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|
Name |
Email |
Telephone |
| Professor |
OGURA,
Akihiko |
 |
+81-6-6850-5426 |
| Associate Prof. |
TOMINAGA-YOSHINO, Keiko |
 |
+81-6-6850-5428 |
| Assistant Prof. |
SHINODA, Yo |
 |
+81-6-6850-5427 |
| COE Assistant Prof. |
Taniguchi, Naoko |
 |
+81-6-6850-5428 |
One of the most typical functions of
the brain is memory. Some 20 years ago, memory was a theme
in the field of psychology. But it is now in the field of
biology. Brain functions are realized by the activity of
neuronal networks composed of a huge number of neurons. The
efficiency of information transfer within the networks is
changeable. Even the networks themselves can change by
experience. Information transfer between neurons is performed
at synapse, the site of neurons' contact, by releasing
information molecule (=neurotransmitter) from pre-synaptic
cell and capturing it by post-synaptic cell. The amount of
released neurotransmitter or the efficacy of capture can
change. Moreover, synapses are found to be newly formed upon
activity or abandoned upon inactivity. These changes are
called "synaptic plasticity". Thus, the fundamental process
of brain memory can be analyzed biologically in the questions
such as: how does the release of neurotransmitter increase;
how do the terminals of neurons bud out. Memory is classified
into a short-term one, quickly formed but short-living, and
a long-term one, slowly formed but long-living. Biologically,
the former corresponds to a short-term plasticity, the process
occurring in existing synapse with no need of protein synthesis,
and the latter to a long-term plasticity, the process accompanied
by new synapse formation (=synaptogenesis) and protein synthesis.
The former was profoundly analyzed after the discovery of excellent
model systems for analysis such as "sensitization of gill withdrawal
response in Aplysia (=a sea slug)" or "posttetanic potentiation
in hippocampus (=a part of cerebral cortex)". The year 2000's
Nobel Prize for Medicine was awarded to Dr. Eric Kandel for
his study on Aplysia. I (Ogura) was once engaged in the study
of posttetanic potentiation and made a small contribution to
it. In contrast, the long-term plasticity remains still nearly
unexplored. It is mainly because of the absence of a good model
system for analysis. Once it is established, the biologists
of the world can concentrate their efforts into that and the
mechanism should be revealed, as was the case in the short-term
plasticity. We are challenging this issue.
|
Fig.1 Scanning electron micrograph of
a cultured hippocampal neuron growing on a glial cell |
 |
|
Fig.2 Hippocampal slice cultured for
14 days |
 |
| 1 |
Activity-induced synapse
formation |
| Brain slices prepared from newborn rat pups
can be maintained for months, if oxygen and nutrition
are properly supplied. This "cultured brain slice" is
amenable to the long-term microscopic observation of
ongoing processes, to drug application, or to gene
manipulation. It is a good candidate for the wanted
model system. We recently found that repetitive stimulation
leads to synaptic reinforcement accompanied by synaptogenesis.
Single, however strong, stimulation was not enough.
Three repetitions, with a proper interval, were needed.
We are now intriguing what different cellular events
follow after the 1st and 3rd stimulations, what processes
occur in the interval periods, etc. |
|
Fig.3 Growing tip of a neuron in a cultured
hippocampal slice after stimulation |
 |
|
Fig.4 Electron micrograph
of a cultured slice with synapses bifurcating after
stimulation |
 |
| 2 |
Inactivity-induced synapse
elimination and neuronal death |
| Neurons isolated from newborn rat's cerebellum
cannot be maintained long, unless stimulant (=potassium
chloride or glutamic acid) was added to the culture
medium. This activity-dependent survival or inactivity-induced
apoptosis (=cell death) had been thought that an elevation
of intracellular Ca2+ level above a certain limit due
to an enhanced Ca2+ inflow guarantees the survival
(by blocking apoptotic signal cascades). But direct
measurements of Ca2+ done by us did not show the difference
in cytoplasmic Ca2+. Enhanced Ca2+ inflow was counterbalanced
by enhanced Ca2+ pumping. What differed between surviving
and dying neurons were local Ca2+ turnover and exo/endocytotic
behavior. Probably some neurotrophic (=survival promoting)
substance is released and incorporated. We further
hypothesize that the death of a whole cell may share
a common mechanism with the death of an individual
synapse. |
| 3 |
Physiology of glial
cells |
| The brain is composed not only of nerve
cells but also of glial cells. Glial cells have long
been regarded as physiologically dull cells, such like
a mere structural support or a housekeeper. Recently,
however, they are found to exert important functions
such as the synthesis of neurotrophic substances. They
transmit signals between them quite similarly to neurons
(although slow). We like to cast new light to glial
cell functions. |
 |
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