Post-trauma Network Activity
With high-speed calcium imaging and principles of information theory and graph theory, we estimate and characterize the functional connectivity of a neuronal network before- and after-injury with single cell resolution. We then describe the changes in the network topology and attempt to restore activity/architecture to its pre-traumatic state via numerous pharamacologic agents and/or optogenetic tools.
Understanding the role of astrocytes in neuronal signaling may provide the key to attenuating or reversing the sequelae of traumatic injury. Using stochastic molecular dynamics simulations, in vitro studies of glio-neuronal network activity, and in vivo imaging/neurobehavior, we are able to directly interrogate the role of astrocytic gliotransmission on behavioral and cognitive function after injury.
TBI Signaling Cascade
A cortical neuron (GCaMP3,green) and a nearby astrocyte (GFAP,red)
Characterizing the complex signaling cascade following TBI allows us to localize larger cognitive dysfunction to specific receptors and molecular targets. Changes in protein translation, appearance of calcium permeable AMPA receptors, proteolysis of sodium channels, and mitochondrial dysfunction are just a few examples of pathologic alterations that emerge at the single-cell level. The larger scope of our lab is to take these single-cell findings and understand how it scales to the network level, and ultimately, to organism behavior.
Mice in a Spatial Object Recognition task
We use two in vivo models of traumatic brain injury - controlled cortical impact (CCI) and blast.
The severity of CCI can be adjusted to mimic a concussive or a contussive type injury. Blast injury mimics TBI from explosives such as IEDs.
Mice models are used to study to the neurobehavior deficits of TBI and to test the therapeutic potential of various pharmacological agents for attenuating behavior deficits. Each behavior experiment tests the functional integrity of a different brain region. We subject mice to a battery of behavior tests, including: fear conditioning, spatial object recognition, rotorod, zero-maze, and Morris water-maze, to understand the complete spectrum of brain damage.