Published: The team proposes intra-cell-type heterogeneity as a new mechanism for sculpting the computational properties of local circuits of excitatory and inhibitory spiking neurons, permitting the same canonical microcircuit to be tuned for diverse computational tasks. This work may serve as the basis for examining the effects of neural heterogeneity in more specific brain systems, such as the basal ganglia. View original preprint.
Manual isolation of nuclei from human brain using CellRaft device and single nucleus Whole Genome Amplificationon
Protocol for manual nuclear isolation from human brain tissue using Cell Raft device for single cell Whole Genome Amplification Protocol for manual nuclear isolation from human brain tissue using Cell Raft device for single cell Whole Genome Amplification
Published: The main purpose of the paper is to demonstrate how these three tools can support the computational/mathematical modeling of neural systems with a variety of numerical methods that are well tested and documented. Thus, the authors present a powerful tool kit for computational/mathematical approaches to studying the dynamics and functions of complex neural systems such as the basal ganglia. View original preprint.
Single-cell Whole Genome Amplification (scWGA) of human post-mortem brain samples isolated by Laser Capture Microdissection (LCM)on
This protocol uses Laser Capture Microdissection (LCM) technology on human post-mortem brain tissue slides with rapid Giemsa staining to isolate single nuclei for Single-cell Whole Genome Amplification (scWGA) in order to do low coverage (<1x) single-cell whole genome sequencing to detect mega-base somatic Copy Number Variations (CNVs).
ICC confocal images: Protein aggregation and calcium dysregulation are the earliest hallmarks of familial Parkinson’s disease in human midbrain dopaminergic neuronson
Our differentiation paradigm generates an efficient model for studying disease mechanisms in PD, and highlights that protein misfolding to generate intraneuronal oligomers is one of the earliest critical events driving disease in human neurons, rather than a late-stage hallmark of the disease.
Preprint: This sensitive, computationally efficient approach enables fluorescent puncta and cellular features to be distinguished in cellular and tissue environments with a sensitivity down to the level of the single protein.
TX2P allows for automated integration of mass spectometry data in long-read RNA-sequencing workflow. It does so by predicting open reading frames for each transcripts within an input GTF/GFF file, translates it into peptide sequences and then searches for those predicted proteins in mass spec datasets using MetaMorpheus.
Feeding protocol for Ndufs2fl/fl mice,
To understand PD-associated sleep-wake abnormalities, a new progressive model of PD - the MCI-Park mouse - was studied. Near the transition to the parkinsonian state, these mice exhibited significantly altered sleep-wake regulation, including increased wakefulness, decreased non-rapid eye movement (NREM) sleep, increased sleep fragmentation, reduced rapid eye movement (REM) sleep, and altered EEG activity patterns.
State-dependent GABAergic regulation of striatal spiny projection neuron excitability: NEURON + Python model of striatal projection neuronson
This repository contains a NEURON + Python model of striatal projection neurons (or SPNs) designed to simulate the interaction between GABAergic and glutamatergic synaptic inputs.
This protocols describes the RiboTag virus vectors injected into mouse brain, tissue dissection, immunoprecipitation and RNA extraction for RNAseq.
Surgery and setups for recording 24-hour natural sleep/wake cycles in mice.
While the basal ganglia circuit model underpinning the notion that striatal dopamine (DA) depletion was the critical determinant of network pathophysiology underlying the motor symptoms of Parkinson’s disease, the hypothesis itself has never been directly tested. It is time for a new model of the network determinants of motor disability in PD.
Recurrent neural network training in Python (RectiPy) is a software package developed by Richard Gast that allows for lightweight implementations of recurrent neural networks (RNNs) based on ordinary or delayed differential equations. Here, the team provides a tool that allows for the implementation of biologically informed spiking neural networks and optimizes the parameters of these networks via gradient descent.
α-Synuclein pathology disrupts mitochondrial function in dopaminergic and cholinergic neurons at-risk in Parkinson’s diseaseon
The mechanisms by which intracellular aSYN pathology contributes to dysfunction and degeneration of neurons in the brain are still unclear. Genetic and physiological methods were used to monitor mitochondrial function in substantia nigra pars compacta (SNc) dopaminergic and pedunculopontine nucleus (PPN) cholinergic neurons after stereotaxic injection of aSYN pre-formed fibrils (PFFs) into the mouse brain.
Motor learning selectively strengthens cortical and striatal synapses of motor engram neurons Dataseton
This upload includes 1) ImageJ macros / scripts for minor automated cell counting for brain slides with immunostaining and 2) MATLAB functions / scripts for minor automated spine location cluster analysis (nearest neighbor distance / index).
This repository contains five Jupyter Notebooks (Python 3.0) created or modified for specific use with action potential analysis for the Zampese, et.al. 2022 Science Advances paper.
Source data for “Ca2+ channels couple spiking to mitochondrial metabolism in substantia nigra dopaminergic neurons”on
Source data for publication: "Ca2+ channels couple spiking to mitochondrial metabolism in substantia nigra dopaminergic neurons."
Published: Reinforcement mechanism promotes not only reinforcement, but gradual refinement of the entire behavioral repertoire to assign credit to specific actions and action sequences that lead to dopamine release.
Datasets for all figures 1-8 in: GABAergic regulation of striatal spiny projection neuron excitability depends upon their activity state Image is taken from Fig 1B inset and illustrates RiboTag-eGFP in SPNs of the striatum.