1198 VOLUME 18 | NUMBER 9 | SEPTEMBER 2015 NATURE NEUROSCIENCE
NEWS AND VIEWS
The interpretation of the study by Guo et al.
4
also opens an interesting debate on the complex
relationship between structural spine changes
and functional plasticity, in the form of LTP. In
fact, the authors hypothesize that spines repre-
sent a substrate for structural plasticity that does
not necessarily correlate with functional plas-
ticity. Indeed, the loss of LTP associated with
lack of endogenous dopamine was not directly
related to the observed structural spine changes.
Conversely, the authors attribute to LTP the
ability to stabilize newly formed spines.
The analysis of dynamic changes of spine
morphology could have implications not only
for the pathophysiology of PD, but also for
the motor and behavioral side effects related
to dopamine replacement therapy of this neu-
rodegenerative disorder. After a few years of
treatment, l-DOPA causes a series of hyper-
kinetic motor symptoms called l-DOPA–
induced dyskinesias that limit the use of this
therapy. These dyskinesias are thought to be
caused by loss of LTP reversal at cortico-striatal
synapses
7
. This latter event, also referred to
as depotentiation, is usually induced by low-
frequency stimulation (1–2 Hz). It represents
the ability of an already potentiated synapse to
return to control levels and allows the erasure
of unessential memory information.
Nevertheless, alterations in spine dynam-
ics at the level of motor cortex could just as
well contribute to this disabling phenom-
enon. Similarly, aberrant plasticity at cortical
synapses may be responsible for the impulse
control disorders observed during dopamin-
ergic treatment. Impulse control disorders,
including compulsive gambling, buying,
sexual behavior and eating, are increasingly
recognized as serious psychiatric complica-
tions in PD
8
, and they may be the result of an
anomalous interaction between dopamine and
glutamate at the level of the cortical spines.
From the clinical point of view, three main
aspects should be considered in the interpreta-
tion of most of the data resulting from PD ani-
mal models, including the study by Guo et al.
4
.
First, PD is a slow neurodegenerative disorder
in which dopaminergic denervation occurs over
decades. By contrast, dopaminergic denervation
is induced in most preclinical studies by acute
neurotoxic lesions. Structural plasticity may dif-
fer in these two situations. Second, aging is the
greatest risk factor for the development of PD, as
well as other neurodegenerative disorders
9
. Yet
most experimental studies, including that of Guo
et al.
4
, use young animals, in which plastic events
may not be influenced by the different molecular
environment that characterizes the aging brain
Third, PD is more than just dopamine loss
10
.
The widespread, multisystem nature of the neu-
rodegeneration that characterizes PD leads to
the involvement of different neurotransmitters,
including acetylcholine, serotonin and nora-
drenaline
11
, whose modulation could act in
concert with dopamine loss to influence both
structural and functional plasticity.
Nevertheless, imaging of spine turnover
coupled to electrophysiological analyses of
synaptic plasticity and behavioral investigation
represents a powerful approach to clarifying the
role of the cortex in neurotransmitter-related
disorders. Future studies implementing a simi-
lar approach in the deeper basal ganglia nuclei
might allow the precise description of an inte-
grative model of motor control and subcellular
mechanisms underlying movement disorders.
COMPETING FINANCIAL INTERESTS
The authors declare no competing financial interests.
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Bhatia, K. Lancet 384, 523–531 (2014).
2. Calabresi, P., Picconi, B., Tozzi, A., Ghiglieri, V. &
Di Filippo, M. Nat. Neurosci. 17, 1022–1030 (2014).
3. Day, M. et al. Nat. Neurosci. 9, 251–259 (2006).
4. Guo, L. et al. Nat. Neurosci. 18, 1299–1309 (2015).
5. Yagishita, S. et al. Science 345, 1616–1620 (2014).
6. Ueno, T. et al. Neurobiol. Dis. 64, 142–149 (2014).
7. Calabresi, P., Ghiglieri, V., Mazzocchetti, P., Corbelli, I.,
Picconi, B. Levodopa-induced plasticity: a double-
edged sword in Parkinson’s disease? Philos. Trans.
R. Soc. Lond. B Biol. Sci. 370, 20140184 (2015).
8. Weintraub, D., David, A.S., Evans, A.H., Grant, J.E. &
Stacy, M. Mov. Disord. 30, 121–127 (2015).
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Neurosci. 12, 359–366 (2011).
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11. Hall, H. et al. Brain 137, 2493–2508 (2014).
Character studies
Ming Hsu & Adrianna C Jenkins
How do individuals attribute dispositional properties, or traits, to others? A study suggests that associative learning
processes underlie aspects of trait learning at both neural and behavioral levels.
Ming Hsu and Adrianna C. Jenkins are in the Haas
School of Business and Helen Wills Neuroscience
Institute, University of California, Berkeley,
Berkeley, California, USA.
e-mail: mhsu@haas.berkeley.edu
In O. Henry’s “The Gift of the Magi ”, a young
wife sells her prized hair to buy her husband a
chain for his gold watch, while the husband sells
the watch to buy her expensive combs. Thus,
unbeknownst to the other, each is left with a
gift that neither can use. One possible takeaway
is that the gifts failed miserably and that the
couple should have consulted each other before
their purchases. But most of us focus instead on
the husband and wife’s generous dispositions.
Beginning with Heider
1
, how perceivers attri-
bute dispositional properties, or traits, to others
has been among the most enduring questions
in psychology
2
. In recent years, there has been
increasing interest in approaching this ques-
tion using cognitive neuroscience techniques.
However, despite important advances
3
, we
remain far from a mechanistic understanding of
how particular brain regions enable trait infer-
ence, particularly regarding the computations
essential to binding high-level theories of social
cognition to the underlying neurobiology.
In a functional magnetic resonance imaging
(fMRI) study reported in this issue of Nature
Neuroscience, Hackel, Doll and Amodio
4
take
an important step in this direction. Using an
innovative combination of ideas and tools
from social psychology, economics and cog-
nitive neuroscience, they offer neural evi-
dence that associative learning processes are
involved in making inferences about traits.
Specifically, the authors conducted a study in
which participants interacted repeatedly with
eight different partners: four purported human
participants and four slot machines. On each
trial, participants chose to interact with one
of two human (or slot machine) counterparts.
The chosen counterpart, who had been
endowed with a certain number of points on
that trial, then shared some proportion of
those points with the participant. Critically,
targets varied orthogonally in terms of the
average magnitude of their starting endow-
ment (reward) and the average proportion of
the endowment that was shared with the par-
ticipant (generosity), enabling the authors to
dissociate signals associated with trait learning
from those associated with reward processing.
Consistent with the idea that trait learning
engages associative learning processes, BOLD
(blood oxygen level-dependent) responses of the
npg
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