F A C U L T Y   P R O F I L E 

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KANDEL, ERIC R., M.D.
Professor of Physiology & Cellular Biophysics, Biochemistry & MolecularBiophysics, and Psychiatry

Cellular and molecular mechanisms of associative and non-associative learning.

Office: P.I. Annex | 6th floor | Room 664
Telephone: 646.774.6825
Fax: 212.543.5474
Email:
erk5@columbia.edu

Current Research

Cellular and Molecular Mechanisms of Associative and Non-associative Learning

We combine behavioral, cellular, and molecular biological approaches to delineate the changes that underlie simple forms of learning and memory in invertebrates and vertebrates. In invertebrates the focus of our research is on the gill-withdrawal reflex of Aplysia. We study three elementary forms of learning: habituation, sensitization, and classical conditioning. Recently we have reconstituted critical components of this learning in dissociated cell culture, and we now use the reconstituted system to examine the molecular mechanisms, which contribute to short-and long-term memory. In vertebrates we use genetically modified mice to examine the mechanisms of long-term potentiation in the mammalian hippocampus and its relation to spatial memory and maintenance.


Selected Publications

Kandel ER, Dadai Y, Mayford MR. (2014) The Molecular and Systems Biology of Memory. Cell 157: 163-186.

Simpson EH, Morud J, Winiger V, Biezonskin D, Zhu JP, Bach ME, Malleret G, Polan HJ, Ng-Evans S, Phillips PEM, Kellendonk C, Kandel ER. (2014) Genetic variation in COMT activity impacts learning and dopamine release capacity in the striatum. Learn Mem 21:205-214.

Huang YY, Levine A, Kandel DB, Yin D, Colnaghi L, Drisaldi B, Kandel ER. (2014) D1/D5 receptors and histone deacetylation mediate the Gateway Effect of LTP in hippocampal dentate gyrus. Learn Mem 21: 153-60.

Pavlopoulos E, Jones S, Kosmidis S, Close M, Kim C, Kovalerchik O, Small SA, Kandel ER. Molecular mechanism for age-related memory loss: the histone-binding protein RbAp48. (2013) Sci Transl Med 5:200ra115.

Rajasethupathy P, Antonov I, Sheridan R, Frey S, Sander C, Tuschl T, Kandel ER. (2012) A Role for Neuronal piRNAs in the Epigenetic Control of Memory-Related Synaptic Plasticity. Cell 149: 693-707.

Levine A, Huang Y, Drisaldi B, Griffin EA Jr, Pollak DD, Xu S, Yin D, Schaffran C, Kandel DB, Kandel ER. (2011) Molecular mechanism for a gateway drug: epigenetic changes initiated by nicotine prime gene expression by cocaine. Sci Transl Med 3: 107ra109.

Antonov, I., Kandel, E.R., and Hawkins, R.D. (2010) Presynaptic and postsynaptic mechanisms of synaptic plasticity and metaplasticity during intermediate-term memory formation in Aplysia. Journal of Neuroscience 30(16)5781-5791.

Malleret G, Alarcon JM, Martel G, Takizawa S, Vronskaya S, Yin D, Chen IZ, Kandel ER, Shumyatsky GP. (2010) Bidirectional regulation of hippocampal long-term synaptic plasticity and its influence on opposing forms of memory. Journal of Neuroscience 30: 3813-25.

Jung, S.Y., Kim, J., Kwon, O. B., Jung, J. H., An, K., Jeong, A.Y., Lee, C. J., Choi, Y. B., Bailey, C. H., Kandel, E. R., and Kim, J. H. (2010) Input-specific synaptic plasticity in the amygdala is regulated by neuroligin-1 via postsynaptic NMDA receptors. PNAS 107:4710-4715.

Simpson, E.H., Kellendonk, C., and Kandel, E.R. (2010) A possible role for the striatum in the pathogenesis of the cognitive symptoms of schizophrenia. Neuron 65:585-596.

Si, K., Choi, Y., White-Grindley, E., Majumbar, A., and Kandel, E.R. (2010). Aplysia CPEB can form prion-like multimers in sensory neurons that contribute to long-term facilitation. Cell 140:421-435.

Rajasethupathy, P., Fiumara, F., Sheridan, R., Betel, D., Puthanveettil, S.V., James J. Russo, J.J., Sander, C., Tuschl, T., and Kandel, E.R. (2009) Characterization of small RNAs in Aplysia reveals a role for miR-124 in constraining long-term synaptic plasticity through CREB. Neuron 66(6):803-817.

Li, H-L., Huang, B.S., Vishwasrao, H., Sutedja, N., Chen, W., Jin, I., Hawkins, R.D., Bailey, C.H., and Kandel, E.R. (2009) Dscam meditates remodeling of glutamate receptors in Aplysia during de novo and learning-related synapse formation. Neuron 61(4):527-540.

Saxe, M.D., Malleret, G., Vronskaya, S., Mendez, I., Garcia, A.D., Sofroniew, M.V., Kandel, E.R., and Hen, R. 2007. Paradoxical influence of hippocampal neurogenesis on working memory. PNAS 104:4642-4646.

Touzani, K., Puthanveettil, S.V., and Kandel, E.R. 2007. Consolidation of learning strategies during spatial working memory task requires synthesis in the prefrontal cortex. PNAS 104:5632-5637.

Huang, Y-Y., and Kandel, E.R. 2007. 5-Hydroxytryptamine induces a protein kinase A/mitogen-activated protein kinase-mediated and macromolecular synthesis-dependent late phase of long-term potentiation in the amygdala. J Neurosci 27(12):3111-3119.

Lee, S.H, Lim, C.S, Park, H., Lee, J.A., Han, J.H., Kim, H., Cheang, Y.H., Lee, SH., Lee, Y.S., Ko, H.G., Jang, D.H., Kim, H., Miniaci, M.C., Bartsch, D., Kim, E., Bailey, C.H., Kandel, E.R., and Kaang, B.K. 2007. Nuclear translocation of CAM-associated protein activates transcription for long-term facilitation in Aplysia. Cell 129:801-812.

Huang, Y.Y., and Kandel, E.R. 2007. Low-frequency stimulation induces a pathway-specific late phase of LTP in the amygdala that is mediated by PKA and dependent on protein synthesis. Learn Mem 14:497-503.

Drew, M.R., Simpson, E.H., Kellendonk, C., Herzberg, W.G., Lipatova, O., Fairhurst, S., Kandel, E.R., Malapani, C., and Balsam, P.D. 2007. Transient overexpression of striatal D2 receptors impairs operant motivation and interval timing. J Neurosci 27(29):7731-7739.

Mayford, M., Mansuy, I.M., Muller, R.U., and Kandel, E.R. 1997. Memory and behavior: a second generation of genetically modified mice. Current Biology, 7:R580-R589.

Martin K.C., Casadio, A., Zhu, H., E.Y., Rose, J.C., Chen, M., Bailey, C.H., and Kandel, E.R. 1997. Synapse-specific, long-term facilitation of Aplysia sensory to motor synapses: A function for local protein synthesis in memory storage. Cell, 91:927-938.

Antonov, I., Kandel, E.R., and Hawkins, R.D. (2010) Presynaptic and postsynaptic mechanisms of synaptic plasticity and metaplasticity during intermediate-term memory formation in Aplysia. Journal of Neuroscience 30(16)5781-5791.

Malleret G, Alarcon JM, Martel G, Takizawa S, Vronskaya S, Yin D, Chen IZ, Kandel ER, Shumyatsky GP. Bidirectional regulation of hippocampal long-term synaptic plasticity and its influence on opposing forms of memory. Journal of Neuroscience 30: 3813-25.

Jung, S.Y., Kim, J., Kwon, O. B., Jung, J. H., An, K., Jeong, A.Y., Lee, C. J., Choi, Y. B., Bailey, C. H., Kandel, E. R., and Kim, J. H. (2010) Input-specific synaptic plasticity in the amygdala is regulated by neuroligin-1 via postsynaptic NMDA receptors. PNAS 107:4710-4715.

Simpson, E.H., Kellendonk, C., and Kandel, E.R. (2010) A possible role for the striatum in the pathogenesis of the cognitive symptoms of schizophrenia. Neuron 65:585-596.

Si, K., Choi, Y., White-Grindley, E., Majumbar, A., and Kandel, E.R. (2010). Aplysia CPEB can form prion-like multimers in sensory neurons that contribute to long-term facilitation. Cell 140:421-435.

Rajasethupathy, P., Fiumara, F., Sheridan, R., Betel, D., Puthanveettil, S.V., James J. Russo, J.J., Sander, C., Tuschl, T., and Kandel, E.R. (2009) Characterization of small RNAs in Aplysia reveals a role for miR-124 in constraining long-term synaptic plasticity through CREB. Neuron 66(6):803-817.

Li, H-L., Huang, B.S., Vishwasrao, H., Sutedja, N., Chen, W., Jin, I., Hawkins, R.D., Bailey, C.H., and Kandel, E.R. (2009) Dscam meditates remodeling of glutamate receptors in Aplysia during de novo and learning-related synapse formation. Neuron 61(4):527-540.

Saxe, M.D., Malleret, G., Vronskaya, S., Mendez, I., Garcia, A.D., Sofroniew, M.V., Kandel, E.R., and Hen, R. 2007. Paradoxical influence of hippocampal neurogenesis on working memory. PNAS 104:4642-4646.

Touzani, K., Puthanveettil, S.V., and Kandel, E.R. 2007. Consolidation of learning strategies during spatial working memory task requires synthesis in the prefrontal cortex. PNAS 104:5632-5637.

Huang, Y-Y., and Kandel, E.R. 2007. 5-Hydroxytryptamine induces a protein kinase A/mitogen-activated protein kinase-mediated and macromolecular synthesis-dependent late phase of long-term potentiation in the amygdala. J Neurosci 27(12):3111-3119.

Lee, S.H, Lim, C.S, Park, H., Lee, J.A., Han, J.H., Kim, H., Cheang, Y.H., Lee, SH., Lee, Y.S., Ko, H.G., Jang, D.H., Kim, H., Miniaci, M.C., Bartsch, D., Kim, E., Bailey, C.H., Kandel, E.R., and Kaang, B.K. 2007. Nuclear translocation of CAM-associated protein activates transcription for long-term facilitation in Aplysia. Cell 129:801-812.

Huang, Y.Y., and Kandel, E.R. 2007. Low-frequency stimulation induces a pathway-specific late phase of LTP in the amygdala that is mediated by PKA and dependent on protein synthesis. Learn Mem 14:497-503.

Drew, M.R., Simpson, E.H., Kellendonk, C., Herzberg, W.G., Lipatova, O., Fairhurst, S., Kandel, E.R., Malapani, C., and Balsam, P.D. 2007. Transient overexpression of striatal D2 receptors impairs operant motivation and interval timing. J Neurosci 27(29):7731-7739.
Mayford, M., Mansuy, I.M., Muller, R.U., and Kandel, E.R. 1997. Memory and behavior: a second generation of genetically modified mice. Current Biology, 7:R580-R589.

Martin K.C., Casadio, A., Zhu, H., E.Y., Rose, J.C., Chen, M., Bailey, C.H., and Kandel, E.R. 1997. Synapse-specific, long-term facilitation of Aplysia sensory to motor synapses: A function for local protein synthesis in memory storage. Cell, 91:927-938.