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Activity Dependent Regulation Of Neurotransmitter Receptors And Ion Channels During Developement

Investigators:
John W. Swann, Ph.D.
Adam Meyer
Trang Lam

The focus of our laboratory is on understanding how long term alterations in neuronal activity regulates the expression of glutamate receptors and L-type Ca+2 channels during hippocampal development.  Studies of both pyramidal cells and identified subpopulations of interneurons are conducted.  Well developed in vivo and in vitro models are used.  A multidisciplinary approach is taken including: patch clamp electrophysiology, microanatomical studies of intracellularly dye injected, gene transfected and immunohistochemically processed neurons. 

Quantitative immunoblotting and real time confocal imaging of receptor and ion channel trafficking are also underway.  The cellular and molecular mechanisms underlying homeostatic plasticity are explored since chronic activity blockade leads to increases and prolonged hyperactivity to decreases in both the expression and targeting of glutamate receptor and calcium channel subunits. Results of these studies have important implication on how epilepsy arises in the developing brain and the impact seizures have on normal brain development.

Galvan, C., Hrachovy, R., Smith, K. and Swann, J.  Blockade of neuronal activity during hippocampal development produces a chronic focal epilepsy in the rat.  J. Neuroscience, 20:2904-2916, 2000.

Oliva, A.A. Jr., Jiang, M., Lam, T., Smith, K. and Swann, J.W.  Novel Hippocampal Interneuronal Subtypes Identified Using Transgenic Mice that Express Green Fluorescent Protein (GFP) in GABAergic Interneurons.  J. Neuroscience, 20:3354-3368, 2000.

Al-Noori, S. and Swann, J.  A role for sodium and chloride in kainic acid - induced beading of inhibitory interneuron dendrites.  Neuroscience, 101:337-348, 2000.

Swann J.W., Al-Noori, S.,  Jiang,  M., Lee, C.L.  Spine loss and other dendritic abnormalities in epilepsy.  Hippocampus, 10:617-625, 2000.

Swann, J.W., Smith, K.L., Lee, C.L.  Neuronal activity and the establishment of normal and epileptic circuits during brain development.  In: International Review of Neurobiology Brain Plasticity and Epilepsy, 45:89-118, 2001.

Jiang, M., Oliva, A.A. Jr., Lam, T. and and Swann, J.W.  GABAergic Neurons That Pioneer Hippocampal Area CA1 of the Mouse: Morphological Features and Multiple Fates.  Journal of Comparative Neurology, 439:176-192, 2001.

Lee,C.L., Hannay, J., Hrachovy, R., Rashid, S., Antalffy, B. and Swann, J.W.  Recurrent seizures in infant rats produce spatial learning deficits without a substantial loss of hippocampal pyramidal cells.  Neuroscience, 107:71-84, 2001.

 

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Gordon and Mary Cain Pediatric Neurology Research Foundation Laboratories
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Last Modified: April 26, 2006