Prince Lab Research


Work in the Prince lab has focused on normal and abnormal regulation of excitability in neurons of mammalian cerebral cortex and thalamus and mechanisms underlying development and prophylaxis of epilepsy in animal models. Long-term goals are to understand how cortical injury and other pathological processes induce changes in structure and function of neurons and neuronal networks that lead to hyperexcitability and epileptogenesis.

With this information, it will be possible to devise experimental strategies to prevent the occurrence of epilepsy after cortical injury and eventually apply them to individuals with significant brain trauma. We have already provided a proof in principal that prophylaxis of posttraumatic epilepsy is possible, using a rat model.

Current Projects:

  • Modulation of interneuronal function in neocortex. Role of transmitters and modulators in selectively altering activities in subgroups of neocortical interneurons. Functional role of autaptic transmission in fast-spiking interneurons. Na+-K+ atpase as a modulator of interneuronal and pyramidal cell activities. Modulation of GABA release from low threshold spiking interneurons by cannabinoids. Effects of TrkB activation by small molecules on interneuronal structure and function after neocortical injury.Supported by NS39579

  • Reorganization of neocortical neuronal synaptic and intrinsic neuronal properties after cortical trauma. Functional and structural alterations in pyramidal cells and interneurons in models of chronic epileptogenesis, including microgyral developmental malformations, partial neocortical isolations, and post-pilocarpine epilepsy. Whole cell recordings and laser scanning photostimulation of caged glutamate to assess excitatory and inhibitory connectivity, biocytin filled reconstructed interneurons. Electrophysiological and neuroanatomical studies of axonal sprouting following chronic neocortical injury and alterations in expression and function of Na+-K+ ATPase. Supported by NS12151

  • Effects of clinically relevant chronic neocortical injuries on thalamic function in nucleus reticularis and relay nuclei. Whole cell recordings, immunocytochemistry, in vivo video/EEG monitoring; Rose Bengal stroke model; focal neocortical status epilepticus. Supported by NS06477

  • Actions of transmitters and neuropeptides within intra-thalamic circuits as they relate to rhythmic activities and models of petit mal epilepsy. Supported by NS06477

  • Prophylaxis of posttraumatic epilepsy in partially isolated neocortex. Gabapentin as an antiepileptogenic drug in the undercut model of epilepsy. “Rescue” of injured fast-spiking interneurons by activation of TrkB receptors with a small molecule partial agonist. Supported by The Cure Foundation and NS12151.

  • Structural and functional changes in epileptogenic developmental cortical malformations. Supported by NS12151

Research Techniques/Tools:

Whole cell recordings of visualized pyramidal cells and interneurons in rats and mice in in vitro brain slices, including paired recordings to assess unitary synaptic events.

Use of genetically altered mice. GFP-labeled cells and knockouts to study alterations in selective neuronal subtypes and impact of gene mutations on neocortical structure/function.

Chronic epileptogenic lesional models in rat and mouse, including production of developmental malformations.

Methods for analysis of actions of transmitters and modulators including neuropeptides on neuronal and circuit function. Intracellular perfusions, focal extracellular drug applications.

Laser scanning photostimulation of caged compounds in brain slices for analysis of cell properties and connectivity.

Anatomical techniques: Quantitative analysis of structure of single electrophysiologically characterized neurons using Neurolucida and confocal microscopy in conjunction with immunocytochemistry to identify and localize protein species. In situ hybridization. Ortho- and retrograde labeling.

Chronic in vivo video-EEG monitoring of implanted rats and mice