Book Review: In Search of Memory: the emergence of a new science of the mind.

Book Review: In Search of Memory: the emergence of a new science of the mind.
Eric R. Kandel. W. W. Norton, 2006.

After a semester of exploring the workings of the brain and the mind, what (and how) will you remember? In his book In search of memory: the emergence of the mind, Eric Kandel—2000 Nobel Prize winner in Physiology or Medicine for his work on signal transduction in the nervous system—presents a personal account of his lifelong attempt to understand the biological basis for memory set against a background of the development of modern cognitive neuroscience and the evolution of a new scientific paradigm. Kandel touches upon practically all of the topics explored this semester: the structure and function of neurons, how cells communicate via action potentials and neurotransmitter, the dynamic nature and multi-routed nature neuronal systems that incorporate both excitatory and inhibitory signals, how synaptic signals are strengthened. He also explores in greater detail the nature of short-term and long-term memory and the role that genes play with much more beside. Reminiscent of Watson’s Double Helix, In Search of Memory conveys a passion and excitement for scientific discovery; but where Watson’s 1968 work reflected his youthfulness, Kandel’s work demonstrates his sensitivity and maturity. Kandel’s familiarity with the key players and important contributions to his field of scientists and post-doctoral students is inspiring. We are presented with an almost Kuhninan intellectual account of the structure of the scientist revolution/evolution of neuroscience. We see how new ideas arise out of a mosaic of existing beliefs. Indeed, after reading Kandel’s five hundred page book, one gets the sense of seeing not merely the forest of memory and neurons, but also of the trees proteins and genes that play a role in the strengthening of synaptic connections.

Although there are many themes explored in Kandel’s work, two are particularly relevant and important in relationship to this course: first, the historical and evolutionary trends in attempts to understand the mind and how it operates; and second, an elucidation of the how memory (both short and long) is formed and stored in the brain. Understanding historical and evolutionary trends are crucial to appreciating the advantages of current methods and approaching in a given scientific field. When asking questions about the nature of the mind, it is critical to understand what questions have already been asked in order to appreciate the new questioned that can be asked. Kandel is useful here, describing four phases in the scientific approach to the study of the mind in the modern age.

In the first phase we follow Luigi Galvani’s excitement in 1791 at discovering that nerve and muscle cells are capable of conducting and generating electrical current to the ‘father of modern neuroanatomy’, Santiago Ramón y Cajal, a contemporary of Freud’s, who helped to elucidate several important principles in the theory of neural organization known as the neuron doctrine: namely, that the neuron is the fundamental structural unit and is the fundamental unit responsible for signaling of the brain; that there is a small gap called the synapse at the endpoints or terminals of one neuron and the beginning of the next neuron; that the connections made between adjacent neurons are like circuits and signals traveling along these routes in predictable patterns which includes sensory, motor and inter-neurons; and finally, that the signals conveyed have directionality, with flow of signals typically occurring in the same direction. Cajal’s contemporary Charles Sherrington would clarify that cells could have either an excitatory or inhibitory effect on cells.

In the second phase (1920s), Edgar Douglas Adrian was able to uncover the nature of the all-or-none actional potential across the nervous system to convey messages. He also established that the intensity of a stimulus is directly related to the frequency of action potentials emitted. The third phase focuses on the work of Julius Bernstein at the beginning of the twentieth century who investigated the mechanisms that underlie the action potential and the nature of the membrane. He concluded that the cell membrane was a barrier to all the ions in the cell except potassium, but that ions were able to enter and leave the cell via specialized ion channels. This arrangement allowed for the establishment of a resting membrane potential. The fourth phase centered on the development of the ionic hypotheses and the work of Andrew Huxley. By studying the axon, he demonstrated that an action potential is caused by the selective permeability of the membrane to specific ions.

Yet it was the work of psychologists and psychoanalysts that inspired Kandel’s interest. Kandel was initially attracted to psychoanalysis because it focused on those “aspects of behavior that could be publicly observed and objectively quantified”, rather than the introspective and philosophical approaches that predominated attempts to understand the mind before the twentieth century. He originally planned to become a physician in order to train as a psychiatrist practicing psychoanalysis. His future wife, Denise, whom he met while in medical school in 1955, was a Bryn Mawr College graduate and Ph.D. candidate in medical sociology at Columbia University. She encouraged him to pursue his research interests in understanding the biological basis from memory. The evolution of Kandel’s questions about the nature of memory is fascinating. While a medical student during research with researcher Harry Grundfest in Columbia, he shifted attention away from isolating a biological basis for Freud’s structural theory of the mind to focusing on how the nerve cell functions. Working with Grundfest forces him to appreciate that electrical signaling of neurons represents the language of the mind and that a reductionistic approach were the key to understanding the nature of the mind.

Years later, Kandel would use these two ideas of reductionism and cell function to study the the nature of memory and behavior in the giant marine snail Aplysia. Though initially criticized and ignored by others working in the field of neurophysiology, Kandel stuck to the study the creature because it had a comparatively small number of cells (200,000 compared to the 100 billion in the mammalian brain) grouped in nine main ganglia that were many times larger than those in mammals, allowing for the easier mapping of neuronal circuitry. By mapping out neuronal circuitry Kandel was able to develop analogs of learning in the creature to improve understanding of the function of humans and link actual changes in the synapse to instances of learning and memory. He was able to establish with fellow researchers the “neuronal controls of a behavioral response mediated by the abdominal ganglion in Aplysia”. Sensitization and habituation could alter the strength of synaptic connection in different ways; sensitization and classical conditioning strengthens and increases the number synaptical connections, while habituation weakens and decreases the number of synpatical connections. Thus he was able to discover the nature behind the key elements of (what we have termed in this course as) the central pattern generator which is strengthened established by experience.

Eventually, Kandel help to demonstrate how short-term memory involves temporary strengthening of pre-existing synaptic linkages and the modification of the neuron. Long-term memory differed from short-term memory in that it involved in the altering of genes as well as protein synthesis, followed by the development and growth of synaptic association in already existing circuits. Long-term memory is facilitated cAMP (cyclic adenonsine monophosphate) by signaling pathways by in the neuron. This chemical helps to initiate a series of chemical processes in the cell that help convert a transient stimulus into a more persistent change. In long-term memory, as a result of prior stimulus a sensory cell’s nucleus send dormant messenger RNA to axon terminals. These cause pulses of serotonin, a neurotransmitter, at one terminal to convert a prion-like protein called CPEB which is present at all synapses into a more dominant and self-perpetuating form. This new dominant CPEB can then activate dormant messenger RNA which can in turn activate protein synethesis at a new synaptic terminal. This phenomemon helps to stabilize the synaptic connection and maintain memory. It was for his elucidation of this process that Kandel was awarded the 2000 Nobel Prize winner in Physiology or Medicine.

Ultimately, for me In search of memory serves as a potent reminder of why I have felt compelled from a strong interest in social sciences to the biological sciences general. He demonstrates that science benefits from creativity and unconventional thinking. There is optimism about medicine and research which he could not elsewhere. He is a firm believer that “it is important to be bold, to tackle difficult problems, especially those that appear initially to be messy and unstructured” and that “one should not be afraid to try new things”. I am certain therefore that Eric Kandel would approve of the nature and structure of this course. Our classmates, like Kandel, have done an excellent job of trying to blend the art, science and history of the new neuroscience; yet we, like Kandel, will undoubtedly lose some readers. Some portions of In Search of Memory will have just a tad too much scientific details for some. Similarly, his extensive review of history—both personal and of the scientific field—will undoubtedly cause some ‘true scientists’ to skim certain pages. Yet the book, like this course, is not at a disadvantage for this because both provide a wide audience both the ability and flexibility to learn about the mind which is a most noble goal.