RESUMEN
We have developed an open-source software for neuroscientists to analyze electrophysiological recordings. Named SimplyFire, the software gives the users the flexibility to analyze a variety of recordings using an interactive graphical user interface or as an importable Python package. The software features a simple plugin structure that allows users to create and deploy various electrophysiology analysis tools. SimplyFire is pre-packaged with tools commonly used in electrophysiology, such as noise filtering, trace averaging, miniature analysis, and trace exporting. We discuss in detail the algorithm behind the different features of the analysis tool. We verify the accuracy of the algorithm by testing the software using computer-generated traces with known true values of the events. SimplyFire will be distributed under the GPLv3.0 license. The open nature of this software will allow interested investigators to modify and expand the software for additional capabilities as needed. We believe this software will not only compete with commercially available software packages but will also present a powerful tool to meet the current and unmet needs of electrophysiologists.
Asunto(s)
Algoritmos , Programas InformáticosRESUMEN
Synaptic plasticity is obstructed by pathogenic tau in the brain, representing a key mechanism that underlies memory loss in Alzheimer's disease (AD) and related tauopathies. Here, we found that reduced levels of the memory-associated protein KIdney/BRAin (KIBRA) in the brain and increased KIBRA protein levels in cerebrospinal fluid are associated with cognitive impairment and pathological tau levels in disease. We next defined a mechanism for plasticity repair in vulnerable neurons using the C-terminus of the KIBRA protein (CT-KIBRA). We showed that CT-KIBRA restored plasticity and memory in transgenic mice expressing pathogenic human tau; however, CT-KIBRA did not alter tau levels or prevent tau-induced synapse loss. Instead, we found that CT-KIBRA stabilized the protein kinase Mζ (PKMζ) to maintain synaptic plasticity and memory despite tau-mediated pathogenesis. Thus, our results distinguished KIBRA both as a biomarker of synapse dysfunction and as the foundation for a synapse repair mechanism to reverse cognitive impairment in tauopathy.
Asunto(s)
Enfermedad de Alzheimer , Resiliencia Psicológica , Tauopatías , Ratones , Animales , Humanos , Proteínas tau/genética , Proteínas tau/metabolismo , Tauopatías/genética , Tauopatías/metabolismo , Tauopatías/patología , Encéfalo/metabolismo , Enfermedad de Alzheimer/patología , Trastornos de la Memoria/genética , Trastornos de la Memoria/metabolismo , Plasticidad Neuronal , Ratones Transgénicos , Riñón/metabolismo , Modelos Animales de EnfermedadRESUMEN
Synaptic plasticity is obstructed by pathogenic tau in the brain, representing a key mechanism that underlies memory loss in Alzheimer's disease (AD) and related tauopathies. Here, we define a mechanism for plasticity repair in vulnerable neurons using the C-terminus of the KIdney/BRAin (KIBRA) protein (CT-KIBRA). We show that CT-KIBRA restores plasticity and memory in transgenic mice expressing pathogenic human tau; however, CT-KIBRA did not alter tau levels or prevent tau-induced synapse loss. Instead, we find that CT-KIBRA binds to and stabilizes protein kinase Mζ (PKMζ) to maintain synaptic plasticity and memory despite tau-mediated pathogenesis. In humans we find that reduced KIBRA in brain and increased KIBRA in cerebrospinal fluid are associated with cognitive impairment and pathological tau levels in disease. Thus, our results distinguish KIBRA both as a novel biomarker of synapse dysfunction in AD and as the foundation for a synapse repair mechanism to reverse cognitive impairment in tauopathy.