The Department of Neurobiology and Anatomy - The University of Texas Medical School at Houston
Department of Neurobiology and Anatomy
The Department ofNeurobiology

John H. Byrne, Ph.D.

June and Virgil Waggoner Chair
Chairman, Department of Neurobiology and Anatomy
Telephone: 713.500.5602
E-mail: john.h.byrne@uth.tmc.edu


 

Neural And Molecular Bases Of Learning And Memory

John H. Byrne, Ph.D. - Department ChairmanThe 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.

Selected Reading

Byrne, JH, Kandel, ER. (1996) Presynaptic facilitation revisited: State and time dependence. J. Neuroscience, 16(2): 425-435.

Zhang, F, Endo, S, Cleary, LJ, Eskin, A, Byrne, JH. (1997) Role of transforming growth factor-ß in long-term synaptic facilitation in Aplysia. Science, 275:1318-1320.

Smolen, P, Baxter, DA, Byrne, JH. (2000) Mathematical modeling of gene networks. Neuron, 26:567-580.

Brembs, B, Lorenzetti, FD, Reyes, FD, Baxter, DA, Byrne, JH. (2002) Operant reward learning in Aplysia: Neuronal correlates and mechanisms. Science, 296:1706-1709.

Angers, A, Fioravante, D, Chin, J, Cleary, LJ, Bean, AJ, Byrne, JH. (2002) Serotonin stimulates phosphorylation of Aplysia synapsin and alters its subcellular distribution in sensory neurons. J. Neurosci., 22:5412-5422.

Mohamed, HA, Yao, W, Fioravante, D, Smolen, P, Byrne, JH. (2005)  cAMP-response elements in Aplysia creb1, creb2, and Ap-uch promoters. Journal of Biological Chemistry, 280: 27035-27043.

Smolen, P, Baxter, DA, Byrne, JH. (2006) A model of the roles of essential kinases in the induction and expression of late long-term potentiation.  Biophysical Journal, 90:2760-2775.

Fukushima, T, Liu, RY, Byrne, JH. (2007) Transforming growth factor-β2 modulates synaptic efficacy and plasticity and induces phosphorylation of CREB in hippocampal neurons.  Hippocampus, 17:5-9.

Antzoulatos, EG, Byrne, JH. (2007) Long-term sensitization training produces spike narrowing in Aplysia sensory neurons.  J. Neuroscience, 27:676-683.

Song, H, Smolen, P, Av-Ron, E, Baxter, DA, Byrne, JH. (2007) 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.

Fioravante, D, Liu, RY, Netek, A, Cleary, LJ, Byrne, JH. (2007) Synapsin regulates basal synaptic strength, synaptic depression and serotonin-induced facilitation of sensorimotor synapses in Aplysia.  J. Neurophysiology, 98:3568-3580.

Smolen, P, Baxter, DA, Byrne, JH. (2008) Bistable MAP kinase activity: a plausible mechanism contributing to maintenance of late long-term potentiation.  Am. J. of Physiology-Cell Physiology, 294: C503–C515.

Liu, RY, Fioravante, D, Shah, S, Byrne, JH. (2008) CREB1 feedback loop is necessary for consolidation of long-term synaptic facilitation in Aplysia.  J. Neuroscience, 28: 1970-1976.

Lorenzetti, F.D., Baxter, D.A., Byrne, J.H.  Molecular mechanisms underlying a cellular analogue of operant reward learning.  Neuron, in press.

Mozzachiodi, R., Lorenzetti, F.D., Baxter, D.A., Byrne, J.H.  Changes in neuronal excitability serve as a mechanism of long-term memory for operant conditioning. Nature Neuroscience, in press.

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