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John H. Byrne, Ph.D. 1973, Polytechnic Institute of Brooklyn UT-Houston Medical School |
Research Interests: Neural and molecular bases of learning and memory
The research interests of this laboratory are the neuronal and molecular mechanisms underlying learning and memory. The marine mollusc Aplysia californica and hippocampal cultures and slices are being used as model systems. In Aplysia we are studying mechanisms of implicit (nondeclarative) memory associated with simple forms of learning such as habituation, sensitization, classical or Pavlovian conditioning and operant conditioning. In hippocampal preparations we are studying mechanisms of explicit (declarative) memory associated with more complex learning processes such as remembering a place or how to solve a maze problem. As these studies progress, we will be able to compare and contrast learning rules and memory mechanisms among these different memory systems.
A variety of molecular, biochemical, biophysical, electrophysiological, imaging, and computer simulation techniques are used to analyze the properties of the neural circuits and the individual neurons. For example, with intracellular recording techniques we have found that simple forms of learning involve changes in synaptic transmission at existing synaptic connections. We have also determined that these changes are induced by the elevation of intracellular second messengers such as cAMP and DAG, which appear to act by modulating specific membrane channels and other cellular processes such as those associated with the machinery for transmitter release. We are now investigating how these processes are modulated both in the short-term of minutes by covalent modifications and in the long-term of days by growth factors and cAMP-induction of new gene transcription and protein synthesis. The empirical analyses are complemented with realistic mathematical modeling in order to determine whether the observed processes and their interactions are sufficient to explain the behavior of the system.
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Byrne, J.H. and Kandel, E.R. Presynaptic facilitation revisited: state- and time-dependence. J. Neuroscience 16:425-435, 1996.
Brembs, B., Lorenzetti, F.D., Reyes, F.D., Baxter, D.A. and Byrne, J.H. Operant reward learning in Aplysia: Neuronal correlates and mechanisms. Science 296:1706-1709, 2002.
Mohamed, H.A., Yao, W., Fioravante, D., Smolen, P.D., Byrne, J.H. cAMP-response elements in Aplysia creb1, creb2, and Ap-uch promoters. Journal of Biological Chemistry, 280:27035-27043, 2005.
Lorenzetti, F.D., Mozzachiodi, R., Baxter, D.A., Byrne, J.H. Classical and operant conditioning differentially modify the intrinsic properties of an identified neuron. Nature Neuroscience, 9:17-19, 2006.
Smolen, P.D., Baxter, D.A., and Byrne, J.H. A model of the roles of essential kinases in the induction and expression of late long-term potentiation. Biophysical Journal, 90:2760-2775, 2006.
Song, H., Smolen, P., Av-Ron, E., Baxter, D.A. and Byrne, J.H. Dynamics of a minimal model of interlocked positive and negative feedback loops of transcriptional regulation by cAMP-responsive element binding proteins. Biophysical Journal, 92:3407-3424, 2007
Liu, R.Y., Fioravante, D., Shah, S. and Byrne, J.H. CREB1 feedback loop is necessary for consolidation of long-term synaptic facilitation in Aplysia. J. Neuroscience, 28: 1970-1976, 2008.
Program Affiliation:
Program in Neuroscience