And who is going to translate this into a stroke protocol? [crickets]
ASA, NSA, WSO? You don't think your doctor along with the thousands of
other neurologists is going to have the ability to do this by
themselves?
http://www.alphagalileo.org/ViewItem.aspx?ItemId=132072&CultureCode=en
Max Planck scientists in Göttingen have discovered a key mechanism that boosts the signalling function of neurons in the brain
Locating a car that’s blowing its horn in heavy traffic,
channel-hopping between football and a thriller on TV without losing the
plot, and not forgetting the start of a sentence by the time we have
read to the end – we consider all of these to be normal everyday
functions. They enable us to react to fast-changing circumstances and to
carry out even complex activities correctly. For this to work, the
neuron circuits in our brain have to be very flexible. Scientists
working under the leadership of neurobiologists Nils Brose and Erwin
Neher at the Max Planck Institutes of Experimental Medicine and
Biophysical Chemistry in Göttingen have now discovered an important
molecular mechanism that turns neurons into true masters of adaptation.
Neurons communicate with each other by means of specialised
cell-to-cell contacts called synapses. First, an emitting neuron is
excited and discharges chemical messengers known as neurotransmitters.
These signal molecules then reach the receiving cell and influence its
activation state. The transmitter discharge process is highly complex
and strongly regulated. Its protagonists are synaptic vesicles, small
blisters surrounded by a membrane, which are loaded with
neurotransmitters and release them by fusing with the cell membrane. In
order to be able to respond to stimulation at any time by releasing
transmitters, a neuron must have a certain amount of vesicles ready to
go at each of its synapses. Brose has been studying the molecular
foundations of this stockpiling for years.
The problem is not merely academic. “The number of immediately
releasable vesicles at a synapse determines its reliability,” explains
Brose. “If there are too few and they are replenished too slowly, the
corresponding synapse becomes tired very quickly in conditions of
repeated activation. The opposite applies when a synapse can quickly top
up its immediately available vesicles under pressure. In fact, such a
synapse may even improve with constant activation.”
This synaptic adaptability can be observed in practically all
neurons. It is known as short-term plasticity and is indispensable for a
large number of extremely important brain processes. Without it, we
would not be able to localise sounds, mental maths would be impossible,
and the speed and flexibility with which we can alter our behaviour and
turn our attention to new goals would be lost.
Some years ago, Brose and his team discovered a protein with the
cryptic name of Munc13. Not only is this protein indispensable for the
replenishment of vesicles for immediate release at synapses; neuron
activity regulates it in such a way that the fresh supply of vesicles
can be adjusted in line with demand. This regulation occurs by means of a
complex consisting of the signal protein calmodulin and calcium ions
that build up in the synapses during intense neuron activity.
“Our earlier work on individual neurons in culture dishes showed that
the calcium-calmodulin complex activates Munc13 and consequently
ensures that immediately releasable vesicles are replenished faster,”
says Noa Lipstein, an Israeli guest scientist in Brose’s lab. “But many
colleagues were not convinced that this process also played a role in
neurons in the intact brain.”
So Lipstein and her Japanese colleague Takeshi Sakaba created a
mutant mouse with genetically altered Munc13 proteins that could not be
activated by calcium-calmodulin complexes. The two neurophysiologists
first studied the effects of this genetic manipulation on synapses
involved in the localisation of sound, which are typically activated
several hundred times every second. “Our study shows that the sustained
efficiency of synapses in intact neuron networks is critically dependent
on the activation of Munc13 by calcium-calmodulin complexes,” explains
Lipstein.
The Göttingen-based scientists are convinced of the significance of
their study. After all, leading neuroscientists of the past described
the calcium sensor responsible for synaptic short-term plasticity and
its target protein as the Holy Grail. “I am confident that we have
discovered a key molecular mechanism of short-term plasticity that plays
a role in all synapses in the brain, and not only in cultivated
neurons, as many colleagues believed,” affirms Lipstein. And if she is,
in fact, proved right about the interpretation of her findings, Munc13
could even be an ideal pharmacological target for drugs that influence
brain function.
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