In Search of Memory: The Emergence of a New Science of Mind (57 page)

The environment at Harvard during the Kuffler period is well described in O. J. McMahan, ed.,
Steve: Remembrances of Stephen W. Kuffler
(Sunderland, Mass.: Sinauer Associates, 1990); and in D. H. Hubel and T. N. Wiesel,
Brain and Visual Reception
(Oxford: Oxford University Press, 2005).

The quote from Per Andersen is from P. Andersen, “A prelude to long-term potentiation,” in
LTP: Long-Term Potentiation
, edited by T. Bliss, G. Collingridge, and R. Morris (Oxford: Oxford University Press, 2004). The review that Alden Spencer and I wrote is in E. R. Kandel and W. A. Spencer, “Cellular neurophysiological approaches in the study of learning,”
Physiol. Rev.
48 (1968): 65–134.

13: Even a Simple Behavior Can Be Modified by Learning

Mapping of connections between identified cells is based on W. T. Frazier, E. R. Kandel, I. Kupfermann, R. Waziri, and R. E. Coggeshall, “Morphological and functional properties of identified neurons in the abdominal ganglion of
Aplysia californica.” J. Neurophysiol.
30 (1967): 1288–1351; E. R. Kandel, W. T. Frazier, R. Waziri, and R. E. Coggeshall, “Direct and common connections among identified neurons in
Aplysia,” J. Neurophysiol.
30 (1967): 1352–76; I. Kupfermann and E. R. Kandel, “Neuronal controls of a behavioral response mediated by the abdominal ganglion of
Aplysia,” Science
164 (1969): 847–50. In the initial experiments we often used shock to the head instead of tail for a strong unconditioned stimulus in sensitization experiments.

Other information for this chapter was drawn from the following:

Arvanitaki, A., and N. Chalazonitis. “Configurations modales de l’activité, propres à différents neurons d’un même centre.”
J. Physiol.
(Paris) 50 (1958): 122–25.

Byrne, J., V. Castellucci, and E. R. Kandel. “Receptive fields and response properties of mechanoreceptor neurons innervating siphon skin and mantle shelf of
Aplysia.” J. Neurophysiol.
37 (1974): 1041–64.

———. “Contribution of individual mechanoreceptor sensory neurons to defensive gill-withdrawal reflex in
Aplysia.” J. Neurophysiol.
41 (1978): 418–31.

Cajal, S. R. “The Croonian Lecture: La fine structure des centres nerveux.”
Proc. R. Soc. London Ser. B 55
(1894): 444–67.

Carew, T. J., R. D. Hawkins, and E. R. Kandel. “Differential classical conditioning of a defensive withdrawal reflex in
Aplysia californica.” Science
219 (1983): 397–400.

Goldschmidt, R. “Das nervensystem von Ascaris lumbricoides und megalocephala: Ein versuch in den aufhaus eines einfaches nervensystem enzudringen. Erster Teil. Z. Wiss.”
Zool.
90 (1908): 73–126.

Hawkins, R. D., V. F. Castellucci, and E. R. Kandel. “Interneurons involved in mediation and modulation of the gill-withdrawal reflex in
Aplysia
. II: Identified neurons produce heterosynaptic facilitation contributing to behavioral sensitization.”
J. Neurophysiol
. 45 (1981): 315–26.

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

———.
The Behavioral Biology of Aplysia: A Contribution to the Comparative Study of Opisthobranch Molluscs
. San Francisco: Freeman, 1979.

Köhler, W.
Gestalt Psychology. An Introduction to New Concepts of Modern Psychology.
Denver: Mentor Books/New American Library, 1947.

Pinsker, H., I. Kupfermann, V. Castellucci, and E. R. Kandel. “Habituation and dishabituation of the gill-withdrawal reflex in
Aplysia.” Science
167 (1970): 1740–42.

Thorpe, W. H.
Learning and Instinct in Animals
. Rev. ed. Cambridge, Mass.: Harvard University Press, 1963.

14: Synapses Change with Experience

For a discussion of Freud’s theories of synaptic plasticity and memory, see S. Freud, “Project for a scientific psychology,” in
Standard Edition
, trans. and ed. James Strachey et al., vol. 1, 281–397 (New York: W. W. Norton, 1976); K. H. Pribram and M. M. Gill,
Freud’s “Project” Re-assessed: Preface to Contemporary Cognitive Theory and Neuropsychology
(New York: Basic Books, 1976); and F. J. Sulloway,
Freud: Biologist of the Mind
(New York: Basic Books, 1979).

My colleagues and I also analyzed the mechanisms of classical conditioning. In 1983, Hawkins, Carew, and I delineated a presynaptic component, an enhancement of the mechanisms that contribute to sensitization. In 1992 Nicholas Dale and I found that the sensory neuron uses glutamate as its transmitter. In 1994, my former student David Glanzman and subsequently Robert Hawkins and I made the important observation that there is also an important postsynaptic component. See X. Y. Lin and D. L. Glanzman, “Long-term potentiation of
Aplysia
sensorimotor synapses in cell culture regulation by postsynaptic voltage,”
Biol. Sci
. 255 (1994): 113–18; and I. Antonov, I. Antonova, E. R. Kandel, and R. D. Hawkins, “Activity-dependent presynaptic facilitation and Hebbian LTP are both required and interact during classical conditioning in
Aplysia,” Neuron
37 (2003): 135–47.

For alternative views of the mechanisms of learning, see R. Adey, “Electrophysiological patterns and electrical impedance characteristics in orienting and discriminative behavior,”
Proc. Int. Physiol. Soc
. (Tokyo) 23 (1965): 324–29; quotation from p. 235; B. D. Burns,
The Mammalian Cerebral Cortex
(London: Arnold, 1958); quotation from p. 96; S. R. Cajal, “The Croonian Lecture. La Fine structure des centers nerveux,”
Proc. R. Soc. London Ser. B
55 (1894): 444–67; and D. O. Hebb,
The Organization of Behavior: A Neuropsychological Theory
(New York: John Wiley, 1949).

Other information for this chapter was drawn from the following:

Castellucci, V., H. Pinsker, I. Kupfermann, and E. R. Kandel. “Neuronal mechanisms of habituation and dishabituation of the gill-withdrawal reflex in
Aplysia.” Science
167 (1970): 1745–48. “The data indicate…” is from p. 1748.

Hawkins, R. D., T. W. Abrams, T. J. Carew, and E. R. Kandel. “A cellular mechanism of classical conditioning in
Aplysia
: Activity-dependent amplification of presynaptic facilitation.”
Science
219 (1983): 400–405.

Kandel, E. R.
A Cell-Biological Approach to Learning.
Grass Lecture Monograph I. Bethesda, Md.: Society for Neuroscience, 1978.

Kupfermann, I., V. Castellucci, H. Pinsker, and E. R. Kandel. “Neuronal correlates of habituation and dishabituation of the gill-withdrawal reflex in
Aplysia.” Science
167 (1970): 1743–45.

Pinsker, H., I. Kupfermann, V. Castellucci, and E. R. Kandel. “Habituation and dishabituation of the gill-withdrawal reflex in
Aplysia.” Science
167 (1970): 1740–43. “The analysis of the neural mechanisms…” is from p. 1740.

15: The Biological Basis of Individuality

The discussion of Helmholtz’s work on unconscious inference is based on C. Frith, “Disorders of cognition and existence of unconscious mental processes: An introduction,” in E. Kandel et al.,
Principles of Neural Science
, 5th ed. (New York: McGraw-Hill, forthcoming); R. M. Warren and R. P. Warren,
Helmholtz on Perception: Its Physiology and Development
(New York: John Wiley & Sons, 1968); R. J. Herrnstein and E. Boring, eds.,
A Source Book in the History of Psychology
(Cambridge, Mass.: Harvard University Press, 1965), especially pp. 189–93; and R. L. Gregory, ed.,
The Oxford Companion to the Mind
(Oxford: Oxford University Press, 1987), pp. 308–9.

For a discussion of Ebbinghaus, see H. Ebbinghaus,
Memory: A Contribution to Experimental Psychology
, trans. H. A. Ruger and C. E. Bussenius (New York: Teacher’s College/Columbia University, 1913); original German-language publication 1885.

For structural changes in
Aplysia
, see C. H. Bailey and M. Chen, “Long-term memory in
Aplysia
modulates the total number of varicosities of single identified sensory neurons,”
Proc. Natl. Acad. Sci. USA
85 (1988): 2373–77 and C. H. Bailey and M. Chen, “Time course of structural changes at identified sensory neuron synapses during long-term sensitization in
Aplysia,” J. Neurosci
. 9 (1989): 1774–80; C. H. Bailey and E. R. Kandel, “Structural changes accompanying memory storage,”
Annu. Rev. Physiol
. 55 (1993): 397–426.

Other information for this chapter was drawn from the following:

Cajal, S. R. “The Croonian Lecture: La fine structure des centres nerveux.”
Proc. R. Soc. London Ser. B 55
(1894): 444–67.

Dudai, Y.
Memory from A to Z.
Oxford: Oxford University Press, 2002.

Duncan, C. P. “The retroactive effect of electroshock on learning.”
J. Comp. Physiol. Psychol.
42 (1949): 32–44.

Ebert, T., C. Pantev, C. Wienbruch, B. Rockstroh, and E. Taub. “Increased cortical representation of the fingers of the left hand in string players.”
Science
270 (1995): 305–7.

Flexner, J. B., L. B. Flexner, and E. Stellar. “Memory in mice as affected by intracerebral puromycin.”
Science
141 (1963): 57–59.

Jenkins, W. M., M. M. Merzenich, M. T. Ochs, T. Allard, and E. Guic-Robles. “Functional reorganization of primary somatosensory cortex in adult owl monkeys after behaviorally controlled tactile stimulation.”
J. Neurophysiol.
63 (1990): 83–104.

16: Molecules and Short-Term Memory

For background of cyclic AMP, see R. J. DeLange, R. G. Kemp, W. D. Riley, R. A. Cooper, and E. G. Krebs. “Activation of skeletal muscle phosphorylase kinase by adenosine triphosphate and adenosine 3’, 5’-monophosphate.”
J. Biol. Chem.
243, no. 9 (1968): 2200–2208; E. G. Krebs, “Protein phosphorylation and cellular regulation, I” in
Les Prix Nobel (The Nobel Prizes)
, ed. Nobel Foundation (Stockholm: Almquist & Wiksell International, 1992); T. W. Rall and E. W. Sutherland, “The regulatory role of adenosine 3’, 5’-phosphate. Cold Spring Harbor Symp.,”
Quant. Biol.
26 (1961): 347–54; A. E. Gilman, “Nobel lecture. G Proteins and regulation of adenylyl cyclase,”
Biosci. Reports
15 (1995): 65–97; P. Greengard, “The neurobiology of dopamine signaling,” in
Les Prix Nobel (The Nobel Prizes)
, ed. Nobel Foundation, 262–81 (Stockholm: Almquist & Wiksell International, 2000).

For cAMP in
Aplysia
, see J. H. Schwartz, V. F. Castellucci, and E. R. Kandel, “Functioning of identified neurons and synapses in abdominal ganglion of
Aplysia
in absence of protein synthesis,”
J. Neurophysiol.
34 (1971): 939–53; H. Cedar, E. R. Kandel, and J. H. Schwartz, “Cyclic adenosine monophosphate in the nervous system of
Aplysia californica:
Increased synthesis in response to synaptic stimulation.”
J. Gen. Physiol.
60 (1972): 558–69; M. Brunelli, V. Castellucci, and E. R. Kandel, “Synaptic facilitation and behavioral sensitization in
Aplysia:
Possible role of serotonin and cyclic AMP.”
Science
194 (1976): 1178–81; also, V. F. Castellucci, E. R. Kandel, J. H. Schwartz, F. D. Wilson, A. C. Nairn, and P. Greengard. “Intracellular injection of the catalytic subunit of cyclic AMP-dependent protein kinase simulates facilitation of transmitter release underlying behavioral sensitization in
Aplysia.” Proc. Natl. Acad. Sci. USA
77 (1980): 7492–96.

For cAMP in
Drosophila
, see S. Benzer, “Behavioral mutants of
Drosophila
isolated by counter current distribution,”
Proc. Natl. Acad. Sci.
58 (1967): 1112–19; D. Byers, R. L. Davis, and J. R. Kiger, Jr., “Defect in cyclic AMP phosphodiesterase due to the dunce mutation of learning in
Drosophila melanogaster,” Nature
289 (1981): 79–81; Y. Dudai, Y. N. Jan, D. Byers, W. G. Quinn, and S. Benzer. “Dunce, a mutant of
Drosophila
deficient in learning.”
Proc. Natl. Acad. Sci. USA
73, no. 5 (1976): 1684–88.

Other information in this chapter was drawn from the following: