Tackling neurotransmission precision

From Human Ethology listserv. This is an excellent example of proper reductionism, IMO.

To see the pictures, click the URL at the bottom of the message.




[ Tackling

neurotransmission precision ](https://groups.yahoo.com/neo/groups/human-ethology/conversations/topics/63849;_ylc=X3oDMTJzMWpzYmoxBF9TAzk3MzU5NzE1BGdycElkAzE5NDU5MzAzBGdycHNwSWQDMTcwNTA4MzEyNQRtc2dJZAM2Mzg0OQRzZWMDZG1zZwRzbGsDdm1zZwRzdGltZQMxNDE5MjQ5MDAy)

Sun Dec 21, 2014 6:49 am (PST) . Posted by:

“Jay Feierman”


Tackling neurotransmission precision
December 18th, 2014 in Neuroscience

Freeze fracture replica image showing the voltage-gated calcium channels
clusters on presynaptic membrane in rats. The green circles represent
channel clusters, and inside each green circle are small black dots, which
are the individual channels. This is easier to see in the inset, labeled
A3, where the channels are blue dots. Credit: Professor Tomoyuki Takahashi

Behind all motor, sensory and memory functions, calcium ions are in the
brain, making those functions possible. Yet neuroscientists do not entirely
understand how fast calcium ions reach their targets inside neurons, and
how that timing changes neural signaling. Researchers at the Okinawa
Institute of Science and Technology Graduate University have determined how
the distance from calcium channels to calcium sensors on vesicles affects a
neuron’s signaling precision and efficacy.

In international collaboration with research institutes such as the Pasteur
Institute and the Institute of Science and Technology Austria, Professor
Tomoyuki Takahashi and the Cellular and Molecular Synaptic Function Unit
described the locations of voltage-gated calcium channels, which allow
calcium ions to enter into the neuron, triggering vesicles to release
neurotransmitters, signaling to the next neuron. This research, to be
published the January 7, 2015 issue of Neuron, illuminates decades of
mystery behind the precision and efficacy of neurotransmitter release,
suggesting how signaling changes as an animal matures.

After an electrical spike, or an instantaneous change in voltage, travels
through the neuron, it reaches the presynaptic terminal. The presynaptic
terminal is an area facing the synaptic cleft, or the gap between one
neuron and the next. The electrical spike triggers voltage-gated calcium
channels to open, allowing calcium ions to enter the presynaptic terminal.
The calcium ions then diffuse locally around the channels and encounter
synaptic vesicles, small packages of neurotransmitters, which are signaling
molecules. The calcium ions interact with sensor proteins on the vesicle,
triggering the vesicles to fuse with the presynaptic terminal membrane, and
releasing neurotransmitters into the synaptic cleft toward the next neuron.

Yet researchers have never fully grasped how calcium travels from gated
channel to vesicle. Some researchers argued that the channels were spread
across the active zone of the presynaptic terminal, while others argued
that a ring of gated channels surrounded each vesicle. Therefore,
Takahashi’s project began with an electron microscope technique, where the
researchers froze the presynaptic membrane and broke it open to expose the
calcium channels. They found that the channels existed in clusters, with a
variable number of channels in each cluster.

Next, the researchers ran various tests and simulations to determine how
the channel clusters impact signaling. They found that clusters with more
calcium channels more effectively trigger a nearby vesicle to release
neurotransmitters. Importantly, channel clusters closer to vesicles trigger
neurotransmitter release more quickly and more efficiently than clusters
located farther from vesicles, increasing signal precision. “The calcium
sensor on vesicles need a high concentration of calcium to trigger vesicle
release,” Takahashi said. “If the calcium entered from farther away, then
it would diffuse into a lower concentration or bind to other proteins
before reaching the calcium sensor on the vesicle.”

New model that Professor Takahashi and his collaborators have proposed.
Circles are vesicles filled with blue neurotransmitters, and the smaller
grey circles are voltage-gated channels. Instead of measuring from the
vesicle to the center of the channel cluster (green line), Takahashi
suggests measuring to the perimeter of the channel cluster (red line). The
difference is that measuring to the center varies with the size of the
cluster, whereas measuring to the perimeter will always describe the
closest channel to the vesicle Credit: OIST
Takahashi and his collaborators also studied how the distance changes as
their rat subjects developed, and how the distance changes affect neural
signaling. As the rat aged from seven days to fourteen days, the distance
between the gated channels and the vesicle shrank from 30 nanometers to 20
nanometers. “This maturation is fairly significant,” Takahashi said,
explaining that the vesicles release much more quickly after calcium enters
the synapse. “The signal becomes 30% faster,” he said.

Moving forward, Takahashi and his collaborators propose the perimeter
release model for use in neuroscience research. This model establishes that
calcium channels exist in clusters and that the distance from these
clusters to a vesicle is significant. “If you measure the distance from the
center of the cluster, then this distance depends on the size of the
cluster,” Takahashi said. Therefore, the researchers propose the distance
from vesicle to gated channel clusters be measured from the perimeter of
the cluster, rather than the center. Distances calculated using this new
model can explain how signaling precision increases during development.

“If there is anything which widens this distance,” Takahashi said, “it
actually interferes with neural precision and it can interfere with memory

Provided by Okinawa Institute of Science and Technology

“Tackling neurotransmission precision.” December 18th, 2014.

The dinosaurs never saw that asteroid coming. What’s* ourexcuse?**
~~ Neil deGrasse Tyson*