Decreased cellular excitability of pyramidal tract neurons in primary motor cortex leads to paradoxically increased network activity in simulated parkinsonian motor cortex.

Decreased excitability of pyramidal tract neurons in layer 5B (PT5B) of primary motor cortex (M1) has recently been shown in a dopamine-depleted mouse model of parkinsonism. We hypothesized that decreased PT5B neuron excitability would substantially disrupt oscillatory and non-oscillatory firing patterns of neurons in layer 5 (L5) of primary motor cortex (M1). To test this hypothesis, we performed computer simulations using a previously validated computer model of mouse M1.

Simulating Large-scale Models of Brain Neuronal Circuits using Google Cloud Platform.

Biophysically detailed modeling provides an unmatched method to integrate data from many disparate experimental studies, and manipulate and explore with high precision the resultin brain circuit simulation. We developed a detailed model of the brain motor cortex circuits, simulating over 10,000 biophysically detailed neurons and 30 million synaptic connections. Optimization and evaluation of the cortical model parameters and responses was achieved via parameter exploration using grid search parameter sweeps and evolutionary algorithms.

Advancing translational research with the Semantic Web.

Background: A fundamental goal of the U.S. National Institute of Health (NIH) "Roadmap" is to strengthen Translational Research, defined as the movement of discoveries in basic research to application at the clinical level.