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Catalog
ASAP is committed to accelerating the pace of discovery and informing a path to a cure for Parkinson’s disease through collaboration, research-enabling resources, and data sharing. We’ve created this catalog to showcase the research outputs and tools developed by ASAP-funded programs.
Article
Rethinking the network determinants of motor disability in Parkinson’s disease
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.
Teams
Article
Neural heterogeneity controls computations in spiking neural networks
Published: The authors want to understand how neural heterogeneity affect macroscopic neural dynamics and contribute to neurodynamic functions. Here, the authors study the macroscopic dynamics of networks of heterogeneous Izhikevich neurons. Their analysis suggests that the level of heterogeneity of inhibitory populations controls resonance and hysteresis properties of systems of coupled excitatory and inhibitory neurons. View original preprint.
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Article
Macroscopic dynamics of neural networks with heterogeneous spiking thresholds
Published: The authors develop a new computational model to represent different neuron types and spiking dynamics. The model is comprised of biophysical state variables and parameters, incorporates realistic spike resetting conditions, and accounts for heterogeneity in neural spiking thresholds. These features allow for a broad applicability of the model as well as for a direct comparison to experimental data. View original preprint.
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Article
Feed-forward metabotropic signaling by Cav1 Ca2+ channels supports pacemaking in pedunculopontine cholinergic neurons
Published: Like a handful of other neuronal types in the brain, cholinergic neurons (CNs) in the pedunculopontine nucleus (PPN) are lost in the course of Parkinson’s disease (PD). PPN CNs have a distinctive physiological phenotype that shares some, but not all, of the features of other neurons that are selectively vulnerable in PD. View original preprint.
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Article
Dynamic behaviour restructuring mediates dopamine-dependent credit assignment
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.
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Article
α-Synuclein pathology disrupts mitochondrial function in dopaminergic and cholinergic neurons at-risk in Parkinson’s disease
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.
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Article
Ca2+ channels couple spiking to mitochondrial metabolism in substantia nigra dopaminergic neurons
Published: The authors explore how cellular energy production and demand are matched. By studying the pacemaking activity of dopaminergic neurons using a combination of electrophysiolocal, optical, and molecular method, they found that spike- activated calcium ion entry triggered calcium ion release from the ER, causing mitochondrial oxidative phosphorylation to occur through two calcium-dependent mechanisms.
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Article
Disrupted sleep-wake regulation in the MCI-Park mouse model of Parkinson’s disease
Published: 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. View original preprint.
Teams
Article
PyRates—A code-generation tool for modeling dynamical systems in biology and beyond
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.
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Article
State-dependent GABAergic regulation of striatal spiny projection neuron excitability
Our results demonstrate that GABAARs can work in concert with iGluRs to excite adult SPNs when they are in the resting down-state, suggesting that their inhibitory role is limited to brief periods near spike threshold. This state-dependence calls for a reformulation of the role intrastriatal GABAergic circuits.
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Article
Dopamine neuron activity encodes the length of upcoming contralateral movement sequences
The relationship between the activity of dopaminergic neurons (DANs) and the length of movement sequences is unknown. The authors imaged the activity of SNc DANs in mice. Results indicate that movement-initiation DANs encode more than a general motivation signal and invigorate aspects of contralateral movements. View original preprint.
Article
Motor learning selectively strengthens cortical and striatal synapses of motor engram neurons
Publication: Learning and consolidating new motor skills require plasticity in the motor cortex and striatum, two key motor regions of the brain. However, how neurons undergo synaptic changes and become recruited during motor learning to form a memory remains unknown. Here the authors identify M1 engram neurons important for memory.
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