The formation of lasting, long-term memory occurs gradually, over time, following learning. A century ago Mueller and Pilzecker (1900) proposed that the neural processes underlying new memories persist in a short-lasting modifiable state and then, with time, become consolidated into a relatively long-lasting state. Later, hebb (1949) proposed that the first stage of the "dual-trace" memory system is based on reverberating neural circuits and that such neural activity induces lasting changes in synaptic connections that provide the basis for long-term memory.
Clinical and experimental evidence strongly supports the hypothesis that memory storage is time-dependent. Disruption of brain activity shortly after learning impairs long-term memory. In humans, acute brain trauma produces retrograde amnesia, a selective loss of memory for recent experiences (Burnham 1903; Russell and Nathan 1946) and in animals retrograde amnesia is induced by many treatments that impair brain functioning, including electrical brain stimulation and drugs (McGaugh and Herz 1972). Additionally, and more importantly, in humans as well as animals (Soetens et al. 1995), stimulant drugs administered shortly after learning enhance memory. Drugs affecting many neurotransmitter and hormonal systems improve long-term memory when they are administered within a few minutes or hours after training (McGaugh 1973, 1983). Extensive evidence indicates that the drugs enhance the consolidation of long-term memory.
Our memories of experiences vary greatly in strength. Some memories fade quickly and completely, whereas others last a lifetime. Generally, remembrance of experiences varies with their significance; emotionally arousing events are better remembered (Christianson 1992). William james observed that, "An experience may be so exciting emotionally as almost to leave a scar on the cerebral tissue" (James 1890). Studies of retrograde amnesia and memory enhancement provide important clues to the physiological systems underlying variations in memory strength. In particular, the finding that drugs enhance memory consolidation suggests that hormonal systems activated by emotional arousal may influence consolidation (Cahill and McGaugh 1996).
Emotionally exciting experiences induce the release of adrenal hormones, including the adrenal medullary hormone epinephrine (Adrenaline) and the adrenal cortex hormone corticosterone (in humans, cortisol). Experiments with animal and human subjects indicate that these hormones, as well as other hormones released by learning experiences, play an important role in regulating memory storage (Izquierdo and Diaz 1983; McGaugh and Gold 1989). Administration of epinephrine to rats or mice shortly after training enhances their long-term memory of the training (Gold, McCarty, and Sternberg 1982). b-adrenergic antagonists such as propranolol block the memory enhancement induced by epinephrine. Comparable findings have been obtained in studies with human subjects. The finding that b-adrenergic antagonists block the enhancing effects of emotional arousal on long-term memory formation in humans supports the hypothesis that b-adrenergic agonists, including epinephrine, modulate memory storage (Cahill et al. 1994). Additionally, studies of the effects of corticoster-one, as well as synthetic glucocorticoid receptor agonists and antagonists, indicate that memory storage is enhanced by glucocorticoid agonists and impaired by antagonists. Furthermore, hormones of the adrenal medulla and adrenal cortex interact in modulating memory storage: metyrapone, a drug that impairs the synthesis and release of corticoster-one, blocks the effects of epinephrine on memory consolidation (Sandi and Rose 1994; De Kloet 1991; Roozendaal, Cahill, and McGaugh 1996).
Recent research has revealed brain regions mediating drug and hormone influences on memory storage. Considerable evidence indicates that many drugs and hormones modulate memory through influences involving the amygdaloid complex. It is well established that electrical stimulation of the amygdala modulates memory storage and that the effect is influenced by adrenal hormones (Liang, Bennett, and McGaugh 1985). Lesions of the stria terminalis (a major amygdala pathway that connects the amygdala with many brain regions) block the memory-modulating effects of many drugs and hormones, including those of adrenal hormones. Furthermore, lesions of the amygdala and, more specifically, lesions of the basolateral amygdala nucleus, also block the effects of adrenal hormones on memory storage (McGaugh, Cahill, and Roozendaal 1996).
In humans, amygdala lesions block the effects of emotional arousal on long-term memory (Cahill et al. 1995). In animals, infusions of b-adrenergic and glucocorticoid antagonists into the amygdala impair memory, whereas infusions of b-adrenergic agonists (e.g., norepinephrine) and glucocorticoid receptor agonists into the amygdala after training enhance memory. As was found with lesions, the critical site for infusions is the basolateral amygdala nucleus (Gallagher et al. 1981; Liang, Juler, and McGaugh 1986; McGaugh et al. 1996). Findings such as these indicate that the basolateral amygdala nucleus is an important and perhaps critical brain region mediating arousal-induced neuro-modulatory influences on memory storage.
Thus, there is extensive evidence from human and animal studies that the amygdala is critically involved in modulating memory consolidation. However, it is also clear from the findings of many studies that the amygdala is not the neural locus of long-term memory. Lesions of the amygdala induced after training do not block retention of the memory of the training (Parent, West, and McGaugh 1994). Additionally, the amygdala is not the locus of neural changes underlying the enhanced memory induced by infusing drugs into the amygdala immediately after training. Drug infusions administered into the amygdala post training enhance long-term memory for training in many types of tasks, including tasks known to involve the hippocampus or caudate nucleus. Furthermore, inactivation of the amygdala with lidocaine infusions prior to retention testing does not block the enhanced memory (Packard, Cahill, and McGaugh 1994).
Research with humans has provided additional evidence that amygdala activation is involved in modulating the consolidation of long-term memory. In subjects tested several weeks after viewing emotionally arousing film clips, memory of the content of the film clips correlated very highly with activation of the amygdala when viewing the film clips, as indicated by positron emission tomography (PET) brain scans (Cahill et al. 1996).
The formation of new long-term memory must, of course, involve the formation of lasting neural changes. Additionally, the strength of the induced neural changes, as subsequently reflected in long-term memory, is modulated by the actions of specific hormonal and brain systems activated by learning experiences. Such modulation serves to ensure that the significance of experiences will influence their remembrance. Investigations of the processes and systems underlying the modulation of memory storage are providing new insights into how memories are created and sustained.
—James L. McGaugh References
Burnham, W. H. (1903). Retrograde amnesia: Illustrative cases and a tentative explanation. Am. J. Psychol. 14: 382-396. Cahill, L., and J. L. McGaugh. (1996). Modulation of memory storage. Current Opinion in Neurobiology 6: 237-242. Cahill, L., B. Prins, M. Weber, and J. L. McGaugh. (1994). 0-Adrenergic activation and memory for emotional events. Nature 371: 702-704. Cahill, L., R. Babinsky, H. J. Markowitsch, and J. L. McGaugh. (1995). The amygdala and emotional memory. Nature 377: 295-296.
Cahill, L., R. J. Haier, J. Fallon, M. Alkire, C. Tang, D. Keator, J. Wu, and J. L. McGaugh. (1996). Proc. Natl. Acad. Sci. U.S.A. 93: 8016-8021.
Christianson, S. -A., Ed. (1992). Handbook of Emotion and Memory: Current Research and Theory. Hillsdale, NJ: Erlbaum. De Kloet, E. R. (1991). Brain corticosteriod receptor balance and homeostatic control. Neuroendocrinology 12: 95-164. Gallagher, M., B. S. Kapp, J. P. Pascoe, and P. R. Rapp. (1981). A neuropharmacology of amygdaloid systems which contribute to learning and memory. In Y Ben-Ari, Ed., The Amygdaloid Complex. Amsterdam: Elsevier. Gold, P. E., R. McCarty, and D. B. Sternberg. (1982). Peripheral catecholamines and memory modulation. In C. Ajmone Marson and H. Matthies, Eds., Neuronal Plasticity and Memory Formation. New York: Raven Press, pp. 327-338. Hebb, D. O. (1949). The Organization of Behavior. New York: Wiley.
Izquierdo, I., and R. D. Diaz. (1983). Effect of ACTH, epineph-rine, b-endorphin, naloxone and of the combination of nalox-one or b-endorphin with ACTH or epinephrine on memory consolidation. Psychoneuroendocrinology 8: 81-87. James, W. (1890). The Principles of Psychology. New York: Henry Holt.
Liang, K. C., C. Bennett, and J. L. McGaugh. (1985). Peripheral epinephrine modulates the effects of posttraining amygdala stimulation on memory. Behav. Brain Res. 15: 83-91. Liang, K. C., R. G. Juler, and J. L. McGaugh. (1986). Modulating effects of posttraining epinephrine on memory: involvement of the amygdala noradrenergic system. Brain Research 368: 125133.
McGaugh, J. L. (1973). Drug facilitation of learning and memory.
Ann. Rev Pharmacol. 13: 229-241. McGaugh, J. L. (1983). Hormonal influences on memory. Ann. Rev. Psychol. 34: 297-323.
McGaugh, J. L., and P. E. Gold. (1989). Hormonal modulation of memory. In R. B. Rush and S. Levine, Eds., Psychoendocrinol-ogy. New York: Academic Press.
McGaugh, J. L., and M. J. Herz. (1972). Memory Consolidation. San Francisco: Albion.
McGaugh, J. L., L. Cahill, and B. Roozendaal. (1996). Involvement of the amygdala in memory storage: Interaction with other brain systems. Proc. Natl. Acad. Sci. U.S.A. 93: 1350813514.
Mueller, G. E., and A. Pilzecker. (1900). Experimentelle Beiträge zur Lehre vom Gedächtnis. Z. Psychol. 1: 1-288.
Packard, M. G., L. Cahill, and J. L. McGaugh. (1994). Amygdala modulation of hippocampal-dependent and caudate nucleus-dependent memory processes. Proc. Natl. Acad. Sci. U.S.A. 91: 8477-8481.
Parent, M. B., M. West, and J. L. McGaugh. (1994). Memory of rats with amygdala lesions induced 30 days after footshock-motivated escape training reflects degree of original training. Behavioral Neuroscience 6: 1959-1064.
Roozendaal, B., L. Cahill, and J. L. McGaugh. (1996). Interaction of emotionally activated neuromodulatory systems in regulating memory storage. In K. Ishikawa, J. L. McGaugh, and H. Sakata, Eds., Brain Processes and Memory, Excerpta Medica International Congress Series 1108. Amsterdam: Elsevier, pp. 39-54.
Russell, W. R., and P. W. Nathan. (1946). Traumatic amnesia. Brain 69: 280-300.
Sandi, C., and S. P. R. Rose. (1994). Corticosterone enhances long-term retention in one-day old chicks trained in a weak passive avoidance paradigm. Brain Research 647: 106-112.
Soetens, E., S. Casear, R. D'Hooge, and J. E. Hueting. (1995). Effect of amphetamine on long-term retention of verbal material. Psychopharmacology 119: 155-162.
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Have you ever been envious of people who seem to have no end of clever ideas, who are able to think quickly in any situation, or who seem to have flawless memories? Could it be that they're just born smarter or quicker than the rest of us? Or are there some secrets that they might know that we don't?