Current
Behavioral Plasticity: From
Learning to Addiction
Executive Editor: Isabelle Mansuy
Glutamate Uptake in Synaptic Plasticity: From
Mollusc to Mammal Pp.593-603
Jonathan
M. Levenson, Edwin J. Weeber, J. David Sweatt and
LTP, Memory and Structural Plasticity Pp.605-611
Dominique
Muller, Irina Nikonenko, Pascal Jourdain and Stefano Alberi
Gene Control of Synaptic Plasticity and
Memory Formation: Implications for Diseases and Therapeutic Strategies Pp.613-628
Cyrille
Vaillend, Claire Rampon, Sabrina Davis and Serge Laroche
Stress, Metaplasticity, and Antidepressants Pp.629-638
René
Garcia
A Comparative Review of Rodent Prefrontal
Cortex and Working Memory
Pp.639-647
Matthew
W. Jones
Cellular Mechanisms of Striatum-Dependent
Behavioral Plasticity and Drug Addiction Pp.649-665
Stephania
Fasano and Riccardo Brambilla
Synaptic Plasticity in Drug Reward Circuitry Pp.667-676
Danny
G. Winder, Regula E. Egli, Nicole L. Schramm and Robert T. Matthews
[Back to top] Glutamate Uptake in Synaptic Plasticity: From
Mollusc to Mammal
Jonathan
M. Levenson, Edwin J. Weeber, J. David Sweatt and
A great deal of
research has been directed toward understanding the cellular mechanisms
underlying synaptic plasticity and memory formation. To this point, most
research has focused on the more “active” components of synaptic
transmission: presynaptic transmitter release and postsynaptic transmitter
receptors. Little work has been done characterizing the role neurotransmitter
transporters might play during changes in synaptic efficacy. We review several
new experiments that demonstrate glutamate transporters are regulated during
changes in the efficacy of glutamatergic synapses. This regulation occurred
during long-term facilitation of the sensorimotor synapse of Aplysia and
long-term potentiation of the Schaffer-collateral synapse of the rat. We
propose that glutamate transporters are “co-regulated” with other
molecules/processes involved in synaptic plasticity, and that this process is
phylogenetically conserved. These new findings indicate that glutamate
transporters most likely play a more active role in neurotransmission than
previously believed.
[Back to top] LTP, Memory and Structural Plasticity
Dominique
Muller, Irina Nikonenko, Pascal Jourdain and Stefano Alberi
Our current
understanding of the mechanisms of information processing and storage in the
brain, based on the concept proposed more than fifty years ago by D. Hebb, is
that a key role is played by changes in synaptic efficacy induced by coincident
pre- and postsynaptic activity. Decades of studies of the properties of
long-term potentiation (LTP) have shown that this form of plasticity adequately
fulfills these requirements and is likely to contribute to several models of
learning and memory. Recent analyses of the molecular events implicated in LTP
are consistent with the view that modifications of receptor properties or
insertion of new receptors account for the potentiation of synaptic
transmission. These experiments, however, have also uncovered an unexpected
structural plasticity of synapses. Dendritic spines appear to be dynamic
structures that can be formed, modified in their shape or eliminated under the
influence of activity. Furthermore, recent studies suggest that LTP, in
addition to changes in synaptic function, is also associated with mechanisms of
synaptogenesis. We review here the evidence pointing to this activity-dependent
remodeling and discuss the possible role of this structural plasticity for
synaptic potentiation, learning and memory.
[Back to top] Gene Control of Synaptic Plasticity and
Memory Formation: Implications for Diseases and Therapeutic Strategies
Cyrille
Vaillend, Claire Rampon, Sabrina Davis and Serge Laroche
There has been
nearly a century of interest in the idea that information is stored in the
brain as changes in the efficacy of synaptic connections between neurons that
are activated during learning. The discovery and detailed report of the
phenomenon generally known as long-term potentiation opened a new chapter in
the study of synaptic plasticity in the vertebrate brain, and this form of
synaptic plasticity has now become the dominant model in the search for the
cellular and molecular bases of learning and memory. Accumulating evidence
suggests that the rapid activation of the genetic machinery is a key mechanism
underlying the enduring modification of neural networks required for the laying
down of memory. Here we briefly review these mechanisms and illustrate with a
few examples of animal models of neurological disorders how new knowledge about
these mechanisms can provide valuable insights into identifying the mechanisms
that go awry when memory is deficient, and how, in turn, characterisation of
the dysfunctional mechanisms offers prospects to design and evaluate molecular
and biobehavioural strategies for therapeutic prevention and rescue.
[Back to top] Stress, Metaplasticity, and Antidepressants
René
Garcia
A large body of evidence
has established a link between stressful life events and development or
exacerbation of depression. At the cellular level, evidence has emerged
indicating neuronal atrophy and cell loss in response to stress and in
depression. At the molecular level, it has been suggested that these cellular
deficiencies, mostly detected in the hippocampus, result from a decrease in the
expression of brain-derived neurotrophic factor (BDNF) associated with
elevation of glucocorticoids. Thus, an increase in expression of BDNF,
facilitating both neuronal survival and neurogenesis, is thought to represent a
converging mechanism of action of various types of antidepressant treatments
(e.g., antidepressant drugs and transcranial magnetic stimulation). However, as
also revealed by converging lines of evidence, high levels of glucocorticoids
down-regulate hippocampal synaptic connectivity (‘negative’
metaplasticity), whereas an increase in expression of BDNF up-regulates
connectivity in the hippocampus (‘positive’ metaplasticity).
Therefore, antidepressant treatments might not only restore cell density but
also regulate higher-order synaptic plasticity in the hippocampus by abolishing
‘negative’ metaplasticity, and thus restore hippocampal cognitive
processes that are altered by stress and in depressed patients. This
antidepressant regulatory effect on hippocampal synaptic plasticity function,
which may, in turn, suppress ‘negative’ metaplasticity in other
limbic structures, is discussed.
[Back to top] A Comparative Review of Rodent Prefrontal Cortex and Working Memory
Matthew W. Jones
The prefrontal
cortex is critical to working memory processes. Current theories of prefrontal
function are largely based on primate behavioural and electrophysiological
data. As molecular genetic techniques advance in mice, so investigations into
the rodent prefrontal cortex should expand, such that rodent models of
prefrontal function during working memory may be used to study the synaptic and
molecular basis of the phenomenon. This review attempts to summarize aspects of
published data that pertain to working memory and suggest directions that will
allow a coherent comparison of prefrontal function and interaction in monkey,
rat and mouse.
[Back to top] Cellular Mechanisms of Striatum-Dependent Behavioral Plasticity and
Drug Addiction
Stephania
Fasano and Riccardo Brambilla
The striatum has
long been known to be involved in the control of motor behavior, since
disruption of dopamine-mediated function in this brain structure is directly
linked to Parkinson’s disease and other disorders of movement. However,
it is now accepted that both dorsal and ventral striatal nuclei are also
essential for a variety of cognitive processes, which depend on reward-based
stimulus-response learning. Since the neuroanatomical and neurochemical
organization of dorsal and ventral striatum is only partially overlapping, it
is likely that both common and nucleus-specific cellular and molecular events
contribute to synaptic plasticity, learning and memory processes mediated by
these cerebral structures. Alterations in cell signaling in the striatum may be
particularly important in the response to both acute and chronic administration
of drugs of abuse, resulting in maladaptive changes in the reward-based
associative learning involved in addiction, withdrawal and relapse.
[Back to top] Synaptic Plasticity in Drug Reward Circuitry
Danny
G. Winder, Regula E. Egli, Nicole L. Schramm and Robert T. Matthews
Drug addiction is
a major public health issue worldwide. The persistence of drug craving coupled
with the known recruitment of learning and memory centers in the brain has led
investigators to hypothesize that the alterations in glutamatergic synaptic
efficacy brought on by synaptic plasticity may play key roles in the addiction
process. Here we review the present literature, examining the properties of
synaptic plasticity within drug reward circuitry, and the effects that drugs of
abuse have on these forms of plasticity. Interestingly, multiple forms of
synaptic plasticity can be induced at glutamatergic synapses within the dorsal
striatum, its ventral extension the nucleus accumbens, and the ventral
tegmental area, and at least some of these forms of plasticity are regulated by
behaviorally meaningful administration of cocaine and/or amphetamine. Thus, the
present data suggest that regulation of synaptic plasticity in reward circuits
is a tractable candidate mechanism underlying aspects of addiction.