title: Impaired synaptic plasticity in RASopathies: a mini-review.
abstract: Synaptic plasticity in the form of long-term potentiation (LTP) and long-term depression (LTD) is considered to be the neurophysiological correlate of learning and memory. Impairments are discussed to be one of the underlying pathophysiological mechanisms of developmental disorders. In so-called RASopathies [e.g., neurofibromatosis 1 (NF1)], neurocognitive impairments are frequent and are affected by components of the RAS pathway which lead to impairments in synaptic plasticity. Transcranial magnetic stimulation (TMS) provides a non-invasive method to investigate synaptic plasticity in humans. Here, we review studies using TMS to evaluate synaptic plasticity in patients with RASopathies. Patients with NF1 and Noonan syndrome (NS) showed reduced cortical LTP-like synaptic plasticity. In contrast, increased LTP-like synaptic plasticity has been shown in Costello syndrome. Notably, lovastatin normalized impaired LTP-like plasticity and increased intracortical inhibition in patients with NF1. TMS has been shown to be a safe and efficient method to investigate synaptic plasticity and intracortical inhibition in patients with RASopathies. Deeper insights in impairments of synaptic plasticity in RASopathies could help to develop new options for the therapy of learning deficits in these patients.
authors: Department of Pediatrics, Kinderzentrum München gemeinnützige GmbH, Technische Universität München, Heiglhofstrasse 63, 81377, Munich, Germany.|Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg im Breisgau, Germany.
authors: Florian
authors: F
authors: Mainberger
authors: Department of Pediatrics, Kinderzentrum München gemeinnützige GmbH, Technische Universität München, Heiglhofstrasse 63, 81377, Munich, Germany.|Department of Anaesthesiology and Critical Care Medicine, Freiburg University Medical Center, Freiburg, Germany.
authors: Susanne
authors: S
authors: Langer
authors: Department of Pediatrics, Kinderzentrum München gemeinnützige GmbH, Technische Universität München, Heiglhofstrasse 63, 81377, Munich, Germany.
authors: Volker
authors: V
authors: Mall
authors: Department of Pediatrics, Kinderzentrum München gemeinnützige GmbH, Technische Universität München, Heiglhofstrasse 63, 81377, Munich, Germany. nikolai.jung@tum.de.
authors: Nikolai H
authors: NH
authors: Jung
mesh_terms: D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D006801:Humans; D009044:Motor Cortex / Q000503:physiopathology*; D009433:Neural Inhibition / Q000502:physiology*; D009456:Neurofibromatosis 1 / Q000473:pathology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009634:Noonan Syndrome / Q000473:pathology*; D050781:Transcranial Magnetic Stimulation
keywords: Costello syndrome; Long-term potentiation; Neurofibromatosis type 1; Noonan syndrome; RASopathies; Synaptic plasticity; Transcranial magnetic stimulation