Table Of ContentKarl Peter Giese · Kasia Radwanska
Editors
Novel
Mechanisms
of Memory
Novel Mechanisms of Memory
Karl Peter Giese • Kasia Radwanska
Editors
Novel Mechanisms
of Memory
Editors
Karl Peter Giese Kasia Radwanska
Institute of Psychiatry Nencki Institute of Experimental Biology
King’s College London Polish Academy of Sciences
London , UK Warsaw , Poland
ISBN 978-3-319-24362-7 ISBN 978-3-319-24364-1 (eBook)
DOI 10.1007/978-3-319-24364-1
Library of Congress Control Number: 2015956778
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Introd uction
U nderstanding the mechanisms of memory is one of the biggest challenges of sci-
ence. In order to face this challenge, new technologies are being intensively devel-
oped. Molecular biology tools, high-resolution microscopy, and optogenetics today
allow for the precise analysis of signal transduction cascades within the living ani-
mal, cell, or single dendritic spine. Transgenic animals with very sophisticated gene
manipulations and more accurate animal models of mental disorders are used to
decipher the molecular basis of cognition. But still we do not know the answers to
the very simple question: how and where is long-term memory stored? These basic
gaps in our knowledge drive us to ask more and more detailed and precise questions
about the molecular and cellular basis of cognition.
The main progress in the learning and memory fi eld has been made with the
investigation of simple animal models, such as Pavlovian fear conditioning studies
with mice. During such training, an animal is exposed to a neutral conditioned stim-
ulus (CS) (a new context, sound, or light signal) and an aversive unconditional stim-
ulus (US) (e.g., electric shock). As a result of such experience, the conditioned
stimulus acquires secondary aversive properties. The intensity of freezing response
of the animal after the reexposure to the conditioned stimulus is used as a measure
of fear memory strength. The early studies indicated several factors which prevent
fear memory formation, and these included inhibitors of protein synthesis and tran-
scription, antagonists of glutamatergic receptors, as well as inhibitors of intracellu-
lar cascades such as extracellular signal-regulated kinases 1 and 2 (ERK 1 and 2),
α-isoform of calcium-/calmodulin-dependent kinase II (αCaMKII), or protein
kinase A (PKA). These observations defi ned the basic molecular processes underly-
ing memory formation and indicated directions of the research in the fi eld. Thus
recently, the model has been extensively developed. In the current book, we gath-
ered some of the novel achievements of the fi eld of the molecular basis of memory.
These include ideas which span from the remodelling of the extracellular matrix,
dynamic changes of the morphology and function of dendritic spines to epigenetic
modifi cations occurring in the cell nucleus (Fig. 1) . In nine chapters, new and
important ideas related to learning and memory processes will be presented. In
Chap. 1 , the idea that memory after consolidation still can be dynamically r emodelled
v
vi Introduction
CREB Inverse synaptic 6
tagging
Epigenetics and
memory 8 7 CREB in memory
CaMKII
Arc P A
aCaMKII
T286
Dynamic nature of
1 memory 5 Multiininn emrveamteodr yspines
AMPAR endocytosis in
2
memory
CaMKII
CaMKII regulates
spine structure 3
MMP-9 in learning MMP-9 and plasticity aCaMKII
9 NMDAR autophosphorylation
CaMKII 4 in memory
T286
P
AMPAR
Fig. 1 Novel mechanisms of memory drawn by Gosia Borczyk
will be introduced. This process involves the transport of AMPA receptors (Chap.
2 ). Furthermore, the role of CaMKII as a controller of synaptic function and infor-
mation storage, which plays both enzymatic and structural roles, will be discussed
(Chap. 3 ) together with the presentation of data supporting the critical role of alpha-
CaMKII-T286 autophosphorylation in learning and memory (Chap. 4 ) . The novel
mechanism for memory formation involving the formation of big multi-i nnervated
dendritic spines will be proposed in Chap. 5 . We will also introduce the idea of the
inverse synaptic tagging by Arc, the process which is suggested as a mechanism for
the control of dendritic spine strength via the regulation of AMPA receptor surface
expression by endocytosis (Chap. 6 ). Next, the possible role of CREB transcription
factor as a universal memory enhancer in fl ies and mice (Chap. 7 ) and the function
of chromatin modifi cations and DNA methylation in several forms of mammalian
memory and associated synaptic plasticity (Chap. 8 ) will be critically discussed.
Finally, a possible mechanistic role of an extracellular matrix metalloproteinase,
MMP-9, in synaptic plasticity at the level of structural modulation of spine mor-
phology will be proposed (Chap. 9 ).
Introduction vii
W e are aware of the fact that the topics covered in the book are just the tip of the
iceberg of memory, but we believe that they are at the same time a great step toward
understanding the complexity of the brain and the processes it governs. Therefore,
we would like to express our gratitude for all contributing authors who were willing
to share with us their exciting discoveries and ideas.
London, UK Karl Peter Giese
Warsaw, Poland Kasia Radwanska
About the Editors
Karl Peter Giese s tudied biochemistry at the Ruhr University in Bochum,
Germany, and earned a Ph.D. in neuroscience at the ETH Zurich in Switzerland. As
a postdoctoral fellow at Cold Spring Harbor Laboratory, in the New York, USA, he
began to investigate molecular and cellular mechanisms of memory. From 1998
until 2006, he worked as lecturer and reader at University College London, UK, and
since 2006, he is Professor of Neurobiology of Mental Health at King’s College
London, UK. He has published more than 80 papers, and his H-index is currently 42.
Kasia Radwanska s tudied evolutionary ecology of freshwater snails at Warsaw
University, Poland, and Bangor University, Wales. She earned her Ph.D. in neuro-
science at Nencki Institute of Experimental Biology in Warsaw, where she began
studies on the molecular basis of addiction. Next, she continued as a Marie Curie
postdoctoral fellow at King’s College London, UK in Prof. Karl Peter Giese’s group
studying molecular and cellular mechanisms of memory. Since 2013, she is a group
leader at Nencki Institute of Experimental Biology working on molecular basis of
alcohol addiction and memory.
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