A Computational Model of Mitochondria Motility in Axons.

Mitochondria play a critical role in regulating cellular processes including ATP production, intracellular calcium signaling and generation of reactive oxidative species (ROS). Neurons rely on mitochondrial function to perform a range of complex processes, and mitochondrial dysfunctions have been shown to have an impact in pathologies of the nervous system. Yet, neurons contain a finite number of mitochondria, and their location is known to change in response to a number of factors including age and cellular activity, thereby impacting neuronal response.

A Computational Model of the Cholinergic Modulation of CA1 Pyramidal Cell Activity.

Dysfunction in cholinergic modulation has been linked to a variety of cognitive disorders including Alzheimer's disease. The important role of this neurotransmitter has been explored in a variety of experiments, yet many questions remain unanswered about the contribution of cholinergic modulation to healthy hippocampal function. To address this question, we have developed a model of CA1 pyramidal neuron that takes into consideration muscarinic receptor activation in response to changes in extracellular concentration of acetylcholine and its effects on cellular excitability and downstream intracellular calcium dynamics.

ROOTS: An Algorithm to Generate Biologically Realistic Cortical Axons and an Application to Electroceutical Modeling.

Advances in computation and neuronal modeling have enabled the study of entire neural tissue systems with an impressive degree of biological realism. These efforts have focused largely on modeling dendrites and somas while largely neglecting axons. The need for biologically realistic explicit axonal models is particularly clear for applications involving clinical and therapeutic electrical stimulation because axons are generally more excitable than other neuroanatomical subunits.

Pathogenic Processes Underlying Alzheimer's Disease: Modeling the Effects of Amyloid Beta on Synaptic Transmission.

The molecular mechanisms underlying Alzheimer's disease (AD) have been and are still under heavy scrutiny to better understand what leads to the onset and progression of the disease, and to design and develop efficacious therapeutic strategies. These decade-long studies have taught us a lot regarding the various molecular pathways involved in the pathology, but a complete dynamic picture of the underlying pathological mechanisms is still missing.We propose to provide a technological answer to fill this gap by developing and using a computational approach that integrates AD-related experimental findings and their effects on multiple aspects of neuronal function.

Cholinergic Modulation of CA1 Pyramidal Cells via M1 Muscarinic Receptor Activation: A Computational Study at Physiological and Supraphysiological Levels.

The hippocampus receives extensive cholinergic modulation from the basal forebrain, which has been shown to have a prominent role in attention, learning, and synaptic plasticity. Disruptions of this modulation have been linked to a variety of neural disorders including Alzheimer's Disease. Pyramidal cells of the CA1 region of the hippocampus express several cholinergic receptor types in different locations throughout the cells' morphology.

A Glutamatergic Spine Model to Enable Multi-Scale Modeling of Nonlinear Calcium Dynamics.

In synapses, calcium is required for modulating synaptic transmission, plasticity, synaptogenesis, and synaptic pruning. The regulation of calcium dynamics within neurons involves cellular mechanisms such as synaptically activated channels and pumps, calcium buffers, and calcium sequestrating organelles. Many experimental studies tend to focus on only one or a small number of these mechanisms, as technical limitations make it difficult to observe all features at once.