In Search of Memory: The Emergence of a New Science of Mind
Citation (Chicago Style): Kandel, Eric R.. In Search of Memory: The Emergence of a New Science of Mind. W. W. Norton & Company, 2007. Kindle edition.
ONE
Bookmark – 2. A Childhood in Vienna > Page 12 · Location 348
Bookmark – 2. A Childhood in Vienna > Page 12 · Location 357
Bookmark – 2. A Childhood in Vienna > Page 18 · Location 416
Bookmark – 3. An American Education > Page 38 · Location 713
Bookmark – 3. An American Education > Page 40 · Location 732
TWO
Highlight(blue) – 4. One Cell at a Time > Page 67 · Location 1082
Parkinson’s disease attacks a certain class of interneurons;
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If and only if the sum of excitation exceeds that of inhibition by a critical minimum will the motor neuron signal the target muscle to contract.
Highlight(blue) – 5. The Nerve Cell Speaks > Page 88 · Location 1374
In this way a signal for a visual experience, a movement, a thought, or a memory is sent from one end of the neuron to the other. For their work, now
Highlight(blue) – 9. Searching for an Ideal System to Study Memory > Page 142 · Location 2125
the cellular mechanisms of learning and memory reside not in the special properties of the neuron itself, but in the connections it receives and makes with other cells in the neuronal circuit to which it belongs.
THREE
Highlight(blue) – 15. The Biological Basis of Individuality > Page 215 · Location 3163
Short-term memory produces a change in the function of the synapse, strengthening or weakening preexisting connections; long-term memory requires anatomical changes. Repeated sensitization training (practice) causes neurons to grow new terminals, giving rise to long-term memory, whereas habituation causes neurons to retract existing terminals. Thus, by producing profound structural changes, learning can make inactive synapses active or active synapses inactive.
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He then went on to show that when the concentration of dopamine is decreased in a rabbit, the animal develops symptoms that resemble Parkinson’s disease.
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Highlight(blue) – 17. Long-Term Memory > Page 240 · Location 3522
We had succeeded in tracing a simple learned response in Aplysia to the neurons and synapses that mediate it and had found that learning gives rise to short-term memory by producing transient changes in the strength of existing synaptic connections between sensory and motor neurons. Those short-term changes are mediated by proteins and other molecules already present at the synapse. We had discovered that cyclic AMP and protein kinase A enhance the release of glutamate from the terminals of the sensory neurons, and that this enhanced release is a key element in short-term memory formation. In brief, we had in Aplysia an experimental system whose molecular components we could manipulate experimentally in a logical way.
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we now know to be a fact: that even in a complex organism like a human being, almost every gene of the genome is present in every cell of the body. Every cell has in its nucleus all of the chromosomes of the organism and therefore all of the genes necessary to form the entire organism.
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Jacob and Monod proposed what ultimately proved to be the case—namely, that a liver cell is a liver cell, and a brain cell is a brain cell because in each cell type only some of those genes are turned on, or expressed; all of the other genes are shut off, or repressed. Thus, each cell type contains a unique mix of
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They postulated that every effector gene has in its DNA not only a coding region that encodes a particular protein but also a control region, a specific site now known as the promoter. Regulatory proteins bind to the promoter of effector sites and thereby determine whether the effector genes are going to be switched on or
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I now asked: What is the nature of the regulatory genes that respond to a specific form of learning, that is, to cues from the environment? And how do these regulatory genes switch a short-term synaptic change that is critical to a specific short-term memory into a long-term synaptic change that is critical to a specific long-term memory?
Highlight(blue) – 19. A Dialogue Between Genes and Synapses > Page 262 · Location 3834
In this paper, we proposed that if gene expression was required to convert short-term memory at a synapse into long-term memory, then the synapse stimulated by learning somehow had to send a signal to the nucleus telling it to turn on certain regulatory genes. In short-term memory, synapses use cyclic AMP and protein kinase A inside the cell to call for the release of more neurotransmitter.
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Conversely, a characteristic of age-related memory loss (benign senescent forgetfulness)
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insight into the computational power of the brain. It illustrates that even though a neuron may make one thousand or more synaptic connections with different target cells, the individual synapses can be modified independently, in long-term as well as short-term memory. The synapses’ independence of long-term action gives the neuron extraordinary computational flexibility.
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The second way in which prions differ from other proteins is that the dominant form is self-perpetuating;
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CPEB is the first self-propagating form of a prion known to serve a physiological function—in this case, perpetuation of synaptic facilitation and memory storage.
FOUR
Highlight(blue) – 20. A Return to Complex Memory > Page 281 · Location 4059
Recall of memory is a creative process. What the brain stores is thought to be only a core memory. Upon recall, this core memory is then elaborated upon and reconstructed, with subtractions, additions, elaborations, and distortions. What biological processes enable me to review my own history with such emotional vividness?
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heterosynaptically,
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homosynaptic
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neuromodulators are usually recruited to switch short-term homosynaptic plasticity into long-term heterosynaptic plasticity.
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Gary Lynch
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Almost every gene in the human genome exists in several different versions, called alleles, which are present in different members of the human population. Genetic studies of human neurological and psychiatric disorders had made it possible to identify alleles that account for behavioral differences in normal people as well as alleles that underlie many neurological disorders, such as amyotrophic lateral sclerosis, early onset Alzheimer’s disease, Parkinson’s disease,
Highlight(blue) – 22. The Brains Picture of the External World > Page 302 · Location 4368
Sensation is an abstraction, not a replication, of the real world.
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there is no single cortical area to which all other cortical areas report exclusively, either in the visual or in any other system. In sum, the cortex must be using a different strategy for generating the integrated visual image.
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already knew that attention was not simply a mysterious force in the brain but a modulatory process.
FIVE
Bookmark – 24. A Little Red Pill > Page 319 · Location 4586
Highlight(blue) – 24. A Little Red Pill > Page 327 · Location 4714
Half of the 60 percent have a slight memory impairment, sometimes called benign senescent forgetfulness, that progresses only slowly, if at all, with time and age. The remaining half, however (or 30 percent of the population over age seventy), develop Alzheimer’s disease, a progressive degeneration of the brain.
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mouse has a defect in spatial memory, it implies that something is wrong with the hippocampus.
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These results support the notion that the decline in hippocampus-dependent learning in older animals is due, at least in part, to an age-related deficit in the late phase of long-term potentiation. Perhaps more important, they suggest that benign senescent forgetfulness may be reversible.
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Parkinson’s disease is a disorder of the substantia nigra,
Highlight(blue) – 25. Mice, Men, and Mental Illness > Page 339 · Location 4886
Thus, not only do animals experience fear, but we can tell when they are anxious. We can, so to speak, read their thoughts. This insight was first set out by Charles Darwin in his classic 1872 study The Expression of the Emotions in Man and Animals.
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wrote: “We feel sorry because we cry, angry because we strike, afraid because we tremble, and not that we cry, strike or tremble because we are sorry, angry or fearful, as the case may be.”
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after a single exposure to a threat, the amygdala can retain the memory of that threat throughout an organism’s entire life. How does this come about?
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pyramidal cells
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whom I would later share the Nobel Prize, made three remarkable discoveries that provided critical insights into both Parkinson’s disease and schizophrenia. First, he discovered dopamine and showed it to be a neurotransmitter in the brain. Next, he found that when he lowered the concentration of dopamine in the brain of experimental animals by a critical amount, he produced a model of Parkinson’s disease. From this finding he argued that parkinsonism may result from a lowered concentration of dopamine in regions of the brain that are involved in motor control. He and others tested this idea and found that they could reverse the symptoms of Parkinson’s disease by giving patients additional dopamine.
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abnormally large number of D2 receptors in the striatum, an area of the brain that, as we have seen, is usually involved in feeling good. Having an unusually large number of D2 receptors available to bind dopamine results in increased dopamine transmission. Simpson, Kellendonk,
Highlight(blue) – 27. Biology and the Renaissance of Psychoanalytic Thought > Page 370 · Location 5334
In fact, if psychotherapeutic changes are maintained over time, it is reasonable to conclude that different forms of psychotherapy lead to different structural changes in the brain, just as other forms of learning do.
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the basal ganglia, the caudate nucleus, is the primary recipient of information coming from the cerebral cortex and other regions of the brain.
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“But, ineffably,” she writes, “psychotherapy heals. It makes some sense of the confusion, reins in the terrifying thoughts and feelings, returns some control and hope and possibility of learning from it all. Pills cannot, do not, ease one back into reality.”
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As a result, most students of the brain believe, as Freud did, that we are not conscious of most cognitive processes, only of the end result of those processes. A similar principle seems to apply to our conscious sense of free will.
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Nagel argues that our complete lack of insight into the elements of subjective experience should not prevent us from discovering the neural correlates of consciousness and the rules that relate conscious phenomena to cellular processes in the brain.
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than 100,000 human expressions, was able to show, as did Charles Darwin before him, that irrespective of sex or culture, conscious perceptions of seven facial expressions—happiness, fear, disgust, contempt, anger, surprise, and sadness—have virtually the same meaning to everyone
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“our conscious mind may not have free will, but it does have free won’t.”
SIX
Highlight(blue) – 29. Rediscovering Vienna via Stockholm > Page 405 · Location 5820
For a decade before Austria joined with Germany, a significant fraction of the Austrian population belonged to the Nazi party. Following annexation, Austrians made up about 8 percent of the population of the greater German Reich, yet they accounted for more than 30 percent of the officials working to eliminate the Jews. Austrians commanded four Polish death camps and held other leadership positions in the Reich: in addition to Hitler, Ernst Kaltenbrunner, who was head of the Gestapo, and Adolf Eichmann, who was in charge of the extermination program, were Austrians. It is estimated that of the 6 million Jews who perished during the Holocaust, approximately half were killed by Austrian functionaries led by Eichmann.
Highlight(blue) – 30. Learning from Memory: Prospects > Page 423 · Location 6084
What neural circuits are important for various types of memory? How are internal representations
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of a face, a scene, a melody, or an experience encoded in the brain?
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First, I would like to understand how the unconscious processing of sensory information occurs and how conscious attention guides the mechanisms in the brain that stabilize memory.
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From this perspective, to which most neural scientists now subscribe, most of our mental life is unconscious; it becomes conscious only as words and images. Brain imaging could be used to connect psychoanalysis to brain anatomy and to neural function by determining how these unconscious processes are altered in disease states and how they might be reconfigured by psychotherapy.
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Cori Bargmann, a geneticist now at Rockefeller University, has studied two variants of C. elegans that differ in their feeding patterns. One variant is solitary and seeks its food alone. The other is social and forages in groups. The only difference between the two is one amino acid in an otherwise shared receptor protein. Transferring the receptor from a social worm to a solitary worm makes the solitary worm social.
Glossary
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