3-Dimensional morphological characterization of neuroretinal microglia in Alzheimer's disease via machine learning.

Alzheimer's Disease (AD) is a debilitating neurodegenerative disease that affects 47.5 million people worldwide. AD is characterised by the formation of plaques containing extracellular amyloid-β (Aβ) and neurofibrillary tangles composed of hyper-phosphorylated tau proteins (pTau).

Mechanisms of synapse-to-nucleus calcium signalling in striatal neurons and impairments in Huntington's disease.

Huntington's disease (HD) is a monogenic disorder with autosomal dominant inheritance. In HD patients, neurons in the striatum and cortex degenerate, leading to motor, psychiatric and cognitive disorders. Dysregulated synaptic function and calcium handling are common in many neurodegenerative diseases, including HD.

CellPalmSeq: A curated RNAseq database of palmitoylating and de-palmitoylating enzyme expression in human cell types and laboratory cell lines.

The reversible lipid modification protein S-palmitoylation can dynamically modify the localization, diffusion, function, conformation and physical interactions of substrate proteins. Dysregulated S-palmitoylation is associated with a multitude of human diseases including brain and metabolic disorders, viral infection and cancer. However, the diverse expression patterns of the genes that regulate palmitoylation in the broad range of human cell types are currently unexplored, and their expression in commonly used cell lines that are the workhorse of basic and preclinical research are often overlooked when studying palmitoylation dependent processes.

Exploring the expression patterns of palmitoylating and de-palmitoylating enzymes in the mouse brain using the curated RNA-seq database BrainPalmSeq.

Protein -palmitoylation is a reversible post-translational lipid modification that plays a critical role in neuronal development and plasticity, while dysregulated -palmitoylation underlies a number of severe neurological disorders. Dynamic -palmitoylation is regulated by a large family of ZDHHC palmitoylating enzymes, their accessory proteins, and a small number of known de-palmitoylating enzymes. Here, we curated and analyzed expression data for the proteins that regulate -palmitoylation from publicly available RNAseq datasets, providing a comprehensive overview of their distribution in the mouse nervous system.

Quantifying neuronal structural changes over time using dynamic morphometrics.

Brain circuit development involves tremendous structural formation and rearrangement of dendrites, axons, and the synaptic connections between them. Direct studies of neuronal morphogenesis are now possible through recent developments in multiple technologies, including single-neuron labeling, time-lapse imaging in intact tissues, and 4D rendering software capable of tracking neural growth over periods spanning minutes to days. These methods allow detailed quantification of structural changes of neurons over time, called dynamic morphometrics, providing new insights into fundamental growth patterns, underlying molecular mechanisms, and the intertwined influences of external factors, including neural activity, and intrinsic genetic programs.

Bulk Dye Loading for In Vivo Calcium Imaging of Visual Responses in Populations of Tectal Neurons.

Bulk loading of neurons with fluorescent calcium indicators in transparent albino tadpoles offers a rapid and easy method for tracking sensory-evoked activity in large numbers of neurons within an awake developing brain circuit. In vivo two-photon time-lapse imaging of an image plane through the optic tectum allows defining receptive field properties from visual-evoked responses for studies of single-neuron and network-level encoding and plasticity. Here, we describe loading the tadpole optic tectum with the membrane-permeable AM ester of Oregon Green 488 BAPTA-1 (OGB-1 AM) for in vivo imaging experiments.