Eric Kandel

"Five separate pulses of serotonin, designed to simulate five shocks to the tail, strengthened the synaptic connection for days and led to the growth of new synaptic connections... that did involve the synthesis of new protein."

"Jacques Monod... published a paper entitled "Genetic Regulatory Mechanisms in the Synthesis of Protein." Using bacteria as a model system, they made the remarkable discovery that genes can be regulated—that is, they can be switched on and off like a water faucet."

"What is learning but a set of sensory signals from the environment, with different forms of learning resulting from different types or patterns of sensory signals?"

"Jacob and Monod found that in bacteria, genes are switched on and off by other genes. This led them to distinguish between effector genes and regulatory genes. Effector genes encode effector proteins... which mediate specific cellular functions. Regulatory genes encode proteins called regulatory proteins, which switch the effector genes on or off."

"Jacob and Monod not only outlined a theory of gene regulation, they also discovered the first regulators of gene transcription. These regulators come in two forms—repressors, genes that encode the regulatory proteins that shut genes off, and as later work showed, activators, genes that encode the regulatory proteins that turn genes on."

"In the Jacob-Monod model, signals from a cell's environment activate regulatory proteins that switch on the genes encoding particular proteins. This led [Philip] Goelet and me to wonder whether the crucial step in switching on long-term memory in sensitization might involve similar signals and similar gene regulatory proteins."

"Even though I had long been taught that the genes of the brain are the governors of behavior, the absolute masters of our fate, our work showed that, in the brain as in bacteria, genes are also servants of the environment. ...An environmental stimulus... activates modulatory interneurons that release serotonin. The serotonin acts on the sensory neuron to increase cyclic AMP and to cause protein kinase A and MAP kinase to move to the nucleus and activate CREB. The activation of CREB, in turn, leads to the expression of genes that changes the function and the structure of the cell."

"CREB's opposing regulatory actions provide a threshold for memory storage, presumably to ensure that only important, life-serving experiences are learned. Repeated shocks to the tail are a significant learning experience for an Aplysia, just as, say, practicing the piano or conjugating French verbs are to us: practice makes perfect, repetition is necessary for long-term memory. In principle, however, a highly emotional state... could bypass the normal restraints on long-term memory. In such a situation, enough MAP kinase molecules would be sent into the nucleus rapidly enough to inactivate all of the CREB-2 molecules, thereby making it easy for protein kinase A to activate CREB-1 and put the experience directly into long-term memory."

"Exceptionally good memory exhibited by some people may stem from genetic differences in CREB-2 that limit the activity of this repressor protein in relation to CREB-1."

"The same CREB switch is important for many forms of implicit memory in a variety of other species, from bees to mice to people."

"CPEB is the first self-propogating form of a prion known to serve a physiological function... perpetuation of synaptic facilitation and memory storage."

"The fact that a gene must be switched on to form a long-term memory shows clearly that genes are not simply determinants of behavior but are also responsive to environmental stimulation, such as learning."

"The growth and maintenance of new synaptic terminals makes memory persist. ...The ability to grow new synaptic connections as a result of experience appears to have been conserved throughout evolution. As an example... the cortical maps of the body surface are subject to constant modification in response to changing input from sensory pathways."

"Implicit memory is responsible not only for simple perceptual and motor skills but also, in principle, for the pirouettes of Margot Fonteyn, the trumpeting techniques of Wynton Marsalis, the accurate ground strokes of Andre Agassi, and the leg movements of an adolescent. Implicit memory guides us through well-established routines that are not consciously controlled."

"For all of us, explicit memory makes it possible to leap across space and time and conjure up events and emotional states that have vanished into the past yet somehow continue to live in our minds."

"Recall of memory is a creative process. What the brain stores is... only a core memory. Upon recall, this 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?"

"Mountcastle discovered that tactile sensation is made up of several distinct modalities; for example, touch includes... hard pressure on the skin as well as a light brush... He found that each distinct submodality has its own private pathway within the brain and that this segregation is maintained at each relay..."

"Cajal revealed the precision of the interconnections between populations of individual nerve cells. Mountcastle, Hubel, and Wiesel revealed the functional significance of those patterns of interconnections. They showed that the connections filter and transform sensory information on the way to and within the cortex, and that the cortex is organized into functional compartments, or modules."

"Each sensory system first analyzes and deconstructs, then restructures the raw, incoming information to its own built-in connections and rules—shades of Immanuel Kant."

"Aspects of visual perception—motion, depth, form, and color—are segregated from one another and conveyed in separate pathways in the brain, where they are brought together and coordinated into a unified perception."

"Segregation occurs in the primary visual area of the cortex, which gives rise to two parallel pathways. ...the "what" pathway, carries information about the form of an object... the "where" pathway, carries information about the movement of the object in space: where the object is located."

"The idea that different aspects of visual perception might be handled in separate areas of the brain was predicted by Freud at the end of the nineteenth century. ...a cortical defect that affected [the] ability to combine aspects of vision into a meaningful pattern. ...defects, which Freud called agnosias (loss of knowledge)..."

"What strategy does the brain use to read itself out? That question, which is central to the unitary nature of conscious experience, remains one of the many unresolved mysteries of the new science of mind."

"The firing of individual nerve cells involved in perceptual and motor processing is modified by attention and decision making."

"Birds in which spatial memory is particularly important—those that store food at a large number of sites, for example—have larger hippocampuses than other birds. ...London taxi drivers have a larger hippocampus than others the same age. ...the size of their hippocampus continues to increase with time on the job."

"Long-term potentiation helps stabalize the internal representation of space, and... attention, a defining feature of explicit memory storage, modulates the representation of space."

"O'Keefe... argued that many forms of explicit memory (for example, memory for people and objects) use spatial coordinates... we typically remember people and events in a spatial context."

"Because we do not have a sensory organ dedicated to space, the representation of space is a quintessentially cognitive sensibility: it is the binding problem writ large."

"For some representations of space the brain typically uses egocentric coordinates (centered on the receiver)... For other behaviors... the brain uses allocentric coordinates (centered on the world)."

"We did not realize that the hippocampus is concerned with perception of the environment and therefore represents multisensory experience..."

"Unlike vision, touch, or smell, which are prewired and based on Kantian a priori knowledge, the spatial map presents us with a new type of representation, one based on a combination of a priori knowledge and learning. The general capability for forming spatial maps is built into the mind, but the particular map is not. Unlike neurons in a sensory system, place cells are not switched on by sensory stimulation. Their collective activity represents the location where the animal thinks it is."

"By merely observing the electrical activity in the brain, Libet could predict what a person would do before the person was actually aware of having decided to do it. This finding caused philosophers of mind to ask: If the choice is determined in the brain before we decide to act, where is free will? ...choice in action, as in perception, may reflect the importance of unconscious inference. Libet proposes that... just before the action is initiated, consciousness is recruited to approve or veto the action."

"Die vielleicht letzte wissenschaftliche Grenze — die ultimative Herausforderung — besteht darin, die biologische Basis des Bewußtseins und der geistigen Vorgänge, durch die wir wahrnehmen, handeln, lernen und uns erinnern, zu verstehen."