Lecture Notes

Oligodendrocytes are responsible for myelinating axon fibers in the central nervous system. At the Nodes of Ranvier, clustering of sodium and potassium channels is highly regulated and occurs after myelination of the axon fibers. This week, we will study the underlying mechanisms of sodium channel clustering and will discuss the pathology of neurons in demyelinating disorders such as Multiple Sclerosis.

Poliak, S., and E. Peles. "The Local Differentiation of Myelinated Axons at Nodes of Ranvier." Nat Rev Neurosci 4, no. 12 (December 2003): 968-80. Review.

Waxman, S. G., M. J. Craner, and J. A. Black. "Na+ Channel Expression along Axons in Multiple Sclerosis and its Models." Trends Pharmacol Sci 25, no. 11 (November 2004): 584-91. Review.

Waxman, S. G. "Axonal Conduction and Injury in Multiple Sclerosis: The Role of Sodium Channels." Nat Rev Neurosci 7, no. 12 (December 2006): 932-41. Review.

Schizophrenia is a subtle disorder of brain development and synaptic function affecting 0.5-1% of the population worldwide. It is devastating in that it interferes with most basic cognitive processes: perception, emotion and judgment. An intriguing finding concerning the neuropathology of schizophrenia is that there is a reduction in the myelin content of the brain region associated with higher-order cognitive functions (i.e. the prefrontal cortex) and a misregulation of genes involved in myelination. Schizophrenia is a complex disease with multiple contributing genes and neurogulin-1 and its receptor erbB4 are two candidate genes linked to schizophrenia susceptibility. Data from diverse populations suggest that polymorphisms within the 5'-end of neuregulin-1 gene might lead to altered expression of the gene. This week we will discuss signaling pathways governed by Neuregulin-1 (NRG1) and its receptor erbB4, and how dysregulation of the NRG1-erbB4 signaling relates to the neuropathology of schizophrenia.

Freedman, R. "Schizophrenia." N Engl J Med 349, no. 18 (October 30, 2003): 1738-49. Review.

Morrison, P. D., and R. M. Murray. "Schizophrenia." Curr Biol 15, no. 24 (December 20, 2005): R980-4. Review.

Nave, K. A., and J. L. Salzer. "Axonal Regulation of Myelination by Neuregulin 1." Curr Opin Neurobiol 16, no. 5 (October 2006): 492-500. Review.

Corfas, G., K. Roy, and J. D. Buxbaum. "Neuregulin 1-erbB Signaling and the Molecular/Cellular Basis of Schizophrenia." Nat Neurosci 7, no. 6 (June 2004): 575-80. Review.

Ross, C. A., R. L. Margolis, S. A. Reading, M. Pletnikov, and J. T. Coyle. "Neurobiology of Schizophrenia." Neuron 52, no. 1 (October 5, 2006): 139-53. Review.

Taveggia, C., G. Zanazzi, A. Petrylak, H. Yano, J. Rosenbluth, S. Einheber, X. Xu, R. M. Esper, J. A. Loeb, P. Shrager, M. V. Chao, D. L. Falls, L. Role, and J. L. Salzer. "Neuregulin-1 type III Determines the Ensheathment Fate of Axons." Neuron 47, no. 5 (September 2005): 681-94.

Kondziella, D., E. Brenner, E. M. Eyjolfsson, and U. Sonnewald. "How Do Glial-Neuronal Interactions Fit Into Current Neurotransmitter Hypotheses of Schizophrenia?" Neurochem Int 50, no. 2 (January 2007): 291-301.

Astrocytes are the second most common glia in the central nervous system. They have long been regarded as either merely providing nutritional support for neurons or serving as boundary elements functionally separating different regions of the brain. Within the past 20 years this view has been challenged by several findings, and astrocytes are now known as key players in neuromodulation, synaptogenesis, myelination and neurogenesis. In this session, we will discuss how astrocytes interact with oligodendrocytes to regulate myelination and how retroviruses can disrupt this interaction leading to demyelination in diseases such as Multiple Sclerosis.

Franklin, R. J. "Why Does Remyelination Fail in Multiple Sclerosis?" Nat Rev Neurosci 3, no. 9 (September 2002): 705-14. Review.

Fields, R. D., and G. Burnstock. "Purinergic Signalling in Neuron-Glia Interactions." Nat Rev Neurosci 7, no. 6 (June 2006): 423-36. Review.

Haydon, P. G. "GLIA: Listening and Talking to the Synapse." Nat Rev Neurosci 2, no. 3 (March 2001): 185-93. Review.

Demerens, C., B. Stankoff, M. Logak, P. Anglade, B. Allinquant, F. Couraud, B. Zalc, and C. Lubetzki. "Induction of Myelination in the Central Nervous System by Electrical Activity." Proc Natl Acad Sci U S A 93, no. 18 (September 3, 1996): 9887-92.

Stevens, B., and R. D. Fields. "Response of Schwann Cells to Action Potentials in Development." Science 287, no. 5461 (March 24, 2000): 2267-71.

Abnormal synchronous neuronal activity is a hallmark of epilepsy. In postmortem epileptic brains, astrocytes display altered morphology and altered expression of proteins associated with their function. However, how astrocytes contribute to epilepsy is still debated. This week, we will discuss the developmental and functional contributions of astrocytes to epilepsy.

McNamara, J. O., Y. Z. Huang, and A. S. Leonard. "Molecular Signaling Mechanisms Underlying Epileptogenesis." Sci STKE 2006, no. 356 (October 10, 2006): re12. Review.

Glial and neuronal cells derive from common progenitor cells during development. Dysregulation of the signaling pathways in glia may result in tumorigenesis within the brain. Although they occur rare among all known malignant tumor, glial brain tumors are extremely hard to treat and can cause lethality within months after diagnosis. This week we are going to learn how brain tumor cells bear similarities to normal neurons and glia. Learning about physiological properties of glial tumor cells may help specific drug design for treatment of this devastating disease of glioblastoma.

Zhu, Y., and L. F. Parada. "The Molecular and Genetic Basis of Neurological Tumours." Nat Rev Cancer 2, no. 8 (August 2002): 616-26. Review.

Anderson, C. M., and R. A. Swanson. "Astrocyte Glutamate Transport: Review of Properties, Regulation, and Physiological Functions." Glia 32, no. 1 (October 2000): 1-14. Review.