Activity-Dependent Regulation of a
Chloride Transporter
Claudio Rivera, Juha Voipio, Judith Thomas-Crusells,
Hong Li, Zsuzsa Emri, Sampsa Sipilä, John A. Payne, Liliana
Minichiello, Mart Saarma, and Kai Kaila
The chloride conductance of GABAA receptors
usually hyperpolarizes cells because
of the tireless activity of the K–Cl
cotransporter, KCC2, which keeps intracellular
chloride low. In the absence of cotransporter
activity, GABAA responses become175
depolarizing, as occurs in hippocampal
neurons under conditions of intense stimulation.
NowRivera et al. present a molecular
explanation for rapid activity-dependent
shifts in the chloride gradient. After
interictal-like activity in the hippocampus,
they observed downregulation of KCC2
mRNA and protein that resulted from endogenous
BDNF binding at TrkB receptors.
Using transgenic mice with mutations to the
phospholipase C docking site and the Shc
binding site, they determined that both of
these signaling pathways were activated.
Given the rapid turnover rate ofmembranebound
KCC2, downregulation of the transporter
may act as a dynamic mechanism for
regulation of neuronal excitability.
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Neurotrophin Receptors and
Motoneuron Survival In Vivo
Thomas W. Gould and Ronald W.
Oppenheim
Approximately 50% of motoneurons (MNs) die during development.
This programmed cell death (PCD) culls~50% of the neurons
because they apparently fail to compete for a limited supply
of musclederived neurotrophic factors (NTFs). The question
is which growth factor (and which of the growth factor receptors)
is expressed on
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motoneurons or closely associated Schwann cells. To address
this issue, Gould and Oppenheim examined the specific pool
of MNs that innervates a pair of thigh adductor muscles in
chick embryos. They examined expression of seven growth factors
and their cognate receptors. Neurons within the adductor pool
homogeneously expressed a set of growth factor receptors.
Furthermore, combined treatment with BDNF, GDNF, CNTF, and
HGF was required to completely prevent PCD. The authors also
provide evidence of rescue in trans from other motoneurons.
The results underscore the complexity of signals that mediate
the life and death struggle of developing motoneurons.
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the full article
Sleeplessness and Task Complexity
Michael W. L. Chee and Wei Chieh
Choo
Even a single night without sleep dulls our
mental performance. Seems obvious,
right? Well, what’s less obvious is that
complex task performance is better preserved
after sleep deprivation than simple
tasks. In this issue, Chee and Choo use
functional magnetic resonance imaging to
examine brain activity after 24 hr without
sleep to probe the regions responsible for
this task dependence. Not surprisingly,
sleep deprivation slowed the subjects’ responses
to tasks requiring either maintenance
or manipulation and maintenance
of memory. Both tasks activated bilateral,
left hemisphere-dominant frontoparietal
areas, as expected for verbal working
memory tasks. After sleep deprivation,
some brain areas showed reduced activation
(medial parietal), and others showed
reduced deactivation (anterior medial
frontal and posterior cingulate). In addition,
increased activation was apparent in
the left dorsolateral prefrontal cortex and
thalamus, which the authors suggest represents
compensatory activity required
for complex task performance.
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article
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Pyramidal Cell Activity in APP-Sw
Mice
Edward A. Stern, Brian J. Bacskai,
Gregory A. Hickey, Frank J. Attenello,
Julianne A. Lombardo, and Bradley T.
Hyman
A number of studies suggest that the accumulation
of amyloid-ßpeptide in plaques in Alzheimer’s disease
(AD) can affect the cellular and synaptic properties of neurons
as well as the circuitry of neuronal networks. Stern et al.
approached this issue by recording in vivo from neocortical
pyramidal neurons in one of the most commonly used animal
models of AD, APP-Sw mice that overexpress the amyloid precursor
protein (APP). They examined mice at two stages, 8–9 months,
when there is soluble amyloid accumulation but no plaques,
and 14 months, when there is significant plaque formation.
As amyloid-_ plaques accumulated, neuronal processes coursing
in the vicinity were distorted, but the overall level of synaptic
activity was similar to control animals. However transcallosal
stimulation revealed considerably more variability in responses
in the AD mice, suggesting that temporal synchrony was reduced.
The authors suggest that the effect of amyloid-ß on
synaptic transmission in these mice involves disruption of
the normal networks, in part because of the distortion of
neurites by plaques.
Image of neurites deflecting around an amyloid-ß
plaque that is labeled in yellow with thioflavine-2. Scale
bar, 20 µm. See the article by Stern et al. for details.
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the full article
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