 (SYN1) and Ca2+/calmodulin- dependent protein kinases IIα (CaMK IIα) / AMP-activated protein kinase α1(AMPKα1) / mammalian target of rapamycin (mTOR) pathway -related genes were detected. The cerebral cortex structure of the rats in each group showed age-related aging changes, the expression of SOD in the cortex showed a gradual decline, the expression of BDNF showed an age-increasing trend, and the expression levels of SYN1 and CaMK IIα were increased with age. The changes in AMPKα1 and SirT2 and IP3R, AKT1 and mTOR mRNA levels were increased slightly in middle-aged rats and decreased in aged rats. Compared with the rats in each sedentary control group, the nucleus of the cerebral cortex was tightly arranged and the number of nuclei observed under the microscope was increased significantly in each exercise group. Exercise promoted the expressions of SOD, BDNF and synaptophysin SYN1 in the cortex of rats, and the expression levels of SOD and BDNF in aged rats were up-regulated significantly (P＜ 0.01). The expression level of SYN1 in rats was up-regulated significantly (P＜0.05) in the young and aged rats. The expression of CaMK IIα in the cortex of middle-aged and aged rats was up-regulated (P＜0.01), while the expression level of CaMK IIα in young rats was down-regulated (P＜0.01). Exercise could up-regulate the expression level of AMPKα1 in the cortex of young rats (P＜ 0.05), but not in middle-aged and old-age rats. Exercise could up-regulate the expression of SirT2 in the cortex of rats in all age groups (P＜0.05). Exercise up-regulated the expression of phosphoinositide 3-kinase (IP3R)/ protein kinase B 1(AKT1) /mTOR in the cortex of rats, among which young IP3R was significantly up-regulated (P＜0.01) in the young group, mTOR was significantly up-regulated in young and middle-aged group (P＜0.01), and mTOR was also significantly up-regulated in the aged group (P＜0.05). Endurance exercise up-regulates BDNF expression, regulates CaMKIIα signaling, activates AMPK signaling pathway and IP3R / AKT1 / mTOR signaling pathway, and improves synaptic plasticity in the cortex.

Intensity Matters: High-intensity Interval Exercise Enhances Motor Cortex Plasticity More Than Moderate Exercise.

A single bout of cardiovascular exercise can enhance plasticity in human cortex; however, the intensity required for optimal enhancement is debated. We investigated the effect of exercise intensity on motor cortex synaptic plasticity, using transcranial magnetic stimulation. Twenty healthy adults (Mage = 35.10 ± 13.25 years) completed three sessions. Measures of cortico-motor excitability (CME) and inhibition were obtained before and after a 20-min bout of either high-intensity interval exercise, moderate-intensity continuous exercise, or rest, and again after intermittent theta burst stimulation (iTBS). Results showed that high-intensity interval exercise enhanced iTBS plasticity more than rest, evidenced by increased CME and intracortical facilitation, and reduced intracortical inhibition. In comparison, the effect of moderate-intensity exercise was intermediate between high-intensity exercise and rest. Importantly, analysis of each participant's plasticity response profile indicated that high-intensity exercise increased the likelihood of a facilitatory response to iTBS. We also established that the brain-derived neurotrophic factor Val66Met polymorphism attenuated plasticity responses following high-intensity exercise. These findings suggest that high-intensity interval exercise should be considered not only when planning exercise interventions designed to enhance neuroplasticity, but also to maximize the therapeutic potential of non-invasive brain stimulation. Additionally, genetic profiling may enhance efficacy of exercise interventions for brain health.

T016 Repetitive transcranial magnetic stimulation and post-stroke dysphagia

Considerable effort in recent years has been devoted to investigating neurophysiological changes in the brain after stroke and in developing novel strategies to enhance recovery particularlyin the limbs and trunk. In contrast, although dysphagia is a severe complication and can be life threatening in a considerable number of stroke patients, it has not yet received the attention devoted to limb control. In this review, we discuss how introduction of (a) transcranial magnetic stimulation (TMS) to test noninvasively the integrity of the cortico-bulbar swallowing system and (b) the plasticity provoking protocols of rTMS and transcranial direct current stimulation have recently stimulated research into dysphagia after stroke and led to new potential avenues for treatment. We discuss the neural control of swallowing and discuss the contributions of TMS to understand how different brain areas are involved in dysphagia. We also consider recent studies using noninvasive brain stimulation to interact with synaptic plasticity in cortex and enhance recovery of dysphagia following stroke. Although further studies are needed, these investigations provide an important starting point to understand the stimulation parameters and patient characteristics that may influence the optimal response to therapeutic noninvasive brain stimulation. These techniques need to be refined further through a multicenter study so that they can become an essential tool that can be used in academic centers of excellence as well as in a general hospital setting.

A Spiking Working Memory Model Based on Hebbian Short-Term Potentiation

A dominant theory of working memory (WM), referred to as the persistent activity hypothesis, holds that recurrently connected neural networks, presumably located in the prefrontal cortex, encode and maintain WM memory items through sustained elevated activity. Reexamination of experimental data has shown that prefrontal cortex activity in single units during delay periods is much more variable than predicted by such a theory and associated computational models. Alternative models of WM maintenance based on synaptic plasticity, such as short-term nonassociative (non-Hebbian) synaptic facilitation, have been suggested but cannot account for encoding of novel associations. Here we test the hypothesis that a recently identified fast-expressing form of Hebbian synaptic plasticity (associative short-term potentiation) is a possible mechanism for WM encoding and maintenance. Our simulations using a spiking neural network model of cortex reproduce a range of cognitive memory effects in the classical multi-item WM task of encoding and immediate free recall of word lists. Memory reactivation in the model occurs in discrete oscillatory bursts rather than as sustained activity. We relate dynamic network activity as well as key synaptic characteristics to electrophysiological measurements. Our findings support the hypothesis that fast Hebbian short-term potentiation is a key WM mechanism. <b>SIGNIFICANCE STATEMENT</b> Working memory (WM) is a key component of cognition. Hypotheses about the neural mechanism behind WM are currently under revision. Reflecting recent findings of fast Hebbian synaptic plasticity in cortex, we test whether a cortical spiking neural network model with such a mechanism can learn a multi-item WM task (word list learning). We show that our model can reproduce human cognitive phenomena and achieve comparable memory performance in both free and cued recall while being simultaneously compatible with experimental data on structure, connectivity, and neurophysiology of the underlying cortical tissue. These findings are directly relevant to the ongoing paradigm shift in the WM field.

A Spiking Working Memory Model Based on Hebbian Short-Term Potentiation

A dominant theory of working memory (WM), referred to as the persistent activity hypothesis, holds that recurrently connected neural networks, presumably located in the prefrontal cortex, encode and maintain WM memory items through sustained elevated activity. Reexamination of experimental data has shown that prefrontal cortex activity in single units during delay periods is much more variable than predicted by such a theory and associated computational models. Alternative models of WM maintenance based on synaptic plasticity, such as short-term nonassociative (non-Hebbian) synaptic facilitation, have been suggested but cannot account for encoding of novel associations. Here we test the hypothesis that a recently identified fast-expressing form of Hebbian synaptic plasticity (associative short-term potentiation) is a possible mechanism for WM encoding and maintenance. Our simulations using a spiking neural network model of cortex reproduce a range of cognitive memory effects in the classical multi-item WM task of encoding and immediate free recall of word lists. Memory reactivation in the model occurs in discrete oscillatory bursts rather than as sustained activity. We relate dynamic network activity as well as key synaptic characteristics to electrophysiological measurements. Our findings support the hypothesis that fast Hebbian short-term potentiation is a key WM mechanism.SIGNIFICANCE STATEMENT Working memory (WM) is a key component of cognition. Hypotheses about the neural mechanism behind WM are currently under revision. Reflecting recent findings of fast Hebbian synaptic plasticity in cortex, we test whether a cortical spiking neural network model with such a mechanism can learn a multi-item WM task (word list learning). We show that our model can reproduce human cognitive phenomena and achieve comparable memory performance in both free and cued recall while being simultaneously compatible with experimental data on structure, connectivity, and neurophysiology of the underlying cortical tissue. These findings are directly relevant to the ongoing paradigm shift in the WM field.

Infralimbic Neurotrophin-3 Infusion Rescues Fear Extinction Impairment in a Mouse Model of Pathological Fear.

The inability to properly extinguish fear memories constitutes the foundation of several anxiety disorders, including panic disorder. Recent findings show that boosting prefrontal cortex synaptic plasticity potentiates fear extinction, suggesting that therapies that augment synaptic plasticity could prove useful in rescue of fear extinction impairments in this group of disorders. Previously, we reported that mice with selective deregulation of neurotrophic tyrosine kinase receptor, type 3 expression (TgNTRK3) exhibit increased fear memories accompanied by impaired extinction, congruent with an altered activation pattern of the amygdala-hippocampus-medial prefrontal cortex fear circuit. Here we explore the specific role of neurotrophin 3 and its cognate receptor in the medial prefrontal cortex, and its involvement in fear extinction in a pathological context. In this study we combined molecular, behavioral, in vivo pharmacology and ex vivo electrophysiological recordings in TgNTRK3 animals during contextual fear extinction processes. We show that neurotrophin 3 protein levels are increased upon contextual fear extinction in wild-type animals but not in TgNTRK3 mice, which present deficits in infralimbic long-term potentiation. Importantly, infusion of neurotrophin 3 to the medial prefrontal cortex of TgNTRK3 mice rescues contextual fear extinction and ex vivo local application improves medial prefrontal cortex synaptic plasticity. This effect is blocked by inhibition of extracellular signal-regulated kinase phosphorylation through peripheral administration of SL327, suggesting that rescue occurs via this pathway. Our results suggest that stimulating neurotrophin 3-dependent medial prefrontal cortex plasticity could restore contextual fear extinction deficit in pathological fear and could constitute an effective treatment for fear-related disorders.

Dopamine Promotes Motor Cortex Plasticity and Motor Skill Learning via PLC Activation.

Dopaminergic neurons in the ventral tegmental area, the major midbrain nucleus projecting to the motor cortex, play a key role in motor skill learning and motor cortex synaptic plasticity. Dopamine D1 and D2 receptor antagonists exert parallel effects in the motor system: they impair motor skill learning and reduce long-term potentiation. Traditionally, D1 and D2 receptor modulate adenylyl cyclase activity and cyclic adenosine monophosphate accumulation in opposite directions via different G-proteins and bidirectionally modulate protein kinase A (PKA), leading to distinct physiological and behavioral effects. Here we show that D1 and D2 receptor activity influences motor skill acquisition and long term synaptic potentiation via phospholipase C (PLC) activation in rat primary motor cortex. Learning a new forelimb reaching task is severely impaired in the presence of PLC, but not PKA-inhibitor. Similarly, long term potentiation in motor cortex, a mechanism involved in motor skill learning, is reduced when PLC is inhibited but remains unaffected by the PKA inhibitor. Skill learning deficits and reduced synaptic plasticity caused by dopamine antagonists are prevented by co-administration of a PLC agonist. These results provide evidence for a role of intracellular PLC signaling in motor skill learning and associated cortical synaptic plasticity, challenging the traditional view of bidirectional modulation of PKA by D1 and D2 receptors. These findings reveal a novel and important action of dopamine in motor cortex that might be a future target for selective therapeutic interventions to support learning and recovery of movement resulting from injury and disease.

111. Impairment of synaptic plasticity in patients affected by brain tumors

Aim of the present study was to investigate motor cortex synaptic plasticity in both hemispheres of patients affected by brain tumors. We employed an electrophysiological protocol, named repetitive paired associative stimulation (rPAS), involving repetitive transcranial magnetic stimulation (rTMS) paired with electrical stimulation of the contralateral median nerve, that modifies cortico-spinal excitability. Ten right-handed patients (3 women), aged 49–70 years (mean age: 54.8 years), participated in the study. Motor evoked potentials (MEP) were measured at baseline before and for up to 30 min after 5 Hz-rPAS in abductor pollicis brevis (APB). rPAS consisted of 600 pairs of transcranial magnetic stimuli, at a rate of 5 Hz for 2 min, coupled with electrical median nerve stimulation preceding TMS over the contralateral M1 at an interstimulus interval of 25 ms. In both hemispheres of patient with brain tumors rPAS did not induce any significant changes in MEP amplitudes, compared with aged matched healthy controls. Synaptic plasticity is impaired in both hemispheres of patients affected by brain tumors.

144. Evidence of heterosynaptic interactions in human associative plasticity

Paired associative stimulation (PAS) is a method to study motor cortex synaptic plasticity. If a repetitive electrical stimulus to the median nerve is paired with a transcranial magnetic stimulus (TMS) pulse over the controlateral motor cortex at an interstimulus interval (ISI) of 21.5–25 ms, a long term potentiation (LTP)-like synaptic plasticity is induced in the corticospinal system. We investigated the synaptic spatial specificity of PAS25 and PAS21.5, considered to have similar synaptic mechanisms until recently. Eight subjects (28.6 ± 8.3 years) were selected from a sample of 20 subjects because they showed the expected facilitation after both standard PAS protocols and participated to two sessions in which PAS consisted of 360 electrical stimuli (varPAS) paired with TMS over the hotspot of APB. ISI25 ms (varPAS25) and 21.5 ms (varPAS21.5) were randomly delivered for a total of 360 stimuli. Since cerebellar transcranial direct stimulation (TDCS) can abolish the effects of PAS25, either sham or anodal TDCS (2 mA,30 min) was applied to the cerebellum simultaneously with PAS (anodal-varPAS and sham-varPAS). We measured MEPs before and after each intervention. Randomly delivered PAS25 and PAS21.5 (sham-varPAS) blocked the induction of PAS plasticity while the concurrent anodal TDCS (anodal-varPAS) restored the expected effect. PAS25 and PAS21.5 are inducing LTP-like synaptic plasticity with different synaptic spatial specificity. Heterosynaptic LTD-like modulation might well explain the loss of effect of combining PAS21.5 and PAS25.

Nitric oxide‐dependent long‐term depression but not endocannabinoid‐mediated long‐term potentiation is crucial for visual recognition memory

Synaptic plasticity in perirhinal cortex is essential for recognition memory. Nitric oxide and endocannabinoids (eCBs), which are produced in the postsynaptic cell and act on the presynaptic terminal, are implicated in mechanisms of long-term potentiation (LTP) and long-term depression (LTD) in other brain regions. In this study, we examine these two retrograde signalling cascades in perirhinal cortex synaptic plasticity and in visual recognition memory in the rat. We show that inhibition of NO-dependent signalling prevented both carbachol- and activity (5 Hz)-dependent LTD but not activity (100 Hz theta burst)-dependent LTP in the rat perirhinal cortex in vitro. In contrast, inhibition of the eCB-dependent signalling prevented LTP but not the two forms of LTD in vitro. Local administration into perirhinal cortex of the nitric oxide synthase inhibitor NPA (2 μm) disrupted acquisition of long-term visual recognition memory. In contrast, AM251 (10 μm), a cannabinoid receptor 1 antagonist, did not impair visual recognition memory. The results of this study demonstrate dissociation between putative retrograde signalling mechanisms in LTD and LTP in perirhinal cortex. Thus, LTP relies on cannabinoid but not NO signalling, whilst LTD relies on NO- but not eCB-dependent signalling. Critically, these results also establish, for the first time, that NO- but not eCB-dependent signalling is important in perirhinal cortex-dependent visual recognition memory.

Noninvasive Brain Stimulation for Treatment of Post-Stroke Dysphagia

Considerable effort in recent years has been devoted to investigating neurophysiological changes in the brain after stroke and in developing novel strategies to enhance recovery particularly in the limbs and trunk. In contrast, although dysphagia is a severe complication and can be life threatening in a considerable number of stroke patients, it has not yet received the attention devoted to limb control. In this review, we discuss how introduction of (a) transcranial magnetic stimulation (TMS) to test noninvasively the integrity of the cortico-bulbar swallowing system and (b) the plasticity provoking protocols of rTMS and transcranial direct current stimulation have recently stimulated research into dysphagia after stroke and led to new potential avenues for treatment. We discuss the neural control of swallowing and discuss the contributions of TMS to understand how different brain areas are involved in dysphagia. We also consider recent studies using noninvasive brain stimulation to interact with synaptic plasticity in cortex and enhance recovery of dysphagia following stroke. Although further studies are needed, these investigations provide an important starting point to understand the stimulation parameters and patient characteristics that may influence the optimal response to therapeutic noninvasive brain stimulation. These techniques need to be refined further through a multicenter study so that they can become an essential tool that can be used in academic centers of excellence as well as in a general hospital setting.

Cerebellar modulation of human associative plasticity

Paired associative stimulation (PAS) is a method commonly used in human studies of motor cortex synaptic plasticity. It involves repeated pairs of electrical stimuli to the median nerve and transcranial magnetic stimulation (TMS) of the motor cortex. If the interval between peripheral and TMS stimulation is around 21–25 ms, corticospinal excitability is increased for the following 30–60 min via a long term potentiation (LTP)-like effect within the primary motor cortex. Previous work has shown that PAS depends on the present and previous levels of activity in cortex, and that it can be modified by motor learning or attention. Here we show that simultaneous transcranial direct current stimulation (TDCS; 2 mA) over the cerebellum can abolish the PAS effect entirely. Surprisingly, the effect is seen when the PAS interval is 25 ms but not when it is 21.5 ms. There are two implications from this work. First, the cerebellum influences PAS effects in motor cortex; second, LTP-like effects of PAS have at least two different mechanisms. The results are relevant for interpretation of pathological changes that have been reported in response to PAS in people with movement disorders and to changes in healthy individuals following exercise or other interventions.

P4‐469: Chronic treatment with rivastigmine does not modify primary motor cortex synaptic plasticity in patients with Alzheimer's disease (AD): a repetitive transcranial magnetic stimulation (rTMS) study

P4‐469: Chronic treatment with rivastigmine does not modify primary motor cortex synaptic plasticity in patients with Alzheimer's disease (AD): a repetitive transcranial magnetic stimulation (rTMS) study

P20.6 Rivastigmine doesn't modify motor cortex synaptic plasticity in patients with Alzheimer's disease (AD): a repetitive transcranial magnetic stimulation (rTMS) study

P20.6 Rivastigmine doesn't modify motor cortex synaptic plasticity in patients with Alzheimer's disease (AD): a repetitive transcranial magnetic stimulation (rTMS) study