A NWB-based dataset and processing pipeline of human single-neuron activity during a declarative memory task.

A challenge for data sharing in systems neuroscience is the multitude of different data formats used. Neurodata Without Borders: Neurophysiology 2.0 (NWB:N) has emerged as a standardized data format for the storage of cellular-level data together with meta-data, stimulus information, and behavior. A key next step to facilitate NWB:N adoption is to provide easy to use processing pipelines to import/export data from/to NWB:N. Here, we present a NWB-formatted dataset of 1863 single neurons recorded from the medial temporal lobes of 59 human subjects undergoing intracranial monitoring while they performed a recognition memory task. We provide code to analyze and export/import stimuli, behavior, and electrophysiological recordings to/from NWB in both MATLAB and Python. The data files are NWB:N compliant, which affords interoperability between programming languages and operating systems. This combined data and code release is a case study for how to utilize NWB:N for human single-neuron recordings and enables easy re-use of this hard-to-obtain data for both teaching and research on the mechanisms of human memory.

Molecular chaperones as rational drug targets for Parkinson's disease therapeutics.

Parkinson's disease is a neurodegenerative movement disorder that is caused, in part, by the loss of dopaminergic neurons within the substantia nigra pars compacta of the basal ganglia. The presence of intracellular protein aggregates, known as Lewy bodies and Lewy neurites, within the surviving nigral neurons is the defining neuropathological feature of the disease. Accordingly, the identification of specific genes mutated in families with Parkinson's disease and of genetic susceptibility variants for idiopathic Parkinson's disease has implicated abnormalities in proteostasis, or the handling and elimination of misfolded proteins, in the pathogenesis of this neurodegenerative disorder. Protein folding and the refolding of misfolded proteins are regulated by a network of interactive molecules, known as the chaperone system, which is composed of molecular chaperones and co-chaperones. The chaperone system is intimately associated with the ubiquitin-proteasome system and the autophagy-lysosomal pathway which are responsible for elimination of misfolded proteins and protein quality control. In addition to their role in proteostasis, some chaperone molecules are involved in the regulation of cell death pathways. Here we review the role of the molecular chaperones Hsp70 and Hsp90, and the cochaperones Hsp40, BAG family members such as BAG5, CHIP and Hip in modulating neuronal death with a focus on dopaminergic neurodegeneration in Parkinson's disease. We also review current progress in preclinical studies aimed at targetting the chaperone system to prevent neurodegeneration. Finally, we discuss potential future chaperone-based therapeutics for the symptomatic treatment and possible disease modification of Parkinson's disease.