Areas of Interest

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 is being used as a model system. 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.

A variety of molecular, biochemical, biophysical, electrophysiological and imaging techniques are used to analyze the properties of the neural circuits and the individual neurons.

The empirical analyses are complemented with realistic mathematical modeling in order to determine the extent to which the observed processes and their interactions are sufficient to explain the behavior of the system.

Schematic Representation of a Neural Circuit

 

Publications

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Selected Papers from PubMed

  • 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.
  • Lorenzetti, F.D., Baxter, D.A. and Byrne, J.H.  Molecular mechanisms underlying a cellular analogue of operant reward learning.  Neuron, 59: 815-828, 2008.   NIHMSID # 70417.
  • Mozzachiodi, R., Lorenzetti, F.D., Baxter, D.A., and Byrne, J.H.  Changes in neuronal excitability serve as a mechanism of long-term memory for operant conditioning. Nature Neuroscience, 11:1146-1148, 2008.
  • Fioravante, D., Liu, R.Y. and Byrne, J.H.  The ubiquitin-proteasome system is necessary for long-term synaptic depression in Aplysia. J. Neuroscience.28:10245-10256, 2008. NIHMSID # 72703.
  • Mozzachiodi, R. and Byrne, J.H. More than synaptic plasticity: Role of nonsynaptic plasticity in learning and memory. Trends in Neurosciences 33:17-26, 2010.  NIHMS #157344, PMID 19889466.
  • Zhang, Y., Smolen, P.D., Baxter, D.A. and Byrne, J.H.  The sensitivity of memory consolidation and reconsolidation to inhibitors of protein synthesis and kinases:  Computational analysis.  Learning and Memory, 17: 428-439, 2010.
  • Liu, R.Y., Shah, S., Cleary, L.J. and Byrne, J.H.  Serotonin- and training-induced dynamic regulation of CREB2 in Aplysia. Learning and Memory, 18:245-249, 2011.
  • Liu, R.Y., Cleary, L.J. and Byrne, J.H.  The requirement for enhanced CREB1 expression in consolidation of long-term synaptic facilitation and long-term excitability in sensory neurons of Aplysia. J. Neuroscience, 31:6871-6879, 2011.
  • Lorenzetti, F.D., Baxter, D.A. and Byrne, J.H.  Classical conditioning analog enhanced acetylcholine responses but reduced excitability of an identified neuron.  J. Neuroscience, 31:14789-14793, 2011. PMCID: PMC3198865.
  • Hart, A.K., Fioravante, D., Liu, R.Y., Phares, G.A., Cleary, L.J., and Byrne, J.H. Serotonin-mediated synapsin expression is necessary for long-term facilitation of the Aplysia sensorimotor synapse. J. Neuroscience, 31:18401-1841, 2011. PMID#22171042, NIHMSID#347966.
  • Zhang, Y., Liu, R.Y., Heberton, G.A., Smolen, P.D., Baxter, D.A., Cleary, L.J. and Byrne, J.H.  Computational design of enhanced learning protocols Nature Neuroscience, 15:294-297, 2012. PMID#22197829.
  • Liu, R.Y., Zhang, Y., Baxter, D.A. Smolen, P., Cleary, L.J. and Byrne, J.H. Deficit in long-term synaptic plasticity is rescued by a computationally predicted stimulus protocol. J. Neuroscience, 33:6944-6949, 2013.
  • Liu, R.Y., Zhang, Y. Coughlin, B., Cleary, L. and Byrne, J.H. Doxorubicin attenuates serotonin-induced long-term synaptic facilitation by phosphorylation of p38 mitogen-activated protein kinase. J. Neuroscience, 34:13289-13300, 2014. PMCID: PMC4180468.
  • Byrne, J.H. and Hawkins, R.D.  Nonassociative learning in invertebrates.  Cold Spring Harbor Perspectives in Biology, 7:a021675, 2015.  PMCID: PMC4448621.
  • Hawkins, R.D. and Byrne, J.H.  Associative learning in invertebrates.  Cold Spring Harbor Perspectives in Biology, 7:a021709, 2015.  PMCID: PMC4448622.
  • Smolen, P., Zhang, Y. and Byrne, J.H. The right time to learn: mechanisms and optimization of spaced learning. Nature Reviews Neuroscience, 17:77-88, 2016. PMCID: PMC5126970.
  • Smolen, P., Baxter, D.A. and Byrne, J.H. How can memories last for days, years, or a lifetime? Proposed mechanisms for maintaining synaptic potentiation and memory. Learning & Memory, 26: 133-150, 2019. PMID: 30992383.
  • Liu, R.Y., Zhang, Y., Smolen, P., Cleary, L.J. and Byrne, J.H.  Role of p90 ribosomal S6 kinase in long-term synaptic facilitation and enhanced neuronal excitability.  Scientific Reports, 10: 608, 2020. doi: 10.1038/s41598-020-57484-y, PMID: 31953461.
  • Costa, R.M., Baxter, D.A. and Byrne, J.H.. Computational model of the distributed representation of operant reward memory: Combinatoric engagement of intrinsic and synaptic plasticity mechanisms.  Learning & Memory, 27:236-249, 2020. PMID: 32414941.
  • Smolen P., Wood M.A., Baxter D.A., and Byrne J.H. Modeling suggests combined-drug treatments for disorders impairing synaptic plasticity via shared signaling pathways.  Journal of Computational Neuroscience, 2020. DOI 10.1007/s10827-020-00771-4.
  • Smolen P., Baxter D.A., and Byrne J.H. Comparing theories for the maintenance of late LTP and long-term memory: Computational analysis of the roles of kinase feedback pathways and synaptic reactivation. Frontiers in Computational Neuroscience. 2020. DOI 10.3389/fncom.2020.569349.
  • Young, J., Neveu, C. L., Byrne, J. H., Aazhang, B. Inferring functional connectivity through graphical directed information. Journal of Neural Engineering, 18 046019. https://doi.org/10.1088/1741-2552/abecc6. 2021. PMID: 33684898.
  • Costa, R.M., Baxter, D.A., and Byrne, J.H. Neuronal population activity dynamics reveal a low-dimensional signature of operant learning in Aplysia. Communications Biology, 5:90, 2022. PMID: 35075264.
  • Momohara, Y., Neveu, C.L., Chen, H-M., Baxter, D.A. and Byrne, J.H. Specific plasticity loci and their synergism mediate operant conditioning. Journal of Neuroscience, 42:1211-1223, 2022. PMID: 34992131.
  • Zhang Y, Smolen P, Alberini CM, Baxter DA, and Byrne JH. Computational analysis of memory consolidation following inhibitory avoidance (IA) training in adult and infant rats: Critical roles of CaMKIIα and MeCP2.  PLOS Computational Biology, 2022 Jun 27;18(6):e1010239. doi: 10.1371/journal.pcbi.1010239. eCollection 2022 Jun. PMID: 35759520.
  • Zhang, Y., Liu, R-Y., Smolen, P., Cleary, L.J., and Byrne, J. H. Dynamics and mechanisms of ERK activation after different protocols that induce long-term synaptic facilitation in Aplysia. Oxford Open Neuroscience, 2: 1-12, 2023, doi.org/10.1093/oons/kvac014.
  • Zhang, X.O., Zhang, Y., Cho, C.E., Engelke, D.S., Smolen P., Byrne, J.H., Do-Monte, F.H. Enhancing associative learning in rats with a computationally designed training protocol. Biological Psychiatry: Global Open Science, https://doi.org/10.1016/j.bpsgos.2023.07.006.
  • Neveu, C.L., Baxter, D.A. and Byrne, J.H. Voltage- and calcium-gated membrane currents tune the plateau potential properties of multiple neuron types. Journal of Neuroscience, 43:7601-7615.  doi: 10.1523/JNEUROSCI.0789-23.2023. PMID: 37699717.
  • Byrne, J.H. Autobiography.  In: The History of Neuroscience in Autobiography, Volume 13, eds., T. D. Albright and L. R. Squire, Society for Neuroscience, pp. 144-193, https://doi.org/10.1523/hon.013004, 2024.