book review© 2008 Nature Publishing Group http://www.nature.com/natureneuroscience

From eIF2alpha to Ebbinghaus
The Neurobiology ofLearning and Memory
by Jerry W Rudy
Sinauer Associates, 2008
380 pp, hardcover, $74.95
ISBN 0878936696

Reviewed by Paul W Frankland &Karim Nader
Many of the concepts and methodologies that dominate ­contemporary
studies of learning and memory were developed around the turn of thetwentieth century. It was in this ‘golden age’ that German ­psychologist
Hermann Ebbinghaus developed the first empirical approaches for­studying human memory, and, around the same time, the Russian­physiologist Ivan Pavlov and the American ­psychologist Edward
Thorndike developed the behavioral ­frameworks for ­studying these­processes in ­nonhuman experimental subjects. In bringing ­scientificrigor to the study of learning and memory, Ebbinghaus, Thorndike,
Pavlov and others ­provided the impetus for twentieth and twenty-firstcentury ­scientists to begin to look inside the ‘black box’ of learning andmemory and to ultimately develop ­neurobiological accounts of theseprocesses. In his new book, The Neurobiology of Learning and Memory,
Jerry Rudy takes us on a journey from the work of these ­pioneers tocontemporary ­neurobiological studies where, armed with a plethoraof imaging and molecular tools, today’s ­neurobiologists are getting­unprecedented views inside of this black box. The challenge for this book,and for the field in general, is to bring together such diverse ­observations
into coherent models of how experience modifies the brain.
In taking this journey, Rudy chooses to start at the bottom and work
his way up. Accordingly, the chapters are organized around three major
themes: the synaptic basis of memory, memories and ­molecules, andneural systems and memories. He begins with ­synaptic plasticity, ablydescribing how experience alters existing synaptic connections via­long-term potentiation– or long-term depression–type ­mechanisms.
The emphasis here is on the molecular ­machinery underlying thesechanges and includes detailed discussion of ­post-translational­modification of existing synaptic proteins, receptor trafficking andthe transcriptional mechanisms underlying the stabilization of­synaptic changes. Although this first section describes experiments
using reduced preparations (such as brain slices), the focus shifts inthe second part of the book to the whole animal. Here Rudy ­evaluates

Paul Frankland is in the Program in Neurosciences and Mental Health at
The Hospital for Sick Children, 555 University Avenue, Toronto, ON,
M5G 1X8, Canada. Karim Nader is at the Department of Psychology,
McGill University, 1205 Dr. Penfield, Montreal, QC, H2A1B1, Canada.
e-mail: karim.nader@mcgill.canature neuroscience volume 11 | number 12 | DECEMBER 2008

whether the molecular machinery required for ­synaptic plasticity
is also required for behavioral plasticity or ­learning and memory.
Picking up on parallel themes in the first ­section, we ­follow the welltrodden path from NMDA and AMPA ­receptors through CaMKII to a
final destination of CREB, the putative gateway to long-term memory.
In the third section, Rudy turns his attention to the ­different ­neuralsystems that support memory, with a particular ­emphasis on the­hippocampus. This is Rudy’s bedrock and he expertly guides ­readers
through different theories of hippocampal function.
In many textbooks, scientific progress is presented as a staid, ­logicalprocess, inevitably converging on some set of scientific truths orfacts. As many of us are quick to recognize, progress is more ­typically­characterized by an unremitting series of claims and counter-claims,
with ­unexpected observations leading to paradigmatic shifts. It is shaped
not only by data but also by fashions, ­personalities and the ­ensuing,often emotionally laden, debates between rival ­factions. The studyof learning and memory is no exception and, ­straying from ­standard­textbook convention, Rudy highlights ­current areas of ­controversy anddebate. He casts his most ­critical eye over debates to which he himself
has contributed, ­questioning, for ­example, the ­specificity of widely usedtranslational inhibitors such as ­anisomycin, the generality of graded­retrograde amnesia following hippocampal damage and ­emphasizing
the difficulties in interpreting behavioral data from conventional
knockout mice. Although some may quibble with Rudy’s presentation(and occasional attempted resolution) of some of these debates, it isnonetheless a refreshingly nuanced view of the ­current state of affairs.
This dynamic view of the scientific process is ­further brought to life bypictures of many of the main ­protagonists throughout the book. From
Tulving to Tonegawa and Squire to Svoboda, the reader is treated tomug shots of the famous and ­influential.
Given the current diversity of approaches, it is undoubtedly a ­daunting
task to bring together contemporary studies of the ­neurobiology of­learning and memory into a single tome. Rudy ­readily acknowledges thathe covers this expansive field with ­relatively broad brushstrokes, hesitant
to become bogged down in technical detail. The advantage of this ­strategy
is that it makes the material ­readily accessible for both ­undergraduateand graduate-level students. Unavoidably, however, there are some­notable omissions. Most ­notably, the book is nearly ­exclusively focusedon rodent studies. Although we ­unquestionably ­benefit from Rudy’s
extensive knowledge of this ­literature, this ­narrows the focus somewhat(especially at the expense of more molecular ­analyses in flies, sea slugs
and worms). Furthermore, ­several very active subfields in ­learning andmemory are conspicuous in their absence. For example, when ­outlining
the types of ­computations ­carried out by medial ­temporal lobe ­structures
such as the ­hippocampus and ­entorhinal cortex, there is surprisingly
no ­discussion of place cells or grid cells. Likewise, ­aficionados of adultneurogenesis might be ­disappointed that this major form of structural
plasticity is not ­discussed in the book.
These omissions aside, there is still more than enough here forstudents of learning and memory. The real strength of this book isin placing contemporary, molecular-centric studies of learning andmemory in a broader historical context, that is, tracing a path fromeIF2alpha to Ebbinghaus.
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