In Search of Memory: The Emergence of a New Science of Mind (58 page)

Castellucci, V., and E. R. Kandel. “Presynaptic facilitation as a mechanism for behavioral sensitization in
Aplysia.” Science
194 (1976): 1176–78.

Dale, N., and E. R. Kandel. “L-glutamate may be the fast excitatory transmitter of
Aplysia
sensory neurons.”
Proc. Nat. Acad. Sci. USA
90 (1993): 7163–67.

Jacob, F.
The Possible and the Actual
. New York: Pantheon, 1982; quotation from pp. 33–35.

———.
The Statue Within
. Translated by F. Philip. New York: Basic Books, 1988.

Kandel, E. R.
Cellular Basis of Behavior: An Introduction to Behavioral Neurobiology
. San Francisco: Freeman, 1976.

Kandel, E. R., M. Klein, B. Hochner, M. Shuster, S. Siegelbaum, R. Hawkins, D. Glanzman, V. F. Castellucci, and T. Abrams. “Synaptic modulation and learning: New insights into synaptic transmission from the study of behavior.” In
Synaptic
Function
, edited by G. M. Edelman, W. E. Gall, and W. M. Cowan, 471–518. New York: John Wiley & Sons, 1987.

Kistler, H. B., Jr., R. D. Hawkins, J. Koester, H. W. M. Steinbusch, E. R. Kandel, and J. H. Schwartz. “Distribution of serotonin-immunoreactive cell bodies and processes in the abdominal ganglion of mature
Aplysia.” J. Neurosci.
5 (1985): 72–80.

Kriegstein, A., V. F. Castellucci, and E. R. Kandel. “Metamorphosis of
Aplysia californica
in laboratory culture.”
Proc. Nat. Acad. Sci. USA
71 (1974): 3654–58.

Kuffler, S., and J. Nicholls.
From Neuron to Brain: A Cellular Approach to the Function of the Nervous System
. Sunderland, Mass.: Sinauer Associates, 1976.

Siegelbaum, S., J. S. Camardo, and E. R. Kandel. “Serotonin and cAMP close single K
⁺
channels in
Aplysia
sensory neurons.”
Nature
299 (1982): 413–17.

17: Long-Term Memory

François Jacob writes about day versus night science in
The Statue Within
, trans. F. Philip (New York: Basic Books, 1988), pp. 296–97.

For a discussion of Thomas Hunt Morgan, see two biographies: G. E. Allen,
Thomas Hunt Morgan: The Man and His Science
(Princeton, N.J.: Princeton University Press, 1978); and A. H. Sturtevant,
Thomas Hunt Morgan
(New York: National Academy of Sciences, 1959). See also E. R. Kandel, “Thomas Hunt Morgan at Columbia: Genes, chromosomes, and the origins of modern biology,” pp. 29–35, and E. R. Kandel, “An American century of biology,” pp. 36–39, both in
Living Legacies: Great Moments in the Life of Columbia for the 250th Anniversary
, fall 1999 issue of
Columbia: The Magazine
of
Columbia University
.

Watson and Crick first announced their findings in “Molecular structure of nucleic acids: A structure of deoxyribose nucleic acid,”
Nature
171 (1953): 737–38; quotation from p. 738. See also J. D. Watson and F. H. C. Crick, “Genetical implications of the structure of deoxyribonucleic acid,”
Nature
171 (1953): 964–67; J. D. Watson,
The Double Helix
(1968; reprint, New York: Touchstone/Simon & Schuster, 2001); and J. D. Watson and A. Berry,
DNA: The Secret of Life
(New York: Alfred A. Knopf, 2003). The latter book is the source for Watson’s reflections (p. 88). Schrödinger’s essay appeared in E. Schrödinger,
What Is Life? The Physical Aspect of the Living Cell
. 1944. (Reprint, Cambridge: Cambridge University Press, 1947).

Other information for this chapter was drawn from the following:

Avery, O. T., C. M. MacLeod, and M. McCarty. “Studies on the chemical nature of the substance inducing transformation of pneumococcal types: Induction of transformation by a desoxyribonucleic acid fraction isolated from Pneumococcus Type III.”
J. Exp. Med
. 79 (1944): 137–58.

Chimpanzee Genome
. Special issue on chimpanzees.
Nature
437, September 1, 2005.

Cohen, S. N., A. C. Chang, H. W. Boyer, and R. B. Helling. “Construction of biologically functional bacterial plasmids
in vitro.” Proc. Natl. Acad. Sci. USA
70, no. 11 (1973): 3240–44.

Crick, F. H., L. Barnett, S. Brenner, and R. J. Watts-Tobin. “General nature of the genetic code for proteins.”
Nature
192 (1961): 1227–32.

Gilbert, W. “DNA sequencing and gene structure.”
Science
214 (1981): 1305–12.

Jackson, D. A., R. H. Symons, and P. Berg. “Biochemical method for inserting new genetic information into DNA Simian Virus 40: circular SV40 DNA molecules containing lambda phage genes and the galactose operon of
Escherichia coli.” Proc. Nat. Acad. Sci. USA
69 (1972): 2904–09.

Jessell, T. M., and E. R. Kandel. “Synaptic transmission: A bidirectional and a self-modifiable form of cell-cell communication.”
Cell 72/Neuron 10
(Suppl.) (1993): 1–30.

Matthaei, H., and M. W. Nirenberg. “The dependence of cell-free protein synthesis in
E. coli
upon RNA prepared from ribosomes.”
Biochem. Biophys. Res. Commun. 4
(1961): 404–8.

Sanger, F. “Determination of nucleotide sequences in DNA.”
Science
214 (1981): 1205–10.

18: Memory Genes

Jacob and Monod’s classic paper is F. Jacob and J. Monod, “Genetic regulatory mechanisms in the synthesis of proteins,”
J. Molec. Biol.
3 (1961): 318–56.

Other information in this chapter was drawn from the following:

Buck, L., and R. Axel. “Novel multigene family may encode odorant receptors: A molecular basis for odor recognition.”
Cell
65, no. 1 (1991): 175–87.

Jacob, F.
The Statue Within.
Translated by F. Philip. New York: Basic Books, 1988.

Kandel, E. R., A. Kriegstein, and S. Schacher. “Development of the central nervous system of
Aplysia
in the terms of the differentiation of its specific identifiable cells.”
Neurosci.
5 (1980): 2033–63.

Scheller, R. H., J. F.Jackson, L. B. McAllister, J. H. Schwartz, E. R. Kandel, and R. Axel. “A family of genes that codes for ELH, a neuropeptide eliciting a stereotyped pattern of behavior in
Aplysia.” Cell
28 (1982): 707–19; quotation from p. 707.

Weinberg, R. A.
Racing to the Beginning of the Road: The Search for the Origin of Cancer.
San Francisco: Freeman, 1998; quotation from pp. 162–63.

19: A Dialogue Between Genes and Synapses

The two reviews by Phillip Goelet are P. Goelet, V. F. Castellucci, S. Schacher, and E. R. Kandel, “The long and short of long-term memory—a molecular framework,”
Nature
322 (1986): 419–22; and P. Goelet and E. R. Kandel, “Tracking the flow of learned information from membrane receptors to genome,”
Trends Neurosci.
9 (1986): 472–99.

In the experiments on the translocation of the cAMP-dependent protein kinase, we collaborated with Roger Tsien, a Howard Hughes investigator at the University of California, San Diego, who developed the method we used to visualize the movement of the cAMP-dependent protein kinase to the nucleus. This work is described in B. J. Bacskai, B. Hochner, M. Mahaut-Smith, S. R. Adams, B.-K. Kaang, E. R. Kandel, and R. Y. Tsien, “Spatially resolved dynamics of cAMP and protein kinase A subunits in
Aplysia
sensory neurons,”
Science
260 (1993): 222–26.

The development of tissue culture methods for the
Aplysia
neuron was initiated by Sam Schacher in collaboration with my students Stephen Rayport, Pier Giorgio Montarolo, and Eric Proshansky.

The initial evidence for CREB in learning-related plasticity is in P. K. Dash, B. Hochner, and E. R. Kandel, “Injection of cAMP-responsive element into the nucleus of
Aplysia
sensory neurons blocks long-term facilitation,”
Nature
345 (1990): 718–21.

The finding of a repressor in
Aplysia
is described in D. Bartsch, M. Ghirardi, P. A. Skehel, K. A. Karl, S. P. Herder, M. Chen, C. H. Bailey, and E. R. Kandel, “
Aplysia
CREB-2 represses long-term facilitation: Relief of repression converts transient facilitation into long-term functional and structural change,”
Cell
83 (1995): 979–92.

For the new protocol to study memory in
Drosophila,
see T. Tully, T. Preat, S. C. Boynton, and M. Del Vecchio, “Genetic dissection of consolidated memory in
Drosophila melanogaster,” Cell
79 (1994): 35–47.

The studies in
Drosophila
that pointed to the role of CREB repressor in blocking long-term memory and activator over-expressed in enhancing memory storage for learned fear is in J. C. P. Yin, J. S. Wallach, M. Del Vecchio, E. L. Wilder, H. Zhuo, W. G. Quinn, and T. Tully, “Induction of a dominant negative CREB transgene specifically blocks long-term memory in
Drosophila,” Cell
79 (1994): 49–58; J. C. P. Yin, M. Del Vecchio, H. Zhou, and T. Tully, “CREB as a memory modulator: Induced expression of a dCREB2 activator isoform enhances long-term memory in Drosophila.”
Cell
81 (1995): 107–15.

For evidence of CREB in the honeybee, see D. Eisenhardt, A. Friedrich, N. Stollhoff, U. Müller, H. Kress, and R. Menzel, “The
AmCREB
gene is an ortholog of the mammalian CREB/CREM family of transcription factors and encodes several splice variants in the honeybee brain,”
Insect Molecular Biol
. 12 (2003): 373–82.

The evidence for CREB in learned fear in the mouse is in P. W. Frankland, S. A. Josselyn, S. G. Anagnostaras et al., “Consolidation of CS and US representations in associative fear conditioning,”
Hippocampus
14 (2004): 557–69; and S. Kida, S. A. Josselyn, S. P. de Ortiz et al., “CREB required for the stability of new and reactivated fear memories,”
Nature Neurosci
. 5 (2002): 348–55.

For the evidence for CREB in human learning, see J. M. Alarcon, G. Malleret, K. Touzani, S. Vronskaya, S. Ishii, E. R. Kandel, and A. Barco, “Chromatin acetylation, memory, and LTP are impaired in CBP
^+/-
mice: A model for the cognitive deficit in Rubinstein-Taybi Syndrome and its amelioration,”
Neuron
42 (2004): 947–59.

Other information for this chapter was drawn from the following:

Bailey, C. H., P. Montarolo, M. Chen, E. R. Kandel, and S. Schacher. “Inhibitors of protein and RNA synthesis block structural changes that accompany long-term heterosynaptic plasticity in
Aplysia.” Neuron
9 (1992): 749–58.

Bartsch, D., A. Casadio, K. A. Karl, P. Serodio, and E. R. Kandel. “CREB-1 encodes a nuclear activator, a repressor, and a cytoplasmic modulator that form a regulatory unit critical for long-term facilitation.”
Cell 95
(1998): 211–23.

Bartsch, D., M. Ghirardi, A. Casadio, M. Giustetto, K. A. Karl, H. Zhu, and E. R. Kandel. “Enhancement of memory-related long-term facilitation by ApAF, a novel transcription factor that acts downstream from both CREB-1 and CREB-2.”
Cell
103 (2000): 595–608.

Casadio, A., K. C. Martin, M. Giustetto, H. Zhu, M. Chen, D. Bartsch, C. H. Bailey, and E. R. Kandel. “A transient neuron-wide form of CREB-mediated long-term facilitation can be stabilized at specific synapses by local protein synthesis.”
Cell
99 (1999): 221–37.

Chain, D. G., A. Casadio, S. Schacher, A. N. Hegde, M. Valbrun, N. Yamamoto, A. L. Goldberg, D. Bartsch, E. R. Kandel, and J. H. Schwartz. “Mechanisms for generating the autonomous cAMP-dependent protein kinase required for long-term facilitation in
Aplysia.” Neuron
22 (1999): 147–56.

Dale, N., and E. R. Kandel. “L-glutamate may be the fast excitatory transmitter of
Aplysia
sensory neurons.”
Proc. Natl. Acad. Sci. USA
90 (1993): 7163–67.

Glanzman, D. L., E. R. Kandel, and S. Schacher. “Target-dependent structural changes accompanying long-term synaptic facilitation in
Aplysia
neurons.”
Science
249 (1990): 799–802.

Kaang, B.-K., E. R. Kandel, and S. G. N. Grant. “Activation of cAMP-responsive genes by stimuli that produce long-term facilitation in
Aplysia
sensory neurons.”
Neuron
10 (1993): 427–35.