A new method
for imaging brain activity
Neuronal mitochondria give
high resolution images of neuronal activity
patterns
September 21, 2007. A picture
is worth a thousand single-units. Understanding
the details of brain activity has, for nearly
50 years, relied predominantly on recording
electrical activity from one or a few neurons
at a time. Over the last 20 years, however,
methods for imaging brain activity patterns
have become progressively better at revealing
the fine nuances of neural processing.
A new study from the Issa lab in the August 8th issue
of the Journal of Neuroscience takes brain imaging
to a new level. Husson et al. report a method
for imaging brain activity in large mammals
with high resolution and without the need for
extrinsic dyes.
The method, flavoprotein autofluorescence
imaging, relies on proteins in neuronal mitochondria
that fluoresce in response to increased energy
demand, such as during the firing of action
potentials. The mitochondrial location of the
fluorophore conveys several advantages, among
them a theoretical sub-cellular spatial resolution
and specificity to neurons rather than glia.
The authors show that this mitochondrial
signal is preferable in several ways to standard
imaging techniques that rely on blood flow and
blood oxygenation (BOLD signal). Specifically,
compared to the current gold standard in high-resolution
functional imaging (intrinsic signal imaging),
autofluorescence has better temporal and spatial
resolution, substantially reduced vascular artifacts,
and reduced need for image filtering.
While autofluorescence has been
recently used to image rodent brains, work by
other groups suggested it couldn't be applied
to larger brains - precluding its use in humans.
The new research, funded by the Brain Research
Foundation and the Mallinckrodt Foundation,
suggests that the technique holds promise for
high-resolution human brain imaging. Because
there is no need for dyes or other extraneous
compounds, there is no risk for toxic reactions
during imaging. As a result, it has potential
as a diagnostic tool for both functional disorders
of the brain as well as for identification of
pathological tissue without resection.
More Information:
Husson, T., Mallik, A.K.,
Zhang, J., Issa, N.P. Functional Imaging of
Primary Visual Cortex Using Flavoprotein Autofluorescence.
J. Neurosci. 2007, 27:8665-8675.
The
Issa Lab Website
The
Brain Research Foundation
Neuronal differentiation
in the development of motor circuits
Notch1 signaling regulates
interneuron diversity
March 15, 2007. Why do
some neurons in the spinal cord come to control
breathing and others take on different functions?
New research from Dr. Kamal Sharma's
lab, published in the March 15th issue of Neuron,
shows that a specific set of receptors determines
how neuronal stem cells take on new fates as
spinal interneurons - the type of neuron that
facilitates local communication within the spinal
cord.
The reasearch, funded by the Brain
Research Foundation, the March of Dimes and
the National Institutes of Health, has important
implications for one of the most basic physiological
functions, since one of the interneurons studied
is crucial to regulating breathing in mammals.
A hallmark of the adult nervous
system is the diversity of neurons. Each neuron
type performs a specific function. The main
challenge for the developing nervous system
is to ensure that each neuron type is generated
at the right time and acquires properties that
it would use to perform essential functions
in the adult.
In the embryonic nervous system
three mechanisms are used to generate neuronal
diversity. These include secreted morphogens,
transcription factors and cell-cell interactions.
In this study Chian-Yu Peng and colleagues show
how cell-cell interactions mediated by the Notch1
receptor and one of its partners, Delta4, help
in the generation of two distinct interneurons
from progenitor cells that are identical.
This novel mechanism is used to
generate excitatory interneurons called V2aIN
and inhibitory interneurons called V2bIN. Dr.
Sharma, the senior author in this study, thinks
that the development of these neurons has important
functional consequences. Recent studies in his
laboratory, conducted in collaboration with
Dr. Jan-Marino Ramirez, also at the University
of Chicago. Have found that V2aIN neurons have
a critical role in the regulation of breathing.
More Information:
Peng
et al. Notch and MAML Signaling Drives
Scl-Dependent Interneuron Diversity in the
Spinal Cord. Neuron, Vol 53, 813-827,
15 March 2007
The Sharma Lab Website
The
Brain Research Foundation
The
March of Dimes
The
National Institutes of Health
Bacterial infections in the lungs
of cystic fibrosis patients can cause chronic
inflammation, which in turn induces tissue damage
and worsens the symptoms of the disease. One way
that cells clear bacterial infection is through
phagocytosis - where specialized cells, called
macrophages, ingest the bacteria and destroy them
by digestion in acidic compartments.
The authors found that CFTR, a chloride
ion channel, is present in particular macrophage
cells that function specifically in the lung.
Using macrophages obtained from mice that are
genetically engineered to no longer express the
CFTR protein, or by specifically inhibiting CFTR,
the authors show that there is a defect in acidification
of the digestive compartment in the cell. As a
result, an alkaline environment persists, permitting
bacterial growth and division.
Macrophages are a key player in
the body's defence mechanism. Compromising their
function, as shown by Nelson and colleagues, may
begin to explain the persistent infections observed
in cystic fibrosis patients.
CFTR regulates phagosome acidification
in macrophages and alters bactericidal activity
Anke Di, Mary E. Brown, Ludmila
V. Deriy, Chunying Li, Frances L. Szeto, Yimei
Chen, Ping Huang, Jiankun Tong, Anjaparavanda
P. Naren, Vytautas Bindokas, H. Clive Palfrey
& Deborah J. Nelson
Published online: 20 August 2006
| doi:10.1038/ncb1456 Abstract
| Full
text
